| Title of Invention | NEW INDOLE DERIVATIVES AS FACTOR XA INHIBITORS |
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| Abstract | The present invention relates to compounds of the formula (I), in which R<sup>0</sup> R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>; Q; V, G and M have the meanings indicated in the claims. The compounds of the formula (I) are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (Fxa) and/or factor VIla (FVIla), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIla is present or for the cure or prevention of which an inhibition of factor Xa and lor factor VIla is intended. The invention furthermore relates to processes for the preparation of compounds of formula (I), their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them. |
| Full Text | in which R*'; R""; R1; R1; R'*; R1; RS; R1; Q; V, Gand M have the meanings indicated below. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and 10 prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood dotting enzymes factor Xa (FXa) and/or factor Vila (FVIIa). and can in general be applied in conditions in which an undesired activity of faaor Xa and/or factor Vila is present or for the cure or prevention of which an inhibition of factor Xa and/or factor Vila is Intended. The invention furthermore relates to processes for the preparation of 15 compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them. Normal haemeostasis is the result of a complex balance between the processes of clot initiation, formation and clot dissolution. The complex interactions between blood ceils, 20 specific plasma proteins and the vascular surface, maintain the fluidity of blood unless injury and blood loss occurs (EP-A-987274). Many significant disease states are related to abnormal haemeostasis. For example, local thrombus formation due to rupture of atheroslerotic plaque is a major cause of acute myocardial infarction and unstable angina. Treatment of an occlusive coronary thrombus by either thrombolytic therapy or percutaneous angioplasty may be 25 accompanied by acute thrombolytic reclosure of the affected vessel. There continues to be a need for safe and effective therapeutic anticoagulants to limit or prevent thrombus formation. It is most desirable to develop agents that inhibit coagulation without directly inhibiting thrombin but by inhibiting other steps in the coagulation cascade lice factor Xa and/or factor Vila activity. It is now believed that inhibitors of factor Xa carry a 5 lower bleeding risk than thrombin inhibitors (A. E, P. Adding. B. M. Reline, Drugs of the future 2000, 25,369-383} Low molecular weight, factor Xa-specific blood clotting inhibitors that are effective but do not cause unwanted side effects have been described, for example, in WO-A-95/29189. However, besides being an effective factor Xa-specific blood clotting inhibitor, it is desirable 10 that such inhibitors also have further advantageous properties, for instance stability in plasma and liver and selectivity versus other serine proteases whose inhibition is not intended, such as thrombin. There is an ongoing need for further low molecular weight factor Xa specific blood clotting inhibitors, which are effective and have the above advantages as well. 15 Specific inhibition of the factor Vila/tissue factor catalytic complex using monoclonal antibodies (WO-A-92/06711) or a protein such as chloromethyl ketone inactivated factor Vila (WO-A-96/12800, WO-A-97/47651) is an extremely effective means of controlling thrombus formation caused by acute arterial injury or the thrombotic complications related to bacterial septicemia. There is also experimental evidence suggesting that inhibition of factor Vila/tissue 20 factor activity inhibits restenosis following balloon angioplasty. Bleeding studies have been conducted in baboons and indicate that inhibition of the factor Vlia/tissue factor complex has "' the widest safety window with respect to therapeutic effectiveness and bleeding risk of any anticoagulant approach tested including thrombin, platelet and factor Xa inhibition. Certain inhibitors of factor Vila have already been described. EP-A-987274, for example discloses 25 compounds containing a tripeptide unit, which inhibit factor Vila. However, the property profile of these compounds is still not ideal, and there is an ongoing need for further low molecular weight factor Vila inhibitory blood clotting inhibitors. WO-A-99/33S0Q discloses indole derivatives, which inhibit factor Xa activity. 30 The present invention satisfies the above needs by providing novel compounds of the formula I which exhibit better factor Xa and/or factor Vila inhibitory activity and are favorable agents with high bioavailability. Thus, the present invention relates to compounds of the formula I, is unsubstituted or mono-, di- or trisubstituted independently of one another by R11 Rit is halogen, -OH, =0, -(Ci-Csj-alkyl, -(Ci-C4}-alkoxy, -HO2, -C(0)-OH, -CN, -NH2, -C(0)-0-(CrC4)-alkyl, -(Ci-CsJ-alkyisuifonyl, -SO1, -C(0)-NH-(Ci-C8)-alkyl, -C{0)-N-[{Ci-C8}-alkyll2, -NR1'-C(0)-NH-(Ci-Ca)-alkyl, ■C(0}-NH,_ -SR10, or -NR'"-C(0)-NH-[(CrCa)-alkyl],. wherein R" is hydrogen atom, -(Ci-Caj-perfluoroalkyl or-(Ci-C6}-alkyi, V is 1. a 3-to 7-membered cyclic residue, containing up to 1,2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-, di- or trisubstituted independently of one another by Ri-*, 2. a 6- to14-membered aryl, wherein aryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R""*, or 3. a monocyclic or bicyclic 4- to 14-membered heteroaryl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R1', G is a direct bond, -(CH,}1-NR'°-S0,-NR'°-(CH,)„-, -(CH,)1-CH(0H)-(CH,)1-, -(CH,)1-, -(CH,)1-0-(CH,),-, -[CH3)1-C(0)-NR1° -[CH,)„-, -(CH,)-S02-[CH,)1-. ■(CH2)„,-NR1"-C(0)-NR1"-(CH,}„-_-(CH,)1-NR1'-C(0)-(CH,)1-, -(CH2),-C(0HCH,)1-,-{CH,)-S-(CH,)„-,-(CH,)„-S0,-NR1°-(CH,),-, -(CH2)n.-NR1"-S0,-(CH,)„-, -(CH,)1-NR1°-. -(CH,)1-0-C(0)-NR1°-(CH,)„- or -(CHj1-NR1°-C(0)-0-(CH,)„-_ n and m are are independently of one another identical or different and are the integers zero, 1, 2,3,4, 5 or 6, Ri1is hydrogen atom, -(Ci-CE)-perfluoroalkyt or-{Ci-C5)-alkyl, M is 1. a hydrogen atom, 2. -(Ci-Caj-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R11 3. -qO1NRiiRi1, 4. -{CH,)„-NR-, 5. -(C6-Ci4)-aryl, wherein aryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R1"*, 6. -(G-Ci4}-heteroaryl, wherein heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R", 7. (Cj-Cyj-cycloalkyl, wherein said cycloalkyi is unsubstituted or mono-, di-or trisubstituted independently of one another by R", or 8. a 3-to 7-membered cyclic residue, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-, di- or trisubstituted independently of one another by K1"*, wherein R11 is defined above, Rii and R12 are Independently of one another identical or different and are 1. hydrogen atom, 2. -(Ci-Cej-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R11, 3. -(G-Ci4)-aryl-(Ci-C4)-alkyl-, wherein alkyl and aryl independently from one another are unsubstituted or mono-, di- or trisubstituted by R'1, 4. -(C6-Ci4)-ary!-, wherein aryl is unsubstituted or mono-, dl- or trisubstituted independently of one another by R""1, 5. -(C4-Ci4)-heteroaryl, wherein heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R'1 or 6.- (Ci-Ci4)-heteroaryl-(Ci-C4)-alky]-, wherein alkyl and heteroaryl independently from one another are unsubstituted or mono-, di- or trisubstituted by R", R" and Ri1 together with the nitrogen atom to which they are bonded can form a saturated 5- to 7-membered monocyclic heterocyclic ring which in addition to the nitrogen atom can contain one or two identical or different ring heteroatoms chosen from oxygen, sulfur and nitrogen; wherein said heterocyclic ring is unsubstituted or mono-, di- or trisubstituted independently of one another by R", R"is halogen, -NO2, -CN, =0, -OH, -(CrCal-allcyl, -{Ci-C8)-alkoxy, -CF3, phenyl, phenyloxy-, -C(0)-0-R-'i, phenyl-(Ci-C4)-all wherein R1", R11R11 are as defined above and R11, R'* or R'l1areas defined below, R15 and R"*1 are independently of one another hydrogen, -(Ci-G)-a!kyl, or together with the carbon atom to which they are bonded they can form a 3- to 6 membered carbocyclic ring which is unsubstituted or substituted one to three times by R", R11 is -(CrC6}-all a) hydrogen atom, b) halogen, c) -(Ci-C4}-a[kYl, wherein alkyl ts unsubstituted or substituted one to three times by R'1 d) -(Ci-Cj)-perfluoroalkyl, e) phenyl, wherein phenyl is unsubstituted or substituted one to three times by R11, f) -0-(CrC4)-a!kyl, wherein alkyi is unsubstituted or substituted one to three times by R", g) -NO2, h} -CN. i) -OH, j) phenyloxy-, wherein phenyloxy is unsubstituted or substituted one to three times by R", jj) benzyloxy-, wherein benzyloxy is unsubstituted or substituted one to three times by R'1, k) -C(0)-O-Rii, I) -qcj-N-R1iRi1 m) -NR"Ri2, n) -NRiO-SOz-Rio, o) -S-Ri", p) -SOn-R1°, wherein n is 1 or 2, q) -S02-NRiiRi1 r} -C{0)-Rio, wherein R""" is as defined above, s) -C(0}-0-C(RisRifi)-0-C(0)-Ri1 wherein Ri5, RIB and R" are as defined above, t) -C(0)-O-C(RisRie)-o-C(0)0-Ri1, wherein R11, Rie and Ri1 are as defined above, u) residue of formula Va, o -(CQ-C4)-alkyl-C(0)0-{C,-C>alkyl—11O Va 10 . R wherein R'" is defined as above, v) a residue of formula Vb or Vc, O A oK //1 Vb 9 J1 vc w) -NR'"'-(CrC4)-a!kyl. wherein alicyi is unsubstituted or substituted one to three times by R11, x) -OCF3, or y) a residue from the following list -N, N CF, H -i r° 1r° 1r° N-S N-S -N P 0 N i H O 1 O HO o 1"o -4 1M-0" u N-0 O X -N NH \ / and N \ H wherein R""*, R", R11 and R""1 are as defined above, in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts. The present invention also relates to the compounds of the formula ), wherein ROis 1. phenyl, wherein phenyl is unsubstituted or mono-, dl- or trisubstituted independently of one another by R1, 2. a bicyclic 5- to 14-membered heteroaryl selected out of the group indolyl, isoindolyl, benzofuranyl, benzothiophenyl, 1,3-benzodioxoiyl, indazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinolinyi, isoquinolinyl, chromanyi, isochromanyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, purinyland pteridinyl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R1, and in addition is substituted by a residue selected out of the group pyridyi, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyi, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazoiyi, isoxazolyl, thiazolyl, , triazolyl, isothiazolyl, thiadiazoiyi, tetrazolyi, pyrimidlnyl, pyridazinyi and pyrazinyl, wherein said residue is unsubstituted or mono-, di- ortrisubstituted independently of one another by R1 3. a monocyclic 5- to 14-membered heteroaryl out of the group pyridyl, 2-pyridyi, S-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazoiyi, isothiazolyl, triazolyl, tetrazolyi, pyridazinyi and pyrazinyl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R1 and in addition Is substituted by a residue selected out of the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyi, 3-thieny|, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazoiyi, isothiazolyl, triazolyl, tetrazolyi, pyridazinyi and pyrazinyl, wherein said residue is unsubstituted or mono-, di- or trisubstituted independently of one another by R1 R8 is 1. halogen, such as F, CI, Br or I, 2. -m-m1. 3. -(Ci-G}-alkyl, wherein alkyl is unsubstituted or mono-, di1 or trisubstituted independently of one another by halogen, -OH or a methoxy residue, or 4. -0-(CrC4}-alkYl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen or a methoxy residue, provided that R« is at least one halogen,-C{0)-NH2or-0-(Ci-C8)-alkyl residue, if R" is a monocyclic or bicyclic 6- to 14-membered aryl, Q is a direct bond, -C(0)-; -SO2- or -(d-Cel-alkylen, -(Co -C2)-alkylen-c(0)-NR'°-, R"! is hydrogen atom or -(Ci-C2)-alkyl, R1is a direct bond or-(Ci-C2}-alkyien, or Ri-N-R1-V can form a 5- to 7- membered cyclic group out of the group pjperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-dia2epine, 1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole, Isoxazoltdine, 2-isoxazoline, morphoiine, thiazole, isothiazole, thiadiazole or thiomorpholine, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted Independently of one another by R1'. RT'is halogen,-(Ci-C4)-alkyl or-NHz, V is 1. a 3- to 7-membered cyclic residue out of the group containing compounds which are derived from aziridine, azirine, azetidine, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine, pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3.5-triazine, tetrazine, tetrazole, azepine, diazirine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, pyridazine, pjperidine, piperazine, pyrrolidinone, ketopiperazine, furan, pyran, dioxole, oxazole, isoxazole, 2-isoxazoline, isoxazolidine, morphoiine, oxirane, oxaziridine, 1,3-dioxolene, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxaziridine, thiophene, thiopyran, thietan, thiazole, isothiazole, isothiazoline, isothiazoiidine, 1,2-oxathioian, thiopyran, 1,2-thiazine, I.S-thiazole, 1,3-thiazine, 1,4-thiazine,thiadiazineor thiomorpholine, wherein said cyclic residue is unsubstituted or mono-, dl- or trisubstituted independently of one another by R1', 2. phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R'"', or 3. a bicydicS-to 14-membered heteroary! out of the group quinolyl, isoquinolyl and quinoxalinyl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R'', G is a direct bond, -(CH1)1-, or -(CH,)1-NR1°-, m is the integers zero, 1, 2, 3 or 4, RIO is hydrogen atom,-{CrC3)-perfluoroaikyI or-[Ci-C4>alkyl, Mis 1. a hydrogen atom, 2. -(C6-Ci4)-heteroarYl, wherein heteroaryl is a residue out of the group which can be derived from piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, pyridonyl, imidazole, pyrldazine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazo(e, 1,2,4-triazofe, tetrazine, tetrazole, 1r2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, oxazote, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, tetrahydropyran, thJadiazole or thiomorpholine, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted Independently of one another by R'-', 3. -(Ci-Cej-alkyI, wherein alkyl is unsubstituted or mono-, di- or trisu bstituted independently of one another by R1", or 4. {C3-C6)-cycloalkyl, R1, R'*, R1 R1and R' are independent of one another are identical or different and are a) hydrogen atom, b) F. CI, Br. c) -(Ci-C4)-alkyl, wherein alkyl Is unsubstituted or substituted by R'1, d) -CF3 e) phenyl, wherein phenyl is unsubstituted or substituted one to three times by R", f) -0-(Ci-C4)-alkyl, wherein alkyl is unsubstituted or substituted by R'1, g) -NOz, h) -CN, i) -OH. j) phenyjoxy-, wherein phenyloxy Is unsubstituted or substituted by R'1, jj) benzyioxy-, wherein benzyloxy is unsubstituted or substituted by R", k) -C(0)-0-R", I) -C(0)-N-RT'Ri2, m) -NR"Ri1, n) -NRiO'S02-Ri«, o) -SOn-R'"', wlierein n is 1 or 2, p) -SOz-NRiiRi1, q) -C(0)-R1° r) -C(0)-0-C(Ri5RiG).o-C(0)-Ri1 wherein R1s, Ri6 and R-"? are as defined above, s) -C{0)-O-C(R'5R->6)-0-C(0)0-Ri', wherein R11. Rie and R""1 are as defined above, t) residue of formula Va -{Co-C1alky1-CCO)CKCi-C4)-a!kyl-110 11 u) a residue of formula Vb or Vc, O °K //1 Vb 9 ,N vo v) -OCF3, or w) a residue from the following list I 11N CM, 1 N CF3 1NN1 "1 M A.,.OMe N 0 H H ""1 H •* O H 1 "N' R" is halogen, -NO2, -CN, =0, -OH, -{Ci-Cal-alkoxy, -CF3, -ClO1O-R-1i, -C(0)-N-R"Ri1-NRiiRi2,-NR'"'-SO2-R1°,-S0n-R'"', wherein n is 1 or 2, -S02-NR-''Ri1-C(0}-Rio.-{CD-C4)-alkyl-C(0)-0-C{Ri5Ri6)~0-C(0)-Ri1 -{Co-a)-alkyl-C[0)-0-C(R15Ri1}-0-C(0)0-R11 or a residue of formula Va, -(Co-C,)-alkyl-C(0)0-(C,-C,)-alkyl —V1° 11 ,wherein R1°, R",R'1Ri1 iV1 or R"are as defined above, in all its stereojsomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts. 5 The present invention also relates to the compounds of the formula I, wherein Ri1is 1. phenyl, wherein phenyl is unsubstituted or mono-or disubstituted independently of one another by R1, 2. a monocyclic 4- to 14-membered heteroaryl out of the group thienyi, thiadiazolyl, isoxazolyl and thiazoiyl, wherein said heteroaryl is substituted by a 10 residue selected out of the group thienyl, 2-thienyl and 3-thienyl, wherein said residue is unsubstituted or mono- or disubstituted independently of one another by R1, RB is F, CI, Br, -OCH3, -C(0)-NH2 or -O-CF3, 15 Q is a direct bond, -C(0)-; -SO2-, methylene or ethylene, Ri is hydrogen atonn, 20 R1is a direct bond or methylen, or Ri-N-R1V can form a 5- to 7-membered cyclic group out of the group pyrrolidine, piperidine and piperazine, R-i1 Is -C(O)-0-R'i, -C[0)-N-RiiRi2 , -NRi1R11 -NRio-SOz-R1", -SOn-R1", wherein n is 1 or 2, 25 -S02-NR11R12, -C(0)-Rio, -(G-C4)-alkYl-C(O)-O-C(Ri5R'6).o.c(0)-Ri', -(G-OValkyi-CtO1O-qRisRi1l-O-qojO-R1'. or a residue of formula Va, -(C,-C,)-alkyl-C(0)0-CH3—tY0 11 wherein R'1 R11.R11Ri1, RI6 or R" are as defined above, 30 Ri" is halogen, methyl, ethyl or -NHz, V is 1. a residue out of the group containing compounds which is derived from isoquinoline, quinolline, quinazoiine, piperidine, azetidine, pyrrolidine, tetrahydropyrane, ptperazJneand isoxazole, wherein said cyclic residue is unsubstituted or mono- or disubstituted independently of one another by R", or 2. phenyl, wherein phenyl is unsubstituted or mono- or disubstituted independently of one another by R", or 10 G is a direct bond, -(CH1)1-, or -(CH1l1-NR'-, m is the integers zero, 1 or 2, Ri" is hydrogen atom or -(Ci-C4)-alkyl, M is a hydrogen atom, [CrC4)-alkyI, imidazolyl, pyrazolyl, pyrrolidinyl, tetrahydropyranyi, 15 piperidinyl, pyridinyi, pyrimidyl, pyrazinyl, pyridazinyl, or (C3-G)-cycloalkyl, wherein said cyclic residues are unsubstituted or mono- or disubstituted independently of one another by R1' R1 R**, R1 R1and R1 are independent of one another are identical or different and are 20 a) hydrogen atom, b) F, CI, c) -(Ci-G)-alkyl, wherein alkyl is unsubstituted or substituted by R11 d) phenyl, wherein phenyl is unsubstituted or substituted one to three times by R'1, e) -0-(CrG)-alkyl, wherein alkyl is unsubstituted or substituted by R11 25 f) -ClOj-O-Ri-", g) -C(0)-N-R"R'1 h) -NR"Ri1 i) -NRT'-S02-Ri°, i) -S0z-NRiiR-'2, 30 k) -ClOj-Rio I) -C(0)-0-C(Ri5Ri6)-0-C(0)-R", wherein R1\ R11 and R11 are as defined above, m) -C(O)-0-C(Ri3Ri6)-O-C(O)0-Ri1 wherein R11 R11 and R11 are as defined above. n) a residue of formula Va ,0 -{Co-C>a)kyf-C(0)0-CHj—4v1O Va o) a residue of formula Vb or Vc, O 0= Vb 9 N vc N-4 )=H 5 p} a residue from the following list o 0 N'1 1CH3 11N CF3 H "■ '1 H in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts. 10 The present invention also relates to the compounds of the formula I, which are 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1 H-lndole-2-carboxylic acid (1- isopropyl-piperidin-4-yl)-amide, 15 1-[5-(5-Ch[oro-thiophen-2-y!)-isoxazol-3-ylmethyl]-5-methanesulfonyl-1H-indole-2-carboxy,lic acid (1-isopropyl-piperidin-4-yl)-amide, l-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yImethyl]-5-nitro-1H-indole-2-carhoxYlicacid (1-isopropyl-piperidin1-yl)-amide, 20 5-Ben2yioxy-'t-[5-(5-ch(oro-thiophen-2-yi)-isoxazol-3-ylmethyl]-1H-indo(e-2-carboxyi!c acid{1-isopropyl-piperidin-4-Yl}-amide, 5-Chloro-1-[5-{5-chloro-thiophen-2-y!)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacld {1-25 isopropyi-piperidin-4-yl)-amide, /7 1-[5-(5-ChIoro-thiophen-2-yl)-isoxazol-3-y!methy!]-5-methoxy-1H-indote-2-carbQxyiic acid [1-fsopropyl-piperidJn-4-yl)-amide, 5 1-[5-(5-Chloro-thiophen-2-yt}-fsoxazol-3-ylmetfiy[]-6-methoxy-1H-indole-2H:arboxylic acid (1-isopropyl-piperidin-4-yl}-amide, 1-[5-(5-Chloro-thiophen-2-yi}-isoxazol-3-ylrnethyl]-5-methy!-lH-indole-2-carboxylicacid (1-isopropyi-piperidin-4-yl)-amide, 10 1-[5-(5-Qiloro-thiophen>2-yl)-isoxazoI-3-ylmethyl]-4,6-dimethoxy-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-annide, 1 -[5-[5-Chloro-th(ophen-2-y))-i50xazol-3-y)methyl]-5,6-dimethoxy-1 H-indole-Z-carboxyHc add 15 (1-isopropyl-piperidin-4-yl)-amide, 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-7-nitro-1H-indo!e-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide, 20 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-trifluoromethoxy-1H-indole-2-carboxylic acid (1-isopropyl-piperidIn-4-y!]-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-lH-indole-2-carboxylicacid [1-isopropyl-piperidin-4-yl)-amide, 25 1-[5-(5-Ch!oro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-(21-dimethyi-propionylamino)-1H- indole-2-carboxylic acid (1-isopropyl-piperid(n-4-yO-am(de, 1-[5-(5-Ch(oro-thiophen-2-y()-isoxa2ol-3-yimetiiy[]-4-methoxy-1H-indole-2-carboxylic acid (1-30 isopropyi-piperidin-4-yl)-amide, l-[5-[5 l-[5-(5-Ch!oro-thiophen-2-yl)-i5oxazol-3-ylmethyl]-6-hydroxy-5-methoxy-1H-indo!e-2-carboxylic acid (1 -isopropyl-piperidin1-yl)-amide, 5 1-[5-(5-Chloro-thtophen-2-yf)-isoxa2o)-3-ylmethyl]-4,6-d(fluoro-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-yl)-amide, 4-Benzyloxy-1-[5-{5-chloro-thiophen-2-y!)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxyiic acid (1-isopropyl-piperidin-4-yl}-amide, 10 7-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1 H-indole-2-carboxyiic acid (1-isopropyl-piperid(n-4-yl}-amide, 6-Chloro-1-[5-(5-ch(oro-thiophen-2-yl)-isoxazo[-3-ylmethyl]-lH-indo!e-2-carboxyiicacid (1-15 isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-th!Ophen-2-yI)-isoxazol-3-Ylmethyi]-5-ethyl-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl}-amide, 20 1-[5-(5-Chloro-thiophen-2-y!)-isoxazol-3-ylmethyl]-5-fluoro-1H-indole-2-carboxylic acid [1-isopropy[-piperidin-4-y()-ami'de, l-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-5-nitro-3-phenYl-lH-indole-2-carboxy!icacid (l-isopropyl-piperidin-4-yl)-amide, 25 5-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-phenyi-TH-indoie-2- carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethYl]-5,7-difluorolH-!ndole-2-cafboxylic acid (1-30 isopropyl-piperidin-4-y!)-amide, 1-[5-(5-Chloro-tbiophen-2-y!)-isoxazol-3-ylmethyl]-5,7-dinitro-1H-indote-2-carboxYlic acid (1-isopropyl-piperidin-4-y!)-amide. 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-vlmethyl]-lH-indole-2-carboxylic acid (3,4,5,6-tetrahydro-2H-[l,4']bipyridinyl-4-yl)-amide, 5 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methy!-1H-indo[e-2-carboxyiicacid (3,4,5,6-tetrahydro-2H-[T,4']bipyridinyM-yl)-amide, 1-[5-(w:hloro-thiophen-2-yl}-isoxazol-3-ylmethyi]-5-nitro-1H-indo!e-2-carboxylicacid (3,4,5,6-tetrahydro-2H-[l,4']bipyridinyl-4-yl)-amide, 10 {1-[5-(5-Chion>thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-['l-{pyridin-4-ylamino)-piperidin-1-y!]-methanone, {V[5-[5-Chloro-thiophen-2-yi)-isoxazol-3-yimethyl]-5-nitro-1H-indo!-2-y!}-[4-(pyridin-4-15 y!amino)-piperidin-l-yl]-methanone, {1-{5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-7-methyl-1H-indol-2-y!}-t4-(pynd(n-4-ylamino)-piperidin-1-yl]-methanone, 20 {l-[5-(5-Chioro-thiophen-2-yl]-isoxazol-3-yimethyl]-lH-indoi-2-yf}-(4-isopropyiamino- piperidin-1-yl)-methanone, {l-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-ylmethylj-7-methyl-lH-indol-2-ylV-(4- isopropylamino-piperidin-1-yl)-methanone, 25 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-YlmethYl]-TH-indole-2-carboxyl!cacid (1-ethyl-P)peridin-4-yl)-amide, 1-[5-(5-ChlorQ-thiophen-2-yl)-isoxazol-3-y!methyl]-7-methyl-lH-indo!e-2-carboxylic acid (1-30 ethy!-piperidin-4-yl)-amide, {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-Ylmethyl]-lH-indDl-2-yl}-(4-pyrrolidin-l-yl- piperidin-1-y()-methanone, [1,4']BipiperidinYl-r-yl-{l-[5-(5-chloro-thiophen-2-yl}-isQxazol-3-yimethyl]-1H-indol-2-y[}-methanone, 5 1-[5-(5-ChIoro-thiophen-2-y()-isoxazol-3-y[methyl]-TH-indo(e-2-carboxylicacid (3- pyridin-4-yI-4,5-dihydro-isoxazol-5-ylmethyl)-amJde, {1-[5-{5-Chloro-thiophen-2-yl)-isoxazo}-3-ylmethyl]-1H-indo!-2-ylH4-pyridin11-y!methyi-piperazin-1-yl)-methanone, 10 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyi]-1H-indole-2-carboxylicacid (1- isopropyl-piperidin-4-ylmethyl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-Indole-2-carboxylicacid (3,4,5,6-15 tetrahydro-2H-[1,4']bipyridifiyM-yImethyI)-amide, 1-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1- cyclopropyl-piperidin-4-yl)-amide, 20 l-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-y)methy!]-lH-indo)e-2-carboxyiicacid [1- (tetrahydro-pYran-4-yl)-piperidin-4-yl]-amide, V[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-Ylmethyl]-1 H-indole-2-carboxylIc acid (1- cyciopentyl-pipendin-4-yl)-am ide, 25. l-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indoie-2-carboxylic acid (1- cyclohexyl-piperidin-4-yl)-amide, l-(3-Methoxy-benzyl)-1H-indole-2-carboxylicacid {1-isopropyl-piperidin-4-y))-amide, 30 1-(3-Methoxy-ben2yI)-1H-indole-2-carboxy!ic acid {l-i5opropyl-piperidin-4-yimethY!)-amide, 1-(3-Methoxy-benzyl)-1H-jndole-2-carboxylic acid (3,4,5,6-tetrahydro-2H- [1,4']bipyridinyl4-yimethyl)-amide, (4-lsopropylamino-piperidin-l-yl}-[1'{3-methoxy-benzyl)-1H-indol-2-yl]- methanone, 5" l-{3-Methoxy-benzyl)-1H-indole-2-carboxylic acid {3,4,5,6-tetrahydro-2H- [1,4']bipyridinvl-4-y))-amide, [1-(3-Methoxy-ben2yl)-1H-!ndol-2-yI]-[4-{pyridin-4-ylaminoj-piperidin-1-y(]-methanone, 10 4-Methoxy-1-(3-methoxy-benzY!)-1H-indole-2-carboxylicacid (l-isopropyl-piperldin1-yl)-amide, 5-Chloro-1-(3-methoxy-benzyl)-1 H-indole-2-carboxylic acid {l-isopropyl-piperidin-4-yl)- amide, 15 6-Methoxy-1-(3-methoxy-ben2yl)-lH-indole-2-carboxYlicacid (1-lsopropyl-piperidin-4-yl)-amide, 1-(3-Methoxy-benzy!)-5-methyl-1H-indole-2-carboxylic add {1-isopropyl-piperidin-4-yl)- amide, 20 5-Ben2yloxy-1-(3-methoxy-benzyll-l H-indo!e-2-carboxylic acid (1-rsopropyl-pipendin-4- yl)-amide, 1-[3-Methoxy-ben2yl)-5-nitro-lH-indole-2-carhoxylic acid (l-isopropyl-pipendin-4-yl)- amide, 25 5-Methoxy-1-(3Tmethoxy-benzyl)-lH-indole-2-carboxylie acid (1-isopropyl-piperidin-4-yl)-amide, l-(3-Methoxy-ben2oyi)-1H-indole-2-carboxyIicacid (l-i50propy!-pjpendin-4-yl)-amide, 30 1-(3-Methoxy-benzenesuIfonyl)-lH-indole-2-carboxvlicacid (1-isopropyl-piperidin-4-yl)-amide, 1-(4-Methoxy-phenyl)-1H-indole-2 1-[4-MethQxy-pheny))-lH-indole-2-carbdxylic acid (3,4,5,6-tetrahydr{>-2H- [1,4']bipyridinyM-yl)-amide, 5 [4-!sopropylamino-piperidin-1-y!)-[1-(4-methoxy-phenyl)-1 H-indol-2-yl]- methanone, 1-(3-Methoxy-phenyi)-1H-indole-2-carboxyiicacid {Visopropyl-piperidtn-4-Yl}-amide, 1-(3-Chloro-phenyl}-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)- amide. 10 1-(3-Chloro-phenyl)-1H-indole-2-carboxylicacid (3,4,5,6-tetrahydro-2H- [1,4']bipyridinyl-4-y!)-amide, 1-[3-Chloro-phenyl)-lH-indole-2-carboxylic acid (1-isopropyl-piperidin-4-ylmethyl)- amide, 15 T-(3,5-Dichloro-phenyi}-1H-indole-2-carboxylic acid {T-isopropyI-piperldin-4-yl}- amide. 1-(4-Ch!oro-phenyl)-1H-indole-2-carboxy!ic acid {1-isopropy!-piperidin-4-yl)- amide, 20 1-(6-Ch!oro-benzo[b]thiophen'2-ylmethyl}-TH-indole-2-carboxylic acid (l-lsopropyi- piperidin1-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yi)-[l,3,4]thiadiazol-2-ylmethyl]-1H-indole-2-carboxylicacid (l-i5opropyl-piperidin-4-yl)-amide, 25 1-[3-[5-Chloro-thiophen-2-yl)-isoxa2ol-5-ylmethYl]-1H-indole-2-carboxylic acid {1- jsopropyl-piperidin-4-yl)-amide, 3-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid (1-30 isopropy!-piperidin-4-yl)-amide, 3-Bromo-l-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-Ylmetiiyl]'lH-indoIe'2-carboxylicacid (1-i5opropyl-piperidin-4-yl)-amide. 1-(4-Ch!oro-benzyi}-1H-indole-2-carboxYlic acid (1-isopropyl-piperidin-4-yl)-amide 1-{4-Chioro-benzyi)-1H-indole-2-carboxylicacid (3,4,5,6-tetrahYdro-2H-[1,4']bipyridinyl-4-y!)-amide, 1-{2,4-Dichloro-benzyl)-1 H-indole-2-carboxylJc acid (l-isopropyl-piperidin-4-yl)- amide, 1-(4-Methoxy-benzyl)-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide, ) (4-lsopropylamino-piperidin-1-yi)-[l-(4-methoXy-ben2yl)-1H-indoI-2-Yl]- methanone, 1-(4-,Trifiuoromethoxy-ben2yl)-1H-indole-2-carboxyiic acid (1-isopropyl-piperidin-4-yl)-amide, 5 l-(2-Ch!oro-benzyl)-1H-indole-2-carboxyiic acid (1-lsoprQpYl-piperidin-4-yl)- amide 1-(2-Chloro-benzyl)-1H-indoie-2-carboxyl(c acid (3,4,5,6-tetrafiydro-2H- [1,4']bipyridinyl-4-yl)-amide, 0 1-(2-Chloro-ben2yl)-1H-indole-2-carboxyllcacld (3,4,5,6-tetrahydro-2H- [1,4']bipvridinyl-4-ylmethyl)-amide, 1-(3,5-Dicbloro-benzyi)-1H-ifidole-2 3-Fluoro-V[5-(5-chioro-thiophen-2-yl)-isoxa2oi-3-y!methyl]-1H-indoIe-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amJde, 30 T-[5-(5-Chloro-thiophen-2-yi)-isoxa2oi-3-ylmethyl]-3-cyano-1H-indole-2-carboxylic acid (1-isopropy!-piperidIn-4-y!)-amide, 1-[5-(5-Chloro-thiophen-2-yi)-(soxazol-3-ylmethyl]-3-cyano-7-methyi-1H-indo(e-2- carboxyiic acid (1-isopropyl-piperidin-4-yl)-amide, T-[2-(5-Ch)oro-thiophen-2-yl)-th(azol-5-Ylmetbyl]-1H-indoIe-2-carboxy)icacid(1-isopropyi-5 piperidin-4-yl)-amide, 1-(3-Chloro-benzyl)-lH-indole-2-carboxyiicacid (l-isopropyl-piperidin1-yl)-amide, [1-p-ChIoro-benzy[)-1H-indoI-2-yl]-(4-i5opropy[amino-piperidin-1-yl)- methanone, 10 1-[2-(4-Chtoro-phenyl)-ethyl]-1H-indole-2-carboxylicacid (1-isopropyi-piperidin-4-yl)-amide, 1-[2-(2,4-Dichlofo-phenyl)-ethyl]-1H-indole-2-carboxy!ic acid [l-tsopropyNplpendin-4- y()-amide, 15 1-[2-(3-Methoxy-phenyl)-ethyl]-1H-indoie-2-carboxylic acid (1-isopropyi-piperldin-4-yl)- amide, 1-[2-[4-Chloro-phenyi)-ethyl]-4-nnethoxy-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl}-amide, 20 4-Bromo-1-[5-(5-chioro-thiophen-2-yI)-isoxazo(-3-y(methyl]-1H-indole-2-carboxv(ic acid (1-isopropyi-piperidin-4-yl}-amide, 1 -[5-{5-Chloro-thJoph en-2-yl)-isoxazoi-3-ylmethyl]-4-m ethyl-1H-J n do I e-2-carboxyiic acid (1 -isopropyi-piperidin1-yl)-amide, 25 5-Bromo-1-[5-{5-chioro-thiophen-2-yi)-isoxaZDl-3-ylmethyi]-lH-indole-2-carboxylicacid (1-isopropyi-piperidin-4-yi)-amide, 1-[5-[5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-cyanQ-1H-indole-2-carboxylicacid (V 30 isopropyl-piperidin-4-yl)-amide, 1-[5-[5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-trifluoromethyl-1H-indole-2-carboxyiic acid (l-isopropyl-piperldin-4-yl}-amide, 1-[5-(5-Chloro-tliiophen-2-yl)-isoxazol-3-ylmethyr]1,7-dimethyl-lH-indole-2-carboxyiIc acid (1-isopropyl-piperidin-4-yl}-amide, 5 1-[5-(5-ailoro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4,7-diniethoxy-1H-indo!e-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-annide, 4,7-Dichloro-1-[5-{S isopropYl-p!peridin-4-y!)-arnide, 4-Chloro-l-[5--{5-chloro-thioplien-2-Yl)-i50xa2oI-3-y!methyl]-1H-indole-2-carboxylic acid [1-15 isopropyl-piperidin-4-yl)-amide, l-[5-{5-Chloro-thiophen-2-yl)-isoxa2oI-3-y[methyl]-lH-indole-2-carboxylic acid (4- metbyl-piperazin-1 -yl)-aniide, 20 [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazoi-3-YlmethYll-7-methYt-1H-indole-2-carbonyl]-(1-isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester, [{1-[5-(5-Chloro-thiophen-2-yi)-isoxazo!-3-yimethyl]-7-methyl-1H-indo!e-2-carbonyl}-[V i5opropy!-piperidin-4-y!)-amino]-aceticacid, 25 l-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethYl]-lH-indole-2-carboxy!icacid [l-(Vethyl-propy!)-piperidin-4-yl]-amide, l-[5-(5-Chloro-thiophen-2-yl)-isoxazoi-3-ylmethYl]-lH-indole-2-carboxylicacid (1- methyl-30 piperidin-4-yi)-amide, l-[5-(5-Chtoro-tiiiophen-2-Yl)-isoxazo(-3-y(methyi]-1H-indo(e-2-carboxyiic acid [1- (2,2,2-trif!uoro-ethyi)-piperidin-4-yi]-amide, 1-[5-(5-Chioro-thiophen-2-yl)-isoxazol-3-ylmethy!]-lH-mdole-2 l-[5-(5-Chloro-thiophen-2-yI)-isoxazol-3-ylmethyl]-1 H-indole-2-arboxylic acid (1-methanesulfonyl-piperidin-4-yl)-amide, 1-[5-{5-Chioro-thiophen-2-yl}-isoxa2ol-3-ylmethyl]-1H-indole-2-carboxylic acid (1- acetyl-piperidin-4-yi)-amide, 1-[5-(5-Chloro-thiophen-2-yi}-isoxa2ol-3-ylmethyl]-1H-indo!e-2-carboxyiicacid [1-(2-chloro-pyrim(din-4-yl)-piperidin-4-yl]-am(de, I 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-y!methyl]-1 H-indole-2-carboxylic acid (1- pyrimidin-4-yl-piperidin-4-yl)-amide, {1-[5-[5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indol-2-yi}-[4-{pyridin-4-y(oxY)-piperidin-') 1-yl]-methanone, l-[5-{5-Ch!oro-thiophen-2-y!)-isoxazoI-3-ylmethy!]-1H-indole-2-carboxylicacid [4-(1H-imidazol-4-yl)-phenyl]-amide, 1-[5-(S-Chloro-thiophen-2-yl)-tsoxazol-3-ylmethy[]-1H-indole"2-carboxyIicacid (4- pyridin-3-yl-5 thiazol-2-yl)-arnide, 1-[5-(5-Cb)oro-thiophen-2-y))-isoxazoi-3-ylmethy)]-1H-indo)e-2-carboxylicacid[3-(pyrroiidine-1-carbonyl)-4,5'dihydro-isoxazol-5-ylmethyl]-amide, iO 1-[5-(5-Chloro-thiophen-2-yl)-isoxazoi-3-ylmethyl]-1H-indole-2-carboxYlic acid (1- isobutyl-piperidin-4-yl)-amide. 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-y!methyl]-1H-indole-2-carboxylicacid (1- propyl-piperidin-4-yl)-amide, 4-({1-[5-(5-Chlor(>-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indoie-2-carbonyl}-amino)-5 pJperidine-l-arboxy)icacid methy) ester, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid (4- isopropyl-piperazin-1-yl)-aniide, 10 V[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid [4-ethyl-piperazin-1-yl)-amide, 1-[5-(5-Ch!oro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid pyridJn- 4-yi-(3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide, 15 1-[5-(5-ChIoro-thiophen-2-yi)-isoxazol-3-yitnethyl]-5-nitro-lH-indole-2-carboxy!icacid pyridin-4-yl-{3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amIde, 1-[5-[5-Chloro-thiophen-2-yl}-isoxa2ol-3-yimethyI]-3-cyano-1H-indofe-2-carboxyIicacid (3,4,5,6-20 tetrahydro-2H-[l,4']bipyridinyl-4-yl)-amide, 1-[5-{5-Chloro-thiophen-2-yi)-isoxa2ol-3-ylmethyl]-3,7-diiodo-4-methoxy-lH-indole-2- carboxylic acid (Visopropyi-piperidin-4-yl)-arnide, 25 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylniethyl]-3,7-dicyano-4-methoxy-lH-indole-2-carboxylic acid (l-isopropyl-piperidin-4-yl)-amide, l-[2-(4-Chioro-pbeny))-thiazpl-4-ylmethyl]-lH-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 30 l-(l,7-Dichloro-isoquinolin-3-yimethyl}-lH-indole-2-carboxylicacid (l-isopropyl- piperidin-4-yl)-amide, 1-[3-(4-Chloro-phenyl)-isoxazol-5-ylmethyl]-1H-indole-2-carboxyiicacid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-{4-Chloro-pheny!)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1-isopropyl- piperidin-5 4-yl)-amtde, 1-[3-{4-Chloro-phenyl}-[T,2,4]oxadtazol-5-ylmethyl]-l H-indole-2-carboxyiic acid (i- isopropyl-piperidin-4-yl)-amide, 10 1-[(5-Chloro-pyridin-2-ylcarbamoyl}-methyl]-5-methanesuIfonyI-1H-indo!e-2-carboxyiic add (1-isopropyi-piperidin-4-yl)-amide, 1-[(4-Chloro-phenyicarbamoyl}-methyl]-5-methanesulfonyl-1H-indole-2-carboxyilcacid (1-isopropyl-piperidin-4-yl)-amide, 15 5-Chloro-1-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indole-2-carboxylicadd {l-isopropyl-piperidin-4-yl)-amide, 1-[[5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-fluoro-1H-indole-2-carboxyIicacid (1-isopropyi-20 piperidin-4-Y!)-amide, l-[(5-Chloro-pyndin-2-y!carbamoyl)-methyl]-5,7-difiuoro-lHHndole-2-carboxyl!cadd {1-isopropyi-piperidin-4-yl)-amide, 25 S-1-[5-(5-Chioro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1 H-indole-2-carboxylic add [l-etliyl-pyrrolidin-3-yi)-amide, R-l-[5-{5-Chloro-thiophen-2-y!)-isoxazol-3-ylmethy!]-1H-indo]e-2-carboxylicadd {1-ethy!-pyrrolidin-3-yl)-amide, 30 R-1-[5-(5-Chloro-thiophen-2-yl)-isoxazo!-3-yimethyl]-1H-indoie-2-carboxyiicadd [1-isopropyl-pyrrol!din-3-yl)-amide, S-1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indole-2-carboxy!icacid (1- isopropyl-pyrrolidin-3-yi)-amide, [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-trif]uoromethyl-1H-indole-2-carbony!}-(l-5 isopropy|-piperidin-4-yI)-amino]-acetic acid ethyl ester, [{1-[5-(5-Ch!oro-thiophen-2-yl}-isoxazol-3-ylmethYl]-4,7-dimethyl-lH-indole-2-carbonyl}-(l-tsopropy!-piperidin-4-y!)-amino]-acetic acid ethyl ester, 10 [{l-[5-[5-Chloro-thiophen-2-yl}-isoxazol-3-yimethyl]-4,7-dimethoxY-1H-indole-2-carbonyl}-(1-isopropyi-piperidin-4ryi}-amino]-aceticacid ethyl ester, K4,7-Dichloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonYl]-(l-isopropyl-piperidin-4-yl}-amino]-acetic acid ethyl ester, 15 [{5,7-Dichloro-1-[5-(5-chloro-thiopheTi-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}-(l-isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester, [{4-Chloro-l-[5-{5-chloro-thiophen-2-yl)-isoxazol-3-yimethYl]-TH-indole-2-carbonyl}-(1-20 isopropy|-piperidin-4-y!)-amino]-acetic acid ethyl ester, [{1-[5-(5-ChlorQ-thiophen-2-yl)-isoxazol-3-ylmethyl]1-trifluoromethyl-1H-indole-2- carbonYl}-(1-isopropyl-piperidin-4-yl)-amino]-acetic acid, 25 [{l-[5'(5-Ch!oro-thiophen-2-ylHsoxazol-3-YlmethylH,7-dimethyl-1H-indole-2-carbony!}-(1-isopropyl-piperidin-4-yl)-amino]-acetic acid, [{l-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4,?-dimethoxy-1H-indole-2- carbonyI}-(l-isopropyl-piperidin-4-y!)-amino]-aceticacid, 30 [{4,7-Dichloro-1-[5-(5-chioro-thiophen-2-yl)-isoxazol-31ylmethyl]-1H-indo!e-2-carbonyl}-(1-isopropYl-piperidin-4-yl)-amino]-acetic acid, [{5,7-Dichloro-1-[5-(5-chloro-thiophen-2-yI)-isoxazol-3-yimethyl]-1H-indole-2-carbonyl)-{1-isopropyl-piperidm-4-yi)-annino]-aceticacid, [{4-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-l H-indole-2-carbonyl}-(l-5 isopropyl-piperidin-4-yI)-amino]-aceticacid, 1-[5-{S-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-yIcarbamoyl)-lH-indole-5-carboxylic acid tsopropyl ester, 10 l-[5-(5-Chloro-thiophen-2-yl]-isoxa2ol-3-ylmethyl]-2-(1-i5opropyl-piperidin-4- ylcarbamoyO-1H-indo!e-5-carboxylic add, 1-[5-(5-Chloro-thiophen-2-y!)-isoxazol-3-yimethyl]-5-hydroxymethyi-1 H-indole-2- carboxylic acic (1-]50propy!-pJperidin-4-yi)-amide, 15 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethy!]-2-(1-isopropyl-piperidin4-yIcarbamoyl)-1H-indole-5-carboxylic acid ethyl ester, 1-[5-(5-Chioro-thiophen-2-yi)-isoxazol-3-ylmetliyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-20 indole-5-carboxylicacid methyl ester, l-[5-(5-Chloro-thiGphen-2-y!)-isoxazol-3-ylmethYl]-2-(1-i5opropyl-piperidin-4-ykarbamoyl)-lH-indole-5-carboxytic acid 2,2-dimethyi-propionyloxymethyl ester, 25 1-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-2-[1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-5-carboxylicacid isopropyl ester, l-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-2-(T-isopropyl-piperidin-4-ylcarbamoyl}-1H-indoie-5-carboxylicacid, 30 1-[(4-Chloro-phenylcarbamoyl)-methyi]-2-{1-isopropYi-piperidin-4-ylcarbamoyl)-lH-indole-5-carboxylic acid isopropyl ester, 1-[(4-Chloro-phenyicarbamoyl)-methyi]-2-(1-isopropy!-piperidin-4-ylcarbamoyl)-1H-Indoie- 5-carboxylicacid, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yirnethyl]-2-(1-isopropyi-piperJdin-4-y!carbamoyl)-lH-5 indoie-4-carboxylic acid methyl ester, 1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-■mdole-4-carboxylic acid, 10 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmetliyl]-1 H-indo!e-2,5-d!carboxylic acid 5- amide 2-[(1-isopropyi-piperidin-4-yi)-amide], 1-[(4-chloro-phenylcarbamoyl)-niethyl]-lH-indole-2-carboxylic acid (1-isopropyl- piperidin-4-yl)-amide, 15 l-[(5-chloro-thiophen-2-ylcarbamoYl)-methyl]-lH-indole-2-carboxyllcacid (l-isopropyl-piperidin-4-yl)-amide, l-[(4-chloro-2-fluoro-phenylcarbamoyl)-methy!]-1 H-indole-2-carboxy!ic acid (1-isopropyl-20 piperidin-4-y[}-amide, l-[(5-chloro-pyridin-2-ylcarbarnoyl)-methyl]-1H-indole-2-carboxylicacid (l-isopropyl- piperidin-4-yl]-amide, 25 l-[(4-chioro-phenylcarbamoyI)-methyl]-1H-indole-2-carboxYlicacid (3,4,5,6-tetrahydro-2H-I1,4']bipyndinyl-4-ylmethyi)-amide, l-[(4-chloro-phenylcarbamoyl)-methyl]-l H-indoIe-2-carboxylic acid (3,4,5,6-tetrahydro- 2H-[1,4']bipyridinyl-4-yl)-amide, 30 N-{4-ch!oro-phenyl)-2-{2-[4-(pyr!din-4-y[amino)-piperidine-1-carbonyl]-indol-1-y!}~acetamide, w 1-[(4-chIoro-phenylcarbamoyl)-methyl]-1H-indoIe-2-carboxyiic acid (1-cyclopropyl- piperldin-4-yi)-amide, N-(4-chloro-pheny!)-2-[2-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-indol-1-yl]- acetamide, 5 l-[(4-chloro-phenylcarbamoyl)-methyl]-5-nitro-1H-indole-2-carboxy!icacid {1-isopropyl-piperidin-4-y!)-amide, 5-amino-4-chlDro-1-[5-(5-chloro-thiophen-2-y!}-isoxazol-3-ylmethyi]-lH-indole-2-1 carboxyiic 10 acid {1-isopropyl-piperidin4-yl)-amide, 1-[5-(5-chloro-thiophen-2-yl)-isDxazol-3-yimethyi]-lH-Indo!e-2-carboxy!icacid (1-cyanomethyl-piperidin-4-y!)-amide, 15 1-[5-(5-ch!oro-thiophen-2-yl)-isoxazol-3-ylmethy!]-1H-indole-2-carboxylic acid [11(2- hydroxy-ethYl)-piperidin-4-yl]-amide, 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-y[methyl]-TH-indole-2-carboxy!ic acid [1-(2- methoxy-ethy!)-piperidin-l-yl]-amide, 20 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-y!methyl]-lH-indole-2-carboxylicacid (1- '■-- carbamoylmethyl-piperidin-4-yl)-amide, 1-[5-(5-chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1H-indoie-2-carboxylicacid (1-25 methylcarbamoylmethyI-plperidin-4-yl)-amide, 1-[5-(5-chioro-thiophen-2-yl)-isoxa2o!-3-ylmethyl]-1H-indole-2-carboxylic acid [1-(1H- imidazol-2-ylmethyl)-piperidin-4-yl]-amide, 30 1-[5-(5-chloro-thiophen-2-yi)-isoxazol-3-ylmethyl]-lH-indole-2-carboxYlic acid [1-(2-dimethy!amino-acety!)-piperidin-4-yl]-amide, l-[5-(5-Chloro-thiophen-2-Y!)-isoxa2ol-3-Ylmethyl]-2'(1-isopropyl-piperidin1-y!carbamoYl)-1H-indole-5-carboxyiic acid l-ethoxycarbonyioxy-ethyi ester, 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-y!methyl]-2-(1-i50propyl-piperidin-4-Ylcarbamoyl)-1H-5 indole4-carboxyiic acid 1-ethoxycarbonyloxy-ethyl ester, 1-[5-(5-Ch!oro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin1-yicarbamoyi)-lH-indole-4 1-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-Ylnnethyl]-2-{1-isopropyl-piperidin1-ylcarbamoyl)-1H-indole-4-carboxyIic acid 1-(2,2-dimethyl-propionvloxy)-ethyl ester, 15 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropYi-piperidin-4-YlcarbamoY!)-lH-indoIe-5-carboxylicacid 5-methYl-2-oxo-[1,3]dioxol1-ylmethyl, l-[5-(5-Chloro-thiophen-2-yl}-i5Dxazol-3-yimethyl]-2-(l-isopropYl-piperidin-4-YlcarbamoYl)-lH-20 indole1-carboxylicacid 5-methyl-2-oxo-[l,3]dioxol-4-ylmethyl, T-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-ylmethyl]-2-{lHSopropyl-piperidin-4-ylcarbamoyl)-lH-indo!e-5-carboxylicacid l-cyclohexyloxycarbonyloxy-ethyl ester or 25 l1[5-(5-Chloro-thlophen-2-Yl)-isoxazo!-3-Ylmethyl]-2-(l-isopropy|-piperidin-4-ylcarbamoyl)-1H-indole-4-carboxyHc acid l-cyclohexyloxycarbonyloxy-ethyl ester, In general, the meaning of any group, residue, heteroatom, number etc., which can occur 30 more than once in the compounds of the formula 1, is independent of the meaning of this group, residue, heteroatom, number etc. in any other occurrence. All groups, residues, heteroatoms, numbers etc, which can occur more than once in the compounds of the formula I can be identical or different. As used herein, the term alkyl is to be understood in the broadest sense to mean hydrocarbon residues which can be linear, i. e. straight-chain, or branched and which can be acyclic or cyclic residues or comprise any combination of acyclic and cyclic subunits. Further, the term 5 alkyl as used herein expressly includes saturated groups as well as unsaturated groups which latter groups contain one or more, for example one, two or three, double bonds and/or triple bonds, provided that the double bonds are not located within a cyclic alkyl group in such a manner that an aromatic system results. All these statements also apply if an alkyl group occurs as a substituent on another residue, for example in an alkyloxy residue, an 10 alkyloxycarbonyl residue or an arylalkyl residue. Examples of alkyl residues containing 1, 2, 3, 4, 5, 6,7 or Scarbon atoms are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl or octyl, the n-isomers of ail these residues, isopropyl, isobutyl, 1-methylbutyl, isopentyl, neopentyl, 2,2-dimethyibutyi, 2-m ethyl pentyl, 3-methylpentyl, isohexyl, sec-butyl, tBu, tert-pentyl, sec-butyl, tert-butyl or tert-pentyl. 15 Unsaturated alkyl residues are, for example, alkenyl residues such as vinyl, 1-propenyl, 2-propenyl (= allyl), 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 5-hexenyl or 1,3-pentadienyl, or alkynyl residues such as ethynyl, l-propynyl, 2-propynyl (= propargyl) or 2-butynyl. Alkyl residues can also be unsaturated when they are substituted. 20 Examples of cyclic alkyl residues are cycloalkyi residues containing 3, 4, 5 or 6 ring carbon atoms like cyclopropyl, cyclobutyl, cyclopenty! or cyclohexyl, which can also be substituted and/or unsaturated. Unsaturated cyclic alkyl groups and unsaturated cycloalkyi groups like, for example, cyclopentenyl or cyclohexenyl can be bonded via any carbon atom. 25 Of course, a cyclic alkyl group has to contain at least three carbon atoms, and an unsaturated alkyl group has to contain at least two carbon atoms. Thus, a group like (Ci-C8)-aiky! isto be understood as comprising, among others, saturated acyclic (d-Csl-alkyl, (Cj-CG)-cycloalkyl, and unsaturated (C2-G)-alkyl like (C2-C8)-alkenYl or (CrG)-alkynyl. Similarly, a 30 group like (Ci-C4)-alkyl is to be understood as comprising, among others, saturated acyclic (d-C4)-alkyl, and unsaturated (C2-C4)-alkyl like {Cz-C4)-alkenYl or (Cz-Gj-alkynyl. Unless stated otherwise, the term alky! preferably comprises acyclic saturated hydro-carbon residues which have from one to six carbon atoms and which can be linear or branched. A particular group of saturated acyclic alkyl residues is formed by {Ci-C4)-alkyl residues like methyl, ethyl, n-propyl, isopropyl, n-butyl, isobuty!, sec-butyl and tBu. 5 Unless stated otherwise, and irrespective of any specific substrtuents bonded to alkyl groups which are indicated in the definition of the compounds of the formula 1, alkyl groups can in general be unsubstituted or substituted by one or more, for example one, two or three, identical or different substituents. Any kind of substituents present in substituted alkyl 10 residues can be present in any desired position provided that the substitution does not lead to an unstable molecule. Examples of substituted alkyl residues are alkyl residues in which one or more, for example 1, 2 or 3, hydrogen atoms are replaced with halogen atoms, in particular fluorine atoms. 15 The term "mono- or bicyclic 4-to 14-membered heteroaryl" refers to (C4-Ci4}-aryl in which one or more of the 5 to 14 ring carbon atoms are replaced by heteroatoms such as nitrogen, oxygen or sulfur. Examples are azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazoiyl, benzisoxazolyl, benzisothiazolyl, benzimidazalinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, 20 chromenyl, cinnolinyl, decahydrochinolinyl, 2H,6H-1,5,2"dithiazinyl, dihydrofuro[2,3-b]-tetrahydrofuran, fuanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazo[y(, indoiinyi, indolizinyl, indolyl, 3H-indoIyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isoxazoly!, morphollnyl, naphthyridinyl.octahydraisoqulnolinyl, oxadiazolyl, 1,2,3-oxad(a2olyl, T,2,4-oxad(azo(yi, 1,2,5- 25 oxadiazolyl, 13,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyi, phthalazinyl, piperazlnyl, piperidinyl, pteridiny!, purynyi, pyrany), pyrazinyl, pyroazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pryidooxazole, pyridoimidazole, pyridothiazoie, pyridinyl, pyridyl, pyrimidinyl, pyrrolidjnyl, pyrrotinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyt, quinolinyl, 4H- 30 quinolizinyl, quinoxalinyl, quinuciidlnyl, tetrahydrofuranyl, tetrahydroisochinolinyl, tetrahydrochinolinyi, 6H-1,2,5-thiadazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadia2olyl und xanthenyl. Preferred are pyridyl; such as 2-pyridyi, 3-pyridyl or 4-pyridyl; pyrroiyi; such as 2-pyrro!yi and 3-pyrrolyl; furyl; such as2-furyl and 3-furyl; thienyl; such as2-thienyl and 3-thienyl; imidazolyl, pyrazoiyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, tetrazolyl, pyridazinyi, pyrazlnyl, pyrimldinyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyi, 1,3-benzodioxolyl, indazolyl, 5 benzimidazolyl, benzoxazolyl, benzothlazolyl, quinolinyl, isoquinolinyl, chromanyl, isochromanyl, cinnolinyl, quinazoiinyl, quinoxalinyl, phthalazinyt, pyridoimidazolyl, pyridopyridinyi, pyridopyrimidinyl, purinyl and pteridinyl. The term "R' and R1 together with the nitrogen atom and V to which they are bonded form a 5- 0 to 7-membered cyclic group" refers to structures of heterocycles which can be derived from compounds such as piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 13,5-triazine, 1,2,3-triazole, 1,2,4-triazoie, tetrazine, tetrazole, 1,2-diazepine, 13-diazepine, 1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine. 5 The term "a 3- to 7-membered cyclic residue, containing up to 1, 2, 3 or 4 heteroatoms" refers to structures of heterocycles which can be derived from compounds such as , aziridine, azirine, azetidine, pyrrole, pyrrolidine, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine, pyrimidine, pyrazlne, 1,2,3-triazine, 1,2,4-triazine. 1,3,5-triazine, tetrazine, tetrazole, 0 azepine, diazirine, 1,2-diazepine. 1,3-diazepine, 1,4-diazepine, pyridazine, piperidine, piperazine, pyrrolidinone, ketopiperazine, . -.. . furan, pyran, dioxole, oxazole, isoxazole, 2-isoxazoline, isoxazolidine. morpholine, oxirane, oxaziridine, 1,3-dioxolene, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxaziridine, thiophene, thiopyran, thietan, thiazoie, isothiazole, isothiazoline, isothiazolidine, 1,2- 5 oxathiolan, thiopyran, 1,2-thiazine, 1,3-thiazole, 1,3-thiazine, 1,4-thiazine, thiadiazine or thiomorpholine. The term "R" and R11 together with the nitrogen atom to which they are bonded form a saturated or unsaturated 5- to 7-membered monocyclic heterocyclic ring" refers to residues ;0 which can be derived from compounds such as piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine. ketopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine. The fact that many of the before-listed names of heterocycles are the chemical names of 5 unsaturated or aromatic ring systems does not imply that the , the 4-15 membered mono-or polycyclic group could only be derived from the respective unsaturated ring system. The names here only serve to describe the ring system with respect to ring size and the number of the heteroatoms and their relative positions. As explained above, the 4-15 membered mono-or polycyclic group can be saturated or partially unsaturated or aromatic, and can thus be 10 derived not only from the before-listed heterocycles themselves but also from all their partially or completely hydrogenated analogues and also from their more highly unsaturated analogues if applicable. As examples of completely or partially hydrogenated analogues of the before-listed heterocycles from which this group may be derived the following may be mentioned: pyrroline, pyrrolidine, tetrahydrofuran, tetrahydrothJophene, dihydropyridine, 15 tetrahydropyridine, piperidine, 13-dioxolane, 2-imidazoline, imidazoiidine, 4,5-dihydro-l,3-oxazol, 1,3-oxazolidine, 4,5-dlhydro-l,3-thiazole, 1,3-thiazolidine, perhydro-1,4-dioxane, piperazine, perhydro-1,4-oxazine (= morpholine), perhydro-1,4-thiazine (= thiomorpholine), perhydroazepine, indoline, Isoindoline, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, etc. 20 The 4-15 membered mono- or polycyclic group may be bonded via any ring carbon atom, and in the case of nitrogen heterocycles via any suitable ring nitrogen atom. Thus, for example, a pyrrolyl residue can be l-pyrrolyl, 2-pyrrolyl or 3-pyrrolyI, a pyrrolidinyl residue can be pyrrolidin-1-yl (= pyrrolidino), pyrrolidin-2-yl or pyrrolidin-3-yl, a pyridinyl residue can be 25 pyridin-2-yl, pyridin-3-yl or pyridin-4-yl, a piperidinyl residue can be piperidin-1-yl {= piperidino), piperidin-2-yl, piperidin-3-yl or piperidin-4-yl. Furyl can be2-furyl or3-furYl, thienyl can be 2-thienyl or S-thienyl, imidazolyl can be imidazol-1-yl, imidazol-2-yl, ImidazoM-yi or imidazol-5-yl, 1,3-oxazolyl can be 13-oxazol-2-Yl, 1,3-oxazoH-yl or l,3-oxazol-5-yi, 1,3-thiazolyl can be l,3-thiazol-2-yl, 1,3-thiazol-4-yl orl,3-thiazol-5-yl, pyrimidinyl can be 30 pyrimidln-2-yl, pyrimidin-4-y! {= 6-pyrimidinyl) or 5-pyrimidtnyl, piperazinyi can be piperazin-1-yl {- piperazin-4-yl = piperazine) or piperazin-2-yl. Indolyl can be indol-1-yl, indol-2-yl, indol-3-yl, indol-4-y!, indol-5-yl, indol-6-yl or indol-7-yl. Similarly benzimidazolyl, benzoxazolyl and benzothiazol residues can be bonded via the 2-position and via any of the positions 4, 5, 6, and 7. Quinolinyl can be quinolin-2-yI, quinoiin-B-yl, quinolin-4-yi, quinolln-S-yi, quinolin-6-y!, quinolin-7-yl or quinolin-8-yl, isoqinollnyl can be isoquinol-1-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl or isoquinolin-8-yl. in addition to being bonded via any of the positions indicated for quinolinyl and Isoquinolinyi, 1,2,3,4-5 tetrahydroquinolinyl and 11,3,4-tetrahydroisoqulnolinyl can also be bonded via the nitrogen atoms in 1-position and 2-posrtion, respectively. Unless stated otherwise, and irrespective of any specific substltuents bonded to the 4-15 membered mono- or polycyclic group or any other heterocyclic groups which are indicated In the definition of the compounds of the formula I, the 4-15 membered mono-or polycyclic 10 group can be unsubstituted or substituted on ring carbon atoms with one or more, for example one, two, three, four or five, identical or different substltuents like (d-Caj-alkyl, in particular (Ci-Ct)-alkyl, (Ci-C8)-alkyloxy, in particular (CrC4)-alkyloxy, (Ci-C4)-alkylthio, halogen, nitro, amino, ((CrC4)-alkyl)carbonylamino like acetyiamino, trifluoromethyl, trifiuoromethoxy, hydroxy, oxo, hydroxy-(Ci-C4)-alkyl such as, for example, hydroxymethyl or 1-hydroxyethyl or 2- 15 hydroxyethyl, methylenedioxy, ethyl en edloxy, formyl, acetyl, cyano, aminosulfonyl, methylsulfonyl, hydroxycarbonyl, aminocarbonyl, (Ci-C4)-aikyloxycarbonyl, optionally substituted phenyl, optionally substituted phenoxy, benzyl optionally substituted in the phenyl group, benzyloxy optionally substituted in the phenyl group, etc. The substltuents can be present in any desired position provided that a stable molecule results. Of course an oxo group 20 cannot be present in an aromatic ring. Each suitable ring nitrogen atom in the 4-15 membered mono- or polycyclic group can independently of each other be unsubstituted, i. e. carry a hydrogen atom, or can be substituted, i. e. carry a substituent like (Ci-Caj-alky!, for example (CrC4)-alkyl such as methyl or ethyl, optionally substituted phenyl, phenyl-(Ci-C4}-alkyl, for example benzyl, optionally substituted in the phenyl group, hydroxv-(C2-C4)-alkYl such 25 as, for example 2-hydroxyethyl, acetyl or another acyl group, methylsulfonyl or another sulfony! group, aminocarbonyl, (Ci-C4)-alkyloxycarbonyl, etc. in general, in the compounds of the formula I nitrogen heterocycles can also be present as N-oxides or as quaternary salts. Ring sulfur atoms can be oxidized to the sulfoxide or to the sulfone. Thus, for example a tetrahydrothienyi residue may be present as S,S-dioxotetrahydro-thienyl residue or a 30 thiomorpholinyl residue like thiomorphoiin-4-yl may be present as 1-oxo-thiomorpholin-4-yl or l,1-dioxo-thiomorpholin-4-yl. A substituted 4-15 membered mono-or polycyclic group that can be present in a specific position of the compounds of formula i can independently of other groups be substituted by substituents selected from any desired subgroup of the substituents listed before and/or in the definition of that group. The 3-7 membered monocyclic group may be bonded via any ring carbon atom, and in the 5 case of nitrogen heterocycles via any suitable ring nitrogen atom. Thus, for example, a pyrrolyi residue can be 1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, a pyrrolidinyl residue can be pyrrolidin-T-yl (= pyrrolidine), pyrrol idin-2-y I or pyrrol id in-3-yl, a pyridinyl residue can be pyridin-2-yl, pyridin-3-yl or pyridtn-4-yl, a piperidinyl residue can be plperidin-l-yl (= piperidino), piperidin-2-yl, piperidin-3-yl or piperidin-4-yl. Furyl can be 2-furyl or 3-furyl, thienyl can be 2- 10 thienyl or 3-thienyl, imidazoiyi can be Imidazol-l-yl, imidazol-2-yl, imidazol-4-yl or imidazol-5-yl, 1,3-oxazoiyl can be 1,3-oxazol-2-yl, 13-oxazol-4-yl or 1,3-oxazol-5-yl, 1,3-thiazolyl can be 1,3-thiazol-2-Yl, 1,3-thiazol1-yl orl,3-thiazol-5-yl, pyrimidinyl can be pyrimidin-2-yl, pyrimidin-4-yl (= 6-pyrimidinyl) or 5-pyrimidinyl, piperazinyl can be piperazln-1-yl (= piperazin-4-yl = piperazino) or piperazin-2-yi. Unless stated otherwise, and irrespective of any 15 specific substituents bonded to the 3-7 membered monocyclic group or any other heterocyclic groups which are indicated in the definition of the compounds of the formula 1, can be unsubstituted or substituted on ring carbon atoms with one or more, for example one, two, three, four or five, identical or different substituents like (CrCs)-alkyl, in particular (CrC4)-aikyI, (CrG)-alkyloxY, in particular (CrOj-alkyloxy, (Ci-Qj-alkylthio, halogen, nltro, amino, ({C1-C4)- 20 alkyl)carbonyiamino like acetylamino, trifluoromethyl, trlfluoromethoxy, hydroxy, 0x0, hYdroxy-{Ci-C4)-a!kyl such as, for example, hydroxymethy! or 1-hydroxyethyl or2-hydroxYethYl, methylenedioxy, ethylenedioxy, formyl, acetyl, cyano, aminosulfonyl, methylsulfonyl, hydroxycarbonyl, aminocarbonyl, (Ci-Ol-alkyloxycarbonyl, optionally substituted phenyl, optionally substituted phenoxy, benzyl optionally substituted in the phenyl group, benzyloxy 25 optionally substituted in the phenyl group, etc. The substituents can be present in any desired position provided that a stable molecule results. Of course an 0x0 group cannot be present in an aromatic ring. Each suitable ring nitrogen atom in the 3-7 membered monocyclic group can independently of each other be unsubstituted, i. e. carry a hydrogen atom, or can be substituted, i. e. carry a substituent like (d-Csl-alkyl, for example (Ci-C4)-alkyl such as methyl or 30 ethyl, optionally substituted phenyl, phenyl-{CrCi)-alkyl, for example benzyl, optionally substituted in the phenyl group, hydroxy-(C2-C4)-aIkyl such as, for example 2-hydroxyethyl, acetyl or another acyl group, methylsulfonyl or another sulfonyl group, aminocarbonyl, (Ci-Q)-alkyloxycarbonyl, etc. In general, in the compounds of the formula I nitrogen heterocycles can also be present as N-oxides or as quaternary salts. Ring sulfur atoms can be oxidized to the sulfoxide or to the sulfone. Thus, for example a tetrahydrothienyl residue may be present as S,S-dioxotetrahydrothienyl residue or a thiomorpholinyl residue like thiomorphoIin-4-yl may be present as 1-oxo-thiomorpholin-4-yl or 1,1-dioxo-thiomorpholin-4-yl. A substituted 3-7 5 membered monocyclic group that can be present in a specific position of the compounds of formula I can independently of other groups be substituted by substituents selected from any desired subgroup of the substituents listed before and/or in the definition of that group. Halogen is fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine, 10 particularly preferably chlorine or bromine. Optically active carbon atoms present in the compounds of the formula I can independently of each other have R configuration or S configuration. The compounds of the formula I can be present in the form of pure enantiomers or pure diastereomers or in the form of mixtures of 15 enantiomers and/or diastereomers, for example in the form of racemates. The present invention relates to pure enantiomers and mixtures of enantiomers as well as to pure diastereomers and mixtures of diastereomers. The invention comprises mixtures of two or of more than two stereoisomers of the formula I, and it comprises all ratios of the stereoisomers in the mixtures. In case the compounds of the formula I can be present as E isomers or Z 20 isomers {or cis isomers or trans isomers) the invention relates both to pure £ isomers and pure Z isomers and to E/Z mixtures in all ratios. The invention also comprises all tautomeric forms of the compounds of the formula 1. Diastereomers, including E/Z isomers, can be separated into the individual isomers, for 25 example, by chromatography. Racemates can be separated into the two enantiomers by customary methods, for example by chromatography on chiral phases or by resolution, for example by crystallization of diastereomeric salts obtained with optically active acids or bases. Stereochemically uniform compounds of the formula I can also be obtained by employing stereochemically uniform starting materials or by using stereoselective reactions. 30 Physiologically tolerable salts of the compounds of formula I are nontoxic salts that are physiologically acceptable, in particular pharmaceutically utilizable salts. Such salts of compounds of the formula I containing acidic groups, for example a carboxyl group COOH, are for example alkali metal salts or alkaline earth metal salts such as sodium sails, potassium salts, magnesium salts and calcium salts, and also salts with physiologically tolerable quaternary ammonium ions such as tetramethylammonium or tetraethylammonium, and acid addition salts with ammonia and physiologically tolerable organic amines, such as 5 methylamine, dimethylamine, trimethylamine, ethylamine, triethylamine, ethanolamine or tris-(2-hydroxyethyl)amine. Basic groups contained in the compounds of the formula I, for example amino groups or guanidino groups, form acid addition salts, for example with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid or phosphoric acid, or with organic carboxyiic adds and sulfonic acids such as formic acid, acetic 10 acid, oxalic acid, citric acid, lactic acid, malic acid, succinic acid, malonic acid, benzoic acid, maleic acid, fumaric acid, tartaric acid, methanesulfonic acid or p-toluenesulfonic acid. Compounds of the formula 1 which simultaneously contain a basic group and an acidic group, for example a guanidino group and a carboxyl group, can also be present as zwitterions (betaines) which are likewise included in the present invention. 15 Salts of compounds of the formula 1 can be obtained by customary methods known to those skilled in the art, for example by combining a compound of the formula I with an inorganic or organic acid or base in a solvent or dispersant, or from other salts by cation exchange or anion exchange. The present invention also includes all salts of the compounds of the formula ! 20 which, becauseof low physiologically tolerabilrty, are not directly suitable for use in pharmaceuticals but are suitable, for example, as intermediates for carrying out further chemical modifications of the compounds of the formula 1 or as starting materials for the preparation of physiologically tolerable salts. The present invention furthermore includes all solvates of compounds of the formula I, for 25 example hydrates or adducts with alcohols. The invention also includes derivatives and modifications of the compounds of the formula 1, for example prodrugs, protected forms and other physiologically tolerable 30 derivatives, as well as active metabolites of the compounds of the formula I. The invention relates in particular to prodrugs and protected forms of the compounds of the formula I which can be converted into compounds of the formula I under physiological conditions. Suitable prodrugs for the compounds of the formula I, i. e. chemically modified derivatives of the compounds of the formula I having properties which are improved in a desired manner, for example with respect to solubility, bioavailability or duration of action, are known to those skilled in the art. More detailed information relating to prodrugs is found in standard literature like, for example. Design of Prodrugs, H. Bundgaard (ed.), Elsevier, 1985,, Fleisheret 5 al.. Advanced Drug Delivery Reviews 19 (1996) 115-130; orH. Bundgaard, Drugs of the Future 16 [1991) 443 which are all incorporated herein by reference. Suitable prodrugs for the compounds of the formula I are especially acyl prodrugs and carbamate prodrugs of acylatable nitrogen-containing groups such as amino groups and the guanidino group and also ester prodrugs and amide prodrugs of carboxylic acid groups which may be present in compounds of 10 the formula I. In the acyl prodrugs and carbamate prodrugs one or more, for example one or two, hydrogen atoms on nitrogen atoms in such groups are replaced with an acyl group or a carbamate, preferably a (CT-C1-alkyloxycarbonyl group. Suitable acyl groups and carbamate groups for acyl prodrugs and carbamate prodrugs are, for example, the groups RP1-CO- and Rp1o-CO-, in which RP1 is hydrogen, (Ci-Cisj-alkyI, (Ca-Gj-cydoalkyl, (C3-Ca)-cycloalkyl-{CrC,}-15 alkyl-, (G-Ci4)-aryl, Het-, (C6-CK)-aryl-(CrCt)-alkyl- or Het-[CrC4)-aIkyl- and in which RP1 has the meanings indicated for RP1 with the exception of hydrogen. Especially preferred compounds of the formula I are those wherein two or more residues are defined as indicated before for preferred compounds of the formula I, or residues can have 20 one or some of the specific denotations of the residues given in their general definitions or in the definitions of preferred compounds before. Ail possible combinations of definitions given for preferred definitions and of specific denotations of residues explicitly are a subject of the present invention. 25 Also with respect to all preferred compoundsof the formula 1 all their stereoisomeric forms and mixtures thereof in any ratio and their physiologically acceptable salts explicitly are a subject of the present invention, as well as are their prodrugs. Similarly, also in all preferred compounds of the formula I all residues that are present more than one time in the molecule are independent of each other and can be identical or different. 30 The compounds of the formula 1 can be prepared by utilizing procedures and techniques, which per se are well known and appreciated by one of ordinary skill in the art. Starting materials or building blocks for use in the general synthetic procedures that can be applied in the preparation of the compounds of formula I are readily available to one of ordinary skill in the art. In many cases they are commercially available or have been described in the literature. Otherwise they can be prepared from readily available precursor compounds 5 analogously to procedures described in the literature, or by procedures or analogously to procedures described in this application. In general, compounds of the formula I can be prepared, for example in the course of a convergent synthesis, by linking two or more fragments which can be derived retrosynthetically 10 from the formula I. More specifically, suitably substituted starting indole derivatives are employed as building blocks in the preparation of the compounds of formula I. if not commercially available, such indole derivatives can be prepared according to the well-known standard procedures for the formation of the indole ring system such as, for example, the Fischer indole synthesis, the Madelung indole synthesis, the indole synthesis starting from N- 15 chloroanilines and B-ketosuIfides described by Gassman et al., the Bischier indole synthesis, the Reissert indole synthesis, or the Nenitzescu indole synthesis. By choosing suitable precursor molecules, these indole syntheses allow the introduction of a variety of substituents into the various positions of the indole system which can then be chemically modified in order to finally arrive at the molecule of the formula I having the desired substituent pattern. As one of 20 the comprehensive reviews in which numerous details and literature references on the chemistry of indoles and on synthetic procedures for their preparation can be found, W. J. Houlihan (ed.),"Indoles, Part One", volume 25,1972, out of the series "The Chemistry of Heterocyclic Compounds", A. Weissberger and E. C Taylor (ed.), John Wiley & Sons, is referred to. 25 Examples of the many commercially available indole derivatives that are suitable as starting materials for the preparation of the compounds of formula I, are the following (the acids listed are commercially available as the free acids themselves and/or as the methyl or ethyl esters): indole-2-carboxylic acid, lndole-3-carboxylic acid, indole-3-acetic acid, 3-(3-indolyl)-propionic 30 acid, indole-2,3-dicarboxylic acid, 3-ethoxycarbonylmethyl-indole-2-carboxylic acid, 3-methyl-indole-2-car boxy lie acid, 5-fIuoroindole-2-carboxylic acid, 5-chloro-indole-2-carboxylic acid, 5-bromo-indole-2-carboxylic acid, 5-methoxy-indole-2-carboxylic acid, 5-hydroxy-indole-2- carboxylic acid, 5,6-dimethQxy-indo!e-2-carboxylic acid, 4-benzyloxy-indole-2-carboxylic acid, 5-benzyloxy-indole-2-carboxylic acid, 6-benzyloxy-5-methoxY-indole-2-carboxylic acid, 5-methyl-indole-2-carboxyiic acid, 5-ethyl-indole-2-carboxyiic acid, 7-methyl-indole-2-car boxy lie acid, 4-methoxy-indole-2-carboxylic acid, 6-methoxy-indole-2-carboxylic acid, 4,6-dimethoxy-5 indole-2-carboxylic acid, 4,6-dichloro-indole-2-carboxylic acid, 5-nitro-indole-2-carboxylic acid, 5-methylsulfonyl-indole-2-arboxylic acid, 7-nitro-indole-2-carboxyiic acid, 7-tert-butylcarbonyiam(no-indote-2-carboxyl!cacid, 7-(3-trifluoro-methyiben2oylamino)-indole-2-carboxyiic acid, 7-(4-methoxyphenylsulfonylamino)-indole-2-carboxylic acid, 5-bromo-3-methyl-indole-2 If starting indole derivatives are to be synthesized this can be done, for example, according to the well known indole syntheses mentioned above. In the following they are explained briefly, however, they are standard procedures comprehensively discussed in the literature, and are well known to one skilled in the art. 15 The Fischer indole synthesis comprises the acid cyclization of phenylhydrazones, for example of the general formula 2, 11N-N= ,304-1 R11 which can be obtained by various methods and in which R1', R1"" and R11and n can have a wide 20 variety of denotations. Besides hydrogen and alkyl, R11 and R11can especially denote ester groups or methyl or ethyl groups or 2,2,2- trifluoroethyl groups carrying an ester group as substituent thus allowing the introduction into the indole molecule of the (CHajp-CO moiety occurring in the groups R- and/or R1 in the compounds of the formula I. As examples of the many literature references describing the synthesis of indole derivatives according to the 25 Fischer synthesis, besides the above-mentioned book edited by Houlihan, the following articles are mentioned: F.G. Salituro et al.,J. Med. Chem. 33 (1990) 2944; N.M. Grayetal.,J. Med. Chem. 34 (1991) 1283; J. Sh. Chikvaidze et ai., Khim. Geterotsikl. Soedin. (1991) 1508; S. P. Hiremath et al., Indian J. Chem. 19 (1980) 770; J. Bornstein, J. Amer. Chem. See. 79 (1957) 1745; S. Wagaw, B.Yang and S. Buchwald, J. Am. Chem. Soc. 121 (1999)10251 orbyY. Murakami, Y. 30 Yokoyama, T. Miura, H.HirasawaY. Kamimura and M. Izaki, Heterocycles 22 (1984) 1211. The Reissert indole synthesis comprises the reductive cyclization of o-nitrophenylpyruvic acids or esters thereof, for example of the general formula 3, R'" CHj-CO-COOR1 NO; 5 in which the groups R1 can have a wide variety of denotations and can be present in all positions of the benzene ring. The Reissert indole synthesis leads to derivatives of indoIe-2-carboxylic acids. The pyruvic acid derivatives of the formula 3 can be obtained by condensation of oxalic acid esters with substituted o-nitrotoluenes. As literature references, besides the above-mentioned book edited by Houlihan and the literature articles mentioned 10 therein, for example the articles by H. G. Lindwall and G. J. Manteil, J. Org. Chem. 18 (1953) 345 or by H. Burton and j. L Stoves, J. Chem. Soc. (1937) 1726 or by W. Noland, F. Baude, Org. Synth Coil. Vol. V, J. Wiley, New York, (1973) 567 are mentioned. Another method to gain regioselective access to the indole structure involves palladium catalysis, for example o-haloanilines(X= CI, Br, I) or o-trlfluoromethanesufonyloxyanilines (X = 15 OTf) of the general formula 4 can be cyclized to indoles utilizing several alkynes by adopting procedures described by J. Ezquerra, C. Pedregal. C Lamas, J. Barluenga, M. Perez, M. Garcia-Martin, j. Gonzalez, J. Org. Chem. 61 (1996) 5805; or F. Uijainwalla, D. Warner, Tetrahedron Lett. 39 (1998) 5355 and furthermore A. Rodriguez, C Koradin, W. Dohle, P. Knochel, Angew. Chem. 112 (2000) 2607; or R. Larock, E. Yum, M. Refvik, J. Org. Chem. 63 (1998) 7653; R. Larock, 20 E. YumJ.Am. Chem. Soc. 113 (1991)6689; K. Roesch; R. Larock, J. Org. Chem. 66 (2001) 412 36 R1 R' 4 5 .6 Alternatively the indole structure can be built up by employment of a variety of ketones under palladium catalysis by adopting and modifying a procedure described byC Chen, D. Liebermann, R. Larsen, T. Verhoeven and P. Reider j. Org. Chem. 62 (1997) 2676 as indicated 25 below: 37 R X ,3a "-a 1 NHR1 O R 8 According to the Bischler indole synthesis V-ani!inoketones, for example of the general formula 10, ,40 O.-1R 1"-CX.T 11 N R 10 ,*2 R 5 can be cycllzed to indole derivatives. The Nenitzescu indole synthesis provides a valuable route to lndole-3-carboxyIic acid derivatives carrying a hydroxy group in the 5-position. It comprises the reaction of a para-benzoquinonewith a 3-aminocrotonate, for example of the compounds of the formulae 11 10 and 12. H11 X HjN COR Me 44 11 12 A further route to specifically substituted indole derivatives proceeds via 2,3-dihydroindoles (indolines) v/hich can be easily obtained by reduction of indoles, for example by hydrogenation, or by cyclization of suitable phenylethylamine derivatives. Indolines can 15 undergo a variety of electrophilic aromatic substitution reaction allovifjng the introduction of various substituents into the benzene nucleus which cannot directly be introduced by such reactions into the benzene nucleus of the indole molecule. The indolines can then be dehydrogenated to the corresponding indoles, for example with reagents like chloranil, or palladium together with a hydrogen acceptor. Again, details on these syntheses can be found 20 in the above-mentioned book edited by Houlihan. _ n 13 15 17 Moreover 2-H-indoies can be converted into the corresponding carboxylic acids or carboxylic esters by lithiation of the 2-posltion of the indoles of the general formula 13 and subsequent reaction with carton dioxide or alkytchioroformate according to I. Hasan, E. Mannelli, L Lin, F. 5 Fowler, A. Levy, ]. Org. Chem. 46 (1981) 157; T. Kline J. Heterocycl. Chem. 22 (1985} 505; J.-R. Dormoy, A. Heymes, Tetrahedron 49, (1993) 2885; E. Desarbre, S. Coudret, C. Meheust, J.-Y. Merour, Tetrahedron 53 (1997) 3637 as indicated below: R'1s denotes for Hydrogen or a protecting group like for example benzenesulfonyl or tert-10 butoxycarbonyl. Depending on the substituents In the starting materials, in certain indole syntheses mixtures of positional Isomers may be obtained which, however, can be separated by modern separation techniques like, for example, preparative HPLC 15 Further, in order to obtain the desired substituents in the benzene nucleus and in the heterocyclic nucleus of the indole ring system in the formula I, the functional groups introduced into the ring system during the indole synthesis can be chemically modified. For example, indoles carrying a hydrogen atom in the 2-po5ition or the 3-position can also be obtained by saponifiiiation and subsequent decarboxylation of indoles carrying an ester group 20 in the respective position. Carboxylic acid groups and acetic acid groups in the 2-position and the 3-position can be converted into their homologues by usual reactions for chain elongation of carboxylic acids. Halogen atoms can be introduced into the 2-position or the 3-position, for example by reacting the respeaive indolinone with a halogenating agent such as phosphorus pentachlorideanalogously to the method described by J. C. Powers,]. Org. Chem. 31 (1966) 25 2627. The starting Indolinones for such a synthesis can be obtained from 2-amtnophenyl acetic acids. Starting indole derivatives for the preparation of compounds of the formula I carrying a halogen substituent In the 3-position can also be obtained according to procedures described in the literature like the following. For the fluorination of 1 H-indole-2-carboxylic add ethyl ester derivatives in the 3-position N-fluoro-2,4,6-trimethylpyridinium triflate is the reagent of choice [T. Umemoto, S. Fukami, G. Tomizawa, K. Harasawa, K. Kawada, K. Tomita J. Am. Chem. Soc. 112(1990) 8563). Gilorination of IH-indole-Z-carboxylicacid ethyl ester derivatives in the 3-position by reaction with sulfuryf chloride in benzene yields 3-ch(oro-1 H-lndole-Z-carfaoxyfic 5 acid ethyl ester (Oiem. Abstr. 1%2, 3441i - 3442b); the same result can obtained by means of NCS (D. Comins, M. Killpack, Tetrahedron Lett. 33 (1989) 4337; M. Brennan, K. Erickson, F. Szmlac, M. Tansey, J. Thornton, Heterocycles 24 (1986) 2879). Bromination of 1H-indole-2-carboxylic acid ethyl ester derivatives in the 3-position can be achieved by reaction with NBS (M. Tani, H. Ikegami, M. Tashiro, T. Hiura, H. Tsukioka, Heterocycles 34 (1992) 2349). 10 Analogously to the procedures described above NIS can be used efficiently for the iodination in the of 1 H-indole-2-carboxYlic acid ethyl ester derivatives in the 3-position. Furthermore the iodination of 1 H-indole-2-carboxyiic acid ethyl ester derivatives in the 3-pQSition the use of iodine is efficient fT. Sakamoto, T. Nagano, Y. Kondo, H. Yamanaka Chem. Pharm. Bull. 36 (1988)2248). 15 Especially the groups present in the indole ring system can be modified by a variety of reactions and thus the desired residues R""1, R11 R1S R11 and Ri=be obtained. For example, nitro groups can be reduced to amino group with various reducing agents, such as sulfides, dithionites, complex hydrides or by catalytic hydrogenation. A reduction of a nitro group may also be carried out at a laterstageof the synthesis of a compound of the formula I, and a 20 reduction of a nitro group to an amino group may also occur simultaneously with a reaction performed on another functional group, for example when reacting a group like a cyano group 1-with hydrogen sulfide or when hydrogenating a group. In order to introduce or derive the residues R11"*, amino groups can then be modified according to standard procedures for alkylation, for example by reaction with (substituted) alkyl halogenides or by reductive 25 amination of carbonyl compounds, according to standard procedures for acylation, for example by reaction with activated carboxylic acid derivatives such as acid chlorides, anhydrides, activated esters or others or by reaction with carboxyfic acids in the presence of an activating agent, or according to standard procedures forsulfonylation, for example by reaction with sulfonyl chlorides. Carboxylic acids, carboxylic acid chlorides or carboxylic acid 30 esters can be introduced by procedures described by F. Santangelo, C Casagrande, G. Norcini, F. Gerli, Synth. Commun. 23 (1993)2717; P. Beswick, C. Greenwood, T. Mowlem, G. Nechvatal, D. Widdowson, Tetrahedron 44 (1988) 7325; V. Collot, M. Schmitt, P. Marwah, J. Bourguignon, Heterocylces 51 (1999) 2823. Halogens or hydroxy groups-via the triflate or nonaflate-or primary amines - via its diazonium salt - or after interconversion to the corresponding stannane, or boronic acid - present in the indole structure can be converted into a variety of other functional groups like for example -CN, -CFs, Ethers, adds, esters, amides, amines, alkyl-or aryl groups mediated by means of transition metals, namely palladium or nickel catalysts or 5 copper salts and reagents for example referred to below (F. Diederich, P. Stang, Metal-catalyzed Cross-coupling Reactions, Wiley-VCH, 1998; or M. Beller, C Bolm, Transition Metals for Organic Synthesis, Wiley-VCH, 1998; J. Tsuji, Palladium Reagents and Catalysts, Wiley, 1996; J. Hartwig, Angew. Chem. 110 (1998) 2154; B. Yang, S. Buchwald, j. Organomet. Chem. 576 (1999) 125; T. Sakamoto, K. Ohsawa, J. Chem. Soc. Perkin Trans 1, (1999), 2323; D. Nichols. S. Frescas, D. 10 Marona-Lewicka, X. Huang, B. Roth, G. Gudelsky, J. Nash, J. Med. Chem, 37 (1994), 4347; P. Lam, C. Clark, S. Saubern, j. Adams, M. Winters, D. Chan, A. Combs, Tetrahedron Lett., 39 (1998) 2941; D. Chan, K. Monaco, R. Wang, M. Winters, Tetrahedron Lett. 39 (1998) 2933; V. Farina, V. Krishnamurthy, W. Scott, The Stille Reaction. Wiley, 1994; A. Klaspars, X. Huang. S. Buchwald, J. Am. Chem. Soc. 124 (2002) 7421; F. Kwong, A. Klapars, S. Buchwald, Org. Lett. 4 (2002) 581; M 15 Wolter, G. Nordmann, G. job, S. Buchwald, 4 (2002) 973) Ester groups present in the benzene nucleus can be hydrolyzed to the corresponding carboxylic acids, which after activation can then be reacted with amines or alcohols under standard conditions. Ether groups present at the benzene nucleus, for example benzyloxy groups or 20 other easily cleavable ether groups, can be cleaved to give hydroxy groups which then can be reaaed with a variety of agents, for example etherification agents or activating agents allowing replacement of the hydroxy group by other groups. Sulfur-containing groups can be reacted analogously. 25 During the course of the synthesis in order to modify the groups R1 or R1'attached to the indole ring system by application of parallel synthesis methodology, beside a variety of reactions, palladium or copper salt catalysis can be extremely useful: Such reaaions are described for example in F. Diederich, P. Stang, Metal-catalyzed Cross-coupling Reactions, Wiley-VCH, 1998; or M. Beller, C. Bolm, Transition Metals for Organic Synthesis, Wiley-VCH, 30 1998; J. Tsuji, Palladium Reagents and Catalysts, Wiley, 1996; J. Hartwig, Angew. Chem. 110 (1998), 2154; B. Yang. S. Buchwald, J. Organomet. Chem. 576(1999)125; P. Lam, C Clark, S. Saubern, J. Adams, M. Winters, D. Chan, A. Combs, Tetrahedron Lett. 39 (1998) 2941; D. Chan, K. Monaco, R. Wang, M. Winters. Tetrahedron Lett. 39 (1998) 2933; j. Wolfe, H. Tomori, j. Sadight, J. Yin, S. Buchwald, j. Org. Chem. 65 [2000} 1158; V. Farina, V. Krishnamurthy, W. Scott, The Stille Reaction, Wiley, 1994; A. Klaspars, X. Huang, S. Buchwald, J. Am. Chem. Soc. 124 (2002) 7421; F. Kwong, A. Klapars. S. Buchwald, Org. Lett. 4 (2002) 581; M Woiter, G. Nordmann, G. Job, S. Buchwald, 4 (2002) 973). 5 The previously-mentioned reactions for the conversion of functional groups are furthermore, in general, extensively described in textbooks of organic chemistry like M. Smith, j, March, March's Advanced Organic Chemistry, Wiley-VCH, 2001 and in treatises like Houben-Weyl, "Methoden der Organischen Chemie" (Methods of Organic Chemistry), Georg Thieme Verlag, 10 Stuttgart, Germany, or "Organic Reactions", John Wiley & Sons, New York, or R. C Larock," Comprehensive Organic Transformations", Wiley-VCH, 2"'1 ed (1999), B. Trost, I. Fleming (eds.) Comprehensive Organic Synthesis, Pergamon,1991; A. Katritzky, C Rees, E. Scriven Comprehensive Heterocyclic Chemistry 11, Elsevier Science, 1996) in which details on the reactions and primary source literature can be found. Due to the fact that in the present case 15 the functional groups are attached to an indole ring It may in certain cases become necessary to specifically adapt reaction conditions or to choose specific reagents from a variety of reagents that can in principle be employed into a conversion reaaion, or otherwise to take specific measures for achieving a desired conversion, for example to use protection group techniques. However, finding out suitable reaction variants and reaction conditions in such 20 cases does not cause any problems for one skilled in the art. The structural elements present in the residues in the 1-position of the indole ring in the compounds of the formula 1 and in the COR1 group present in the 2-position and/or in the 3-positionof the indole ring can be introduced into the starting indole derivative obtainable as outlined above by consecutive reaction steps using parallel synthesis methodologies like those 25 outlines below using procedures which per se are well known to one skilled in the art. The residues R1" that can be introduced in formula 14, for example, by condensing a corresponding carboxylic acid of the formula 14 with a compound of the formula HR , i. e. with an annine of the formula HN(R1')R1'-V-G-M to give a compound of the formula 15. The 30 compound of the formula 15 thus obtained can already contain the desired final groups, i. e. the groups R1 and R1 can be the groups--N(R1)R1~V-G-M and R1-Q-as defined in the formula (, or optionally in the compound of the formula 15 thus obtained subsequently the residue or the residues R1 and the residue R1 are converted into the residues-N(R1)R1-V-G-M and R°-Q-, respectively, to give the desired compound of the formula I. R49 HRS' 14 formula I 15 Thus, the residues R1' and the residues R""' and R1'-V-G-M contained therein can have the 5 denotations of R"" and R1-V-G-M, respectively, given above or in addition in the residues R1' and R2'-V-G-M functional groups can also be present in the form of groups that can subsequently be transformed into the final groups R' and R1V-G-M, i. .e. functional groups can be present in the form of precursor groups or of derivatives, for example in protected form. In the course of the preparation of the compounds of the formula I it can generally be advantageous or 10 necessary to introduce functional groups which reduce or prevent undesired reactions or side reactions in the respective synthesis step, in the form of precursor groups which are later converted into the desired functional groups, or to temporarily block functional groups by a protective group strategy suited to the synthesis problem. Such strategies are well known to those skilled in the art (see, for example, Greene and Wuts, Protective Groups in Organic 15 Synthesis, Wiley, 1991, or P. Kocienski, Protecting Groups, Thieme 1994). As examples of precursor groups nitro groups and cyano groups may be mentioned which can in a later step be transformed into carboxylic acid derivatives or by reduction into aminomethy! groups, or nitro groups which may be transformed by reduction like catalytic hydrogenation into amino groups by redurtion. Protective groups can also have the meaning of a solid phase, and cleavage from the solid phase stands for the removal of the protective group. The use of such techniques is known to those skilled in the art [Burgess K (Ed.) Solid Phase Organic Synthesis ,New York: Wiley, 2000). For example, a phenolic hydroxy group can be attached to a trityl-poiystyrene resin, which serves as a protecting group, and the molecule is cleaved from this 5 resin by treatment with TFA at a later stage of the synthesis. The residue R™ in the compounds of the formulae 14 and 15 can denote the group -Q-R"as defined above which finally is to be present in the desired target molecule of the formula I, or it can denote a group which can subsequently be transformed into the group -Q-R°, for 10 example a precursor group or a derivative of the group -Q-R" in which functional groups are present in protected form, or R1o can denote a hydrogen atom or a protective group for the nitrogen atom of the Indole ring. Similarly, the residues Rl1 R11, Rl1 R1'1 and R1"* in the formulae 14 and 15 have the corresponding definitions of R1, R1, R1, R', and R1 in formula I as defined above, however, for the synthesis of the compounds of the formula I these residues, 15 too, can in principle be present at the stage of the condensation of a compound of the formula 14 with a compound of the formula HR1'giving a compound of the formula 15 in the form of precursor groups or in protected form. The residues R**1 in the compounds of the formula 14 which can be identical or different, can 20 be, for example, hydroxy or [G-C4)-alkoxy, i. e., the groups COR11 present in the compounds of the formula 14 can be, for example, the free carboxylic acids or esters thereof like alky! esters as can be the groups COR1 in the compounds of the formula I. The groups COR'1 can also be any other activated derivative of a carboxylic acid which allows amide formation, ester formation or thioester formation with a compound of the formula HR1'. The group COR'1 can 25 be, for example, an acid chloride, an activated ester like a substituted phenyl ester, an azolide like an imidazolide, an azide or a mixed anhydride, for example a mixed anhydride with a carbonic acid ester or with a sulfonic acid, which derivatives can all be prepared from the carboxylic acid by standard procedures and can be reacted with an amine, an alcohol or a mercaptan of the formula HRS' under standard conditions. A carboxylic acid group COOH 30 representing COR'*1 in a compound of the formula 14 can be obtained, for example, from an ester group introduced into the indole system during an indole synthesis by standard hydrolysis procedures. Compounds of the formula I in which a group COR1 is an ester group can also be prepared from compounds of the formula 14 in which COR't1 is a carboxylic acid group by common esterification reactions like, for example, reacting the acid with an alcohol under add catalysis, or alkyiation of a salt of the carboxyiic acid with an electrophile like an alkyl halogenide, or by 5 transesterifi cation from another ester. Compounds of the formula I in which a group COR1 is an amide group can be prepared from amines and compounds of the formula 14 in which COR'1 is a carboxylic acid group or an ester thereof by common amination reactions. Especially for the preparation of amides the compounds of the formula 14 in which COR11 is a carboxylic acid group can be condensed under standard conditions with compounds of the formula HR1' 10 which are amines by means of common coupling reagents used in peptide synthesis. Such coupling reagents are, for example, carbodiimides like dicyclohexylcarbodiimide (DCC) or diisopropylcarbodiimide, carbonyldiazoles like carbonyldiimldazole (CDI) and similar reagents, propylphosphonic anhydride, 0-((cyano-(ethoxycarbonyl)-methylene)amino)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TOTU), diethylphosphoryl cyanide (DEPC) or bis-(2-oxo- 15 3-oxa2olidinyl)-phosphoryl chloride (BOP-Cl) and many others. If the residue -Q-R° present in an indole of the formula I or the residue R1 present in an indole of the formula 14, or a residue in which functional groups within the residue-Q-R** or R1are present in protected form or in the form of a precursor group, have not already been 20 introduced during a preceding step, for example during a synthesis of the indole nucleus, these residues can, tor example, be introduced into the 1-position of the indole system by conventional literature procedures well known to one skilled in the art for N-alkyiation, reductive amination, N-aryiation, N-acylation or N-sulfony!ation of ring nitrogen atoms of heterocycles. The starting indole derivative that is to be employed in such a reaction carries a 25 hydrogen atom in the 1-position. N-Alkyiation of a ring nitrogen atom can, for example, be performed under standard conditions, preferably in the presence of a base, using an alkylating compound of the formula LG-Q-R1of of the formula R11-LG, wherein the atom in the group Q or in the group R1 bonded to the group LG in this case is an aliphatic carbon atom of an alkyl moiety and LG is a leaving group, for example halogen like chlorine, bromine or iodine, or a 30 sulfonyloxy group like tosyloxy, mesyloxy or trifluormethylsulfonyloxy. LG may, for example, also be a hydroxy group which, in order to achieve the alkyiation reaction, is activated by a conventional activating agent. For the preparation of compounds in which A is a direct linkage and an aromatic group is directly bonded to the 1-position of the indole system, conventional aryjation procedures can be used. For example aryl fluorides like alky! fluorobonzoates or 4-fluorophenyl methyl sulfones can be employed as arytating agents. Such processes are described, for example, By S. Stabler, Jahangir, Synth. Commun. 24 (1994) 123; 1. Khanna, R. Weier, Y. Yu, X. Xu. F. Koszyk, J. Med. Chem. 40 (1997) 1634. Alternatively a wide variety of substituted aryl iodides, aryl bromides or aryl triflates can serve as arylating agents at the 1-posttion of the indole system in a copper salt or palladium mediated reaction according to R. Sarges, H. Howard, tC Koe, A. Weissmann, J. Med. Chem, 32 (1989) 437; P. Unangst, D. Connor, R. Stabler, R- Weikert, J. Heterocyd. Chem, 24 (1987) 811; G. Tokmakov, I. Gr1ndberg, Tetrahedron 51 (1995)2091; D. Old, M. Harris. S. Buchwald, Org. Lett. 2 (2000) 1403, G. Mann, I J. Hartwig, M. Driver, C Fernandez-Rivas, J. Am. Chem. Soc. 120 (1998) 827; J. Hartwig, M. Kawatsura, S. Hauk, K. Shaughnessy, L. J. Org. Chem. 64 (1999) 5575. Moreover such arylations can also be accomplished by reaction of a wide range of substituted aryl faoronic acids as demonstrated for example by W. Mederski, M. Lefort, M. Germann, D. Kux, Tetrahedron 55 (1999) 12757. I In the course of the synthesis the employment of microwave assistance for speeding-up, facilitating or enabling reactions may be beneficial or even required in many cases. Some reactions are for example described by J. L. Krstenansky, I. Cotteril, Curr. Opin. Drug. Disc. & Development., 4(2000), 454; P. Lidstrom, J. Tierney, B. Wathey, j. Westman, Tetrahedron, ) 57(2001), 9225; M. Urhed, A. Hallberg, Drug Discovery Today, 8 (2001) 406; S. Caddick, Tetrahedron, 51 (1995) 10403. Preferred methods include, but are not limited to those described in the examples. 5 The compounds of the present invention are serine protease inhibitors, which Inhibit the artivity of the blood coagulation enzyme factors Xa and/or factor Vila. In particular, they are highly active inhibitors of factor Xa. They are specific serine protease inhibitors inasmuch as they do not substantially inhibit the activity of other proteases whose inhibition is not desired. The activity of the compounds of the formula I can be determined, for example, in the assays 0 described below or in other assays known to those skilled in the art. With respen to factor Xa inhibition, a preferred embodiment of the invention comprises compounds which have a Ki Q 1 for factor Xa inhibition as determined in the assay described below, with or without concomitant factor Vila inhibition, and which preferably do not substantially inhibit the activity of other proteases involved in coagulation and fibrinolysis whose inhibition is not desired (using the same concentration of the inhibitor). The compounds of the invention inhibit factor Xa catalytic activity either directly, within the prothrombinasecomplexorasa soluble subunit, or indirectly,.by inhibiting the assembly of factor Xa into the prothrombinase 5 complex. The present invention also relates to the compounds of the formula I and/or their physiologically tolerable salts and/or their prodrugs for use as pharmaceuticals (or medicaments), to the use of the compounds of the formula i and/or their physiologically 10 tolerable salts and/or their prodrugs for the production of pharmaceuticals for inhibition of factor Xa and/or factor Vila or for influencing blood coagulation, inflammatory response or fibrinolysis or for the therapy or prophylaxis of the diseases mentioned above or below, for example for the production of pharmaceuticals for the therapy and prophylaxis of cardiovascular disorders, thromboembolic diseases or restenoses. The invention also relates to 15 the use of the compounds of the formula I and/or their physiologically tolerable salts and/or their prodrugs for the inhibition of factor Xa and/or factor Vila or for influencing blood coagulation or fibrinolysis or for the therapy or prophylaxis of the diseases mentioned above or below, for example for use in the therapy and prophylaxis of cardiovascular disorders, thromboembolic diseases or restenoses, and to methods of treatment aiming at such purposes 20 including methods for said therapies and prophylaxis. The present invention also relates to pharmaceutical preparations (or pharmaceutical compositions) which contain an effective amount of at least one compound of the formula I and/or its physiologically tolerable salts and/or its prodrugs in addition to a customary pharmaceutically acceptable carrier, i. e. one or more pharmaceutically acceptable carrier substances or excipients and/or auxiliary substances 25 or additives. The invention also relates to the treatment of disease states such as abnormal thrombus formation, acute myocardial infarction, unstable angina, thromboembolism, acute vessel closure associated with thrombolytic therapy or percutaneous transluminal coronary 30 angioplasty, transient ischemic attacks, stroke, pathologic thrombus formation occurring in the veins of the lower extremities following abdominal, knee and hip surgery, a risk of pulmonary thromboembolism, or disseminated systemic intravascular coagulatopathy occurring in vascular systems during septic shock, certain viral infections creancer. The compounds of the formula 1 and their physiologically tolerable salts and their prodrugs can be administered to animals, preferably to mammals, and in particular to humans as pharmaceuticals for therapy or prophylaxis. They can be administered on their own, or in 5 mixtures with one another or in the form of pharmaceutical preparations which permit entera or parenteral administration. The pharmaceuticals can be administered orally, for example in the form of pills, tablets, lacquered tablets, coated tablets, granules, hard and soft gelatin capsules, solutions, syrups, 10 emulsions, suspensions or aerosol mixtures. Administration, however, can also be carried out rectally, for example in the form of suppositories, or parenterally, for example intravenously, intramuscularly or subcutaneously, in the form of injection solutions or infusion solutions, microcapsules, implants or rods, or percutaneously or topically, for example in the form of ointments, solutions or tinctures, or in other ways, for example In the form of aerosols or nasal 15 sprays. The pharmaceutical preparations according to the invention are prepared in a manner known perse and familiar to one skilled in the art, pharmaceutically acceptable inert inorganic and/or organic carriers being used in addition to the compound(s) of the formula I and/or its (their) physiologically tolerable salts and/or its (their) prodrugs. Forthe production of pills, 20 tablets, coated tablets and hard gelatin capsules it is possible to use, for example, lactose, cornstarch or derivatives thereof, talc, stearic acid or its salts, etc. Carriers for soft gelatin capsules and suppositories are, for example, fats, waxes, semisolid and liquid polyols, natural or hardened oils, etc. Suitable carriers for the production of solutions, for example injection solutions, or of emulsions or syrups are, for example, water, saline, alcohols, glycerol, polyols, 25 sucrose, invert sugar, glucose, vegetable oils, etc. Suitable carriers for microcapsules, implants or rods are, for example, copolymers of glycolic acid and lactic acid. The pharmaceutical preparations normally contain about 0.5 % to 90 % by weight of the compounds of the formula \ andiof their physiologically tolerable salts and/or their prodrugs. The amount di the active ingredient of the formula 1 and/or its physiologically tolerable salts and/or its prodrugs in the 30 pharmaceutical preparations normally is from about 0.5 mg to about 1000 mg, preferably from about 1 mg to about 500 mg. in addition to the active ingredients of the formula I and/or their physiologically acceptable salts and/or prodrugs and to carrier substances, the pharmaceutical preparations can contain additives such as, for example, fillers, disintegrants, binders, lubricants, wetting agents, stabilizers, emulsifiers, preservatives, sweeteners, colorants, flavorings, aromatizers, 5 thickeners, diluents, buffer substances, solvents, solubiiizers, agents for achieving a depot effect, salts for altering the osmotic pressure, coating agents or antioxidants. They can also contain two or more compounds of the formula I and/or their physiologically tolerable salts and/or their prodrugs. In case a pharmaceutical preparation contains two or more compounds of the formula t the selection of the individual compounds can aim at a specific overall 10 pharmacological profile of the pharmaceutical preparation. For example, a highly potent compound with a shorter duration of action may be combined with a long-acting compound of lower potency. The flexibility permitted with respect to the choice of substituents in the compounds of the formula I allows a great deal of control over the biological and physico-chemical properties of the compounds and thus allows the selection of such desired 15 compounds. Furthermore, in addition to at least one compound of the formula I and/or its physiologically tolerable salts and/or its prodrugs, the pharmaceutical preparations can also contain one or more other therapeutically or prophylactically active ingredients. As inhibitors of factor Xa and/or factor Vita the compounds of the formula I and their 20 physiologically tolerable salts and their prodrugs are generally suitable for the therapy and prophylaxis of conditions in which the activity of factor Xa and/or factor Vila plays a role or has an undesired extent, or which can favorably be influenced by inhibiting factor Xa and/or factor Vila or decreasing their activities, or for the prevention, alleviation or cure of which an inhibition of factor Xa and/or factor Vila or a decrease in their activity is desired by the 25 physician. As inhibition of factor Xa and/or factor VI la influences blood coagulation and , fibrinolysis, the compounds of the formula I and their physiologically tolerable salts and their prodrugs are generally suitable for reducing blood clotting, or for the therapy and prophylaxis of conditions in which the activity of the blood coagulation system plays a role or has an undesired extent, or which can favorably be influenced by reducing blood clotting, or for the 30 prevention, alleviation or cure of which a decreased activity of the blood coagulation system is desired by the physician. A specific subject of the present invention thus are the reduction or inhibition of unwanted blood clotting, in particular in an individual, by administering an effective amount of a compound I or a physiologically tolerable salt or a prodrug thereof, as well as pharmaceutical preparations therefor. Conditions in which a compound of the formula I can be favorably used include, for example, 5 cardiovascular disorders, thromboembolic diseases or complications associated, for example, with infection or surgery. The compounds of the present invention can also be used to reduce an inflammatory response. Examples of specific disorders for the treatment or prophylaxis of which the compounds of the formula I can be used are coronary heart disease, myocardial infarction, angina pectoris, vascular restenosis, for example restenosis following angioplasty 10 like PICA, adult respiratory distress syndrome, multinargan failure, stroke and disseminated intravascular clotting disorder. Examples of related complications associated with surgery are thromboses like deep vein and proximal vein thrombosis, which can occur following surgery. In view of their pharmacological activity the compounds of the invention can replace or supplement other anticoagulant agents such as heparin. The use of a compound of the 15 invention can result, for example, in a cost saving as compared to other anticoagulants. When using the compounds of the formula I the dose can vary within wide limits and, as is customary and is known to the physician, is to be suited to the individual conditions in each individual case. It depends, for example, on the specific compound employed, on the nature and severity of the disease to be treated, on the mode and the schedule of administration, or 20 on whether an acute or chronic condition is treated or whether prophylaxis is carried out. An appropriate dosage can be established using clinical approaches well known in the medical art. in general, the daily dose for achieving the desired results in an adult weighing about 75 kg is from 0.01 mg/kgtolOO mg/kg. preferably from 0.1 mg/kgto 50 mg/kg, in particular from 0.1 mg/kg to 10 mg/kg, (in each case in mg per kg of body weight). The daily dose can be 25 divided, in particular in the case of the administration of relatively large amounts, into several, for example 2, 3 or 4, part administrations. As usual, depending on individual behavior it may be necessary to deviate upwards or downwards from the daily dose indicated. A compound of the formula I can also advantageously be used as an anticoagulant outside an 30 individual. For example, an effective amount of a compound of the invention can be contacted with a freshly drawn blood sample to prevent coagulation of the blood sample. Further, a compound of the formula t and its salts can be used for diagnostic purposes, for example in in vitro diagnoses, and as an auxiliary in biochemical investigations. For example, a compound of the formula I can be used in an assay to identify the presence of factor Xa and/or factor Vila or to isolate factor Xa and/or factor Vila in a substantially purified form. A compound of the invention can be labeled with, for example, a radioisotope, and the labeled compound bound to factor Xa and/or factor Vila is then detected using a routine method useful for detecting the 5 particular label. Thus, a compound of the formula I or a salt thereof can be used as a probe to detect the location or amount of factor Xa and/or factor Vila activity in vivo, in vitro or ex vivo. Furthermore, the compounds of the formula I can be used as synthesis intermediates for the preparation of other compounds, in particular of other pharmaceutical active ingredients, 10 which are obtainable from the compounds of the formula I, for example by introduction of substituents or modification of functional groups. The general synthetic sequences for preparing the compounds useful in the present invention our outlined in the examples given below. Both an explanation of, and the actual procedure 15 for, the various aspects of the present invention are described where appropriate. The following examples are intended to be merely illustrative of the present invention, and not limiting thereof in either scope or spirit. Those with skill in the art will readily understand that known variations of the conditions and processes described in the examples can be used to synthesize the compounds of the present invention. 20 It is understood that changes that do not substantially affect the activity of the various embodiments of this invention are included within the invention disclosed herein. Thus, the following examples are intended to illustrate but not limit the present invention. 25 Examples When in the final step of the synthesis of a compound an acid such as trifluoroacetic acid or acetic acid was used, for example when trifluoroacetic acid was employed to remove a tBu group or when a compound was purified by chromatography using an eluent which contained 30 such an acid, in some cases, depending on the work-up procedure, for example the details of a freeze-drying process, the compound was obtained partially or completely in the form of a salt of the acid used, for example in the form of the acetic acid salt or trifluoroacetic acid salt or hydrochloric add salt Abbreviations used: tert-Buty! tBu 2,2'-bis(diphenyiphoshino-1,1 '-binaphthyl Binap 5 Bis-(oxo-3-oxazolidinyl}-phosphoryl chloride dibenzylidenacetone dba Dicyclohexyl-carbodiimide DCC Dichioromethane DCM Di ethyl phosp ho ryl cyanide DEPC 10 4-Dimethyaminopyridine DMAP N,N-Oimethylformamide DMF Dimethy [sulfoxide DM SO Ethyl-diisopropyl-amine DIPEA 1,1'-Bis(diphenylphDsphino)ferrocene 15 0-(7-A2aben20tr!a2ol-1-yi)-N,N,N',N'-tetramethyluronium- H exaf 1 u 0 rop hos p h ate HATU N-Bromosuccinimide NBS N-Chlorosuccinimide NCS N-Iodosuccinimide NIS 20 N-Ethylmorpholine NEM Methanol MeOH Room temperature RT Tetrahydrofuran THE Trifluoroaceticacid TEA 25 0-((Ethoxycarbonyl)cyanomethyleneamino)- N,N,N',N'-tetramethyluronium tetrafluoroborate TOTU BOP-0 DPPF '1.- Example 1: 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-yimethyl]-lH-indole-2-carboxYlic acid (1-30 !Sopropyl-piperidin-4-yl)-amide (i) (1-lsopropyl-pJperidin-4-yl)-carbam!c acid tert-buty! ester N o b1 To a solution of 5.0 g Piperldin-4-yl-carbamic acid tert-butyl ester in 15 ml methanol, 7.34 ml 5 acetone, 3.14 g Na(CN)BH3 and 0.3 ml acetic acid were added. After stirring for T 6h at room temperature the solvent was removed under reduced pressure and the residue was partitioned between 30 nnl of water and 30 ml ethyl acetate. The organic layer was washed with saturated NazCOj solution, water and then dried over Na2S04. The solvent was removed under reduced pressure to give the product as a white solid- Yield: 4.8g M5(E5+): m/e=243. 10 (ii) 1-lsopropyl-piperidin1-ylamine H1N N J To 4.8 g [1-lsopropyl-piperidin-4-yl)-carbamicacid tert-butyl ester in 15 ml methanol, 20 ml methanollc hydrochloric acid (8M) were added and the mixture was stirred for 16h. Removal of 15 the solvent under reduced pressure, followed by removal of residual volatiles by twice coevaporating with toluene, gave the product. Yield: 5.42 g MS(B+):m/e=143. (iii) 1H-indole-2-carboxylic acid methyl ester 2 g of 1 H-lndole-2-carboxylic acid was dissolved in 15 m! of methanolic hydrochloric acid (8Mj 20 and the mixture was stirred at RTfor 16h. After removal of the solvent under reduced pressure, reisidual volatiles were removed by codistillation twice with 10 ml toluene. The remaining slightly yellow solid was subjected to the subsequent reaction without further purification. Yield: 2.3g (iv) l-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indoie-2-carboxylicacid methyl ester O — CI To a solution of244.2mg1H-lndoie-2-carboxylic acid methyl ester in 2 ml DMF, 52.2 mg sodium hydride (60% in oil) were added at RT. After stirring for 30 min 500 mg 3-5 Bromomethyl-5-(5-chloro-thiophen-2-yi)-iso)razole [prepared by adopting a procedure described by Ewing, William R.; Becker, Michael R.; Choi-Sledeski, Yong Mi; Pauls, Heinz W.; He, Wei; Condon, Stephen M.; Davis, Roderick 5.; Hanney, Barbara A.; Spada, Alfred P.; Burns, Christopher J.; Jiang, John Z.; Li, Aiwen; Myers, Michael R.; Lau, Wan F.; Poll, Gregory B; PCT Int. Appl. (2001), 460 pp. WO 0107436 A2] were added and the mixture was heated for 1h at 10 80°C After subsequent cooling of the reaction to RT and addition of 5 ml water the mixture was filtered through a chem elut® cartridge by elution with ethyl acetate. After concentration under reduced pressure the residue was directly subjected to the subsequent saponification reaction without further purification. Yield: 288 mg MS (ES+)-. m/e= 373. 15 (v) 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxYlIcacid To a solution of 288 mg 1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1 H-indole-2-carboxyiic acid methyl ester in 10 miTHF, 3 ml water and 57.0 mg lithium hydroxide monohydrate were added. After stirring for 2 h at 60°C the reaction was cooled to RT. The 20 mixture was acidified with half concentrated hydrochloric acid. The resulting precipitate was collected by filtration and washed with 3 ml water. The product was obtained as a white solid which was dried under reduced pressure. Yield: 253 mg MS (ES+): m/e= 359, chloro pattern. 25 (vi) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indo[e-2-carboxylic acid [1- isopropyl-piperidin-4-yl}-amide To a solution of 117 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid in 1 ml DCM and 0.17 ml NEtj ,76 mg BOP-CI were added at RT and the mixture A solution of 3 g Piperidin-4-yl diluted with DCM and was washed with NaHCOs solution and then with water. The organic layer was dried over Na2S04 and the solvent was removed under reduced pressure. 5 Chromatographic purification of the residue on silica gel with DCM as eluent gave after evaporation of the fractions containing the product a white foam. Yield 1.7 g. {ii)3,4,5,6-Tetrahydro-2H-[1,4']bipyridinyl-4-y!amine 10 To a solution of 4 g (3,4,5,6-Tetrahydro-2H-[1,4']bipyridinyl4-yl)-carbamic acid tert-butyl ester In 4 ml DCM, 12 ml TFA was added at RT. After stirring for 20 h the solution was diluted with 20 ml of toluene and was evaporated under reduced pressure. The residue was codlstilled twice with toluene and was used in the subsequent reactions without further purification. The product was obtained as its trifluoroacetate salt. 15 Yield: 2.7 g. (iii) 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1H-indole-2-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4']blpyridinyl-4-yl)-amide The title compound was prepared analogously to example 1 with the difference that 3,4,5,6-20 Tetrahydro-2H-[1,4']bipyridiny!-4-ylamine was used instead of l-tsopropyl-piperidin-4-ylamine. MS (ESI+): m/e ^ 518, chloro pattern. Example 29: 1-[5-(5-Chloro-thiophen-2-Yl)-isoxazol-3-y!methyl]-7-methyl-1H-indole-2- carboxylicacid (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide \\ 25 The title compound was prepared analogously to example 28 with the differerice that 7-Methyl-lH-indoie-2-carboxylic acid was used instead of 1H-lndQle-2-carboxylic acid. MS (ESI+}: m/e = 532, chloro pattern. Example 30: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-nitro-1H-indole-2-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide 5 The title compound was prepared analogously to example 28 with the difference that 5-Nitro- 1H-indole-2-carboxylicadd was used instead of 1H-lndole-2-carboxylic acid. MS (ESI+): m/e = 563, chloro pattern. 10 Example 31: {1-[5-(5-Ch!oro-thiophen-2-Yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-[4-(pyridin-4-ylamino}-piperidin-1-yl]-methanone (i} 4-(Pyridin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester ^^^ ^M^^ 15 A solution of 2.5 g 4-Amino-piperidine-l-carboxylic acid tert-butyl ester and 2.5 g 4- chloropyridine in 9 ml n-butanol/water/NEt31:1:1 was heated at 100 °Cfor85 h.Then the solution was cooled to RT was diluted with DCM and was washed with NaHCCb solution and water. The organic layer was dried over Na2S04 and the solvent was removed under reduced 20 pressure. Chromatographic purification of the residue on silica gel with DCM as eluent gave after evaporation of the fractions containing the product, a white foam. Yield 1.7 g. (ii) Plperidin-4-yl-pyridin-4-yi-amine N ^N- To a solution of 1.7 4-(Pyridin-4-ylamino}-piperidine-1- (iii) {1-[5-(5-Chloro-thiophen-2-y|}-isoxazol-3-ylmethyl]-1 H-indol-2-yl}-[4-(pyrldin-4- ylamino)-10 piperidtn-Vyl]-methanone The title compound was prepared analogously to example 1 with the difference that Piperidin-4-yl-pyridin-4-yl-amine was used instead of l-lsopropyl-piperidin-4-ylamine. MS (ESU-): m/e = 518, chloro pattern. 15 Example 32: {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-Ylmethyl]-5-nitro-1H-indol-2-yl}-[4- (pyridin-4-ylamina)-piperidin-l-yl]-methanone The title compound was prepared analogously to example 31 with the difference that 5-Nitro-1 H-indole-2-carboxylic acid was used instead of 1 H-lndole-2-carboxylic acid. 20 MS [ES1+): m/e = 563, chloro pattern. Example 33: {1-[5-(5-Chloro-thfophen-2-yl)-isoxazol-3-ylmethyf]-7-methyl-1H-indoI-2-yl}-[4-(pyridin- 4-ylamino)-piperidin-l-yl]-methanone The title compound was prepared analogously to example 31 with the difference that 7-Methyi-1 H-Jndole-2-carboxylic acid was used instead of 1 H-lndole-2-carboxy(ic acid. MS {ESI+): m/e = 532. chloro pattern. Example 34: {1-[5-(5'Chloro-thiophen-2-yl)-isoxazol-3-Ylmethyl]-l H-indDl-2-ylH4-isopropYlamino- piperidin-1-yl)-methanone 10 (1) 4-lsopropylamino-piperidine-1-carboxYlic acid tert-butyl ester VN o -o To a solution of 1.5 g4-Amino-piperidine-1-carboxylicacid tert-butyl ester in 20 ml acetonitrile, 2.6 ml acetone, 0.94 g Na[CN)BH3 and 0.3 ml acetic acid were added. After stirring for T6h at RT the solvent was removed under reduced pressure and the residue was partitioned 15 between 30 mi of water and 30 ml of ethyi acetate. The organic layer was washed with saturated NazCOs solution, water and was dried over NazSO^. Removal oi the solvent under reduced pressure yields a white solid. Yield: 2.8 g MS (ES"*"): m/e- 243. (ij) lsopropyl-piperidin-4-yl-amine HN 20 To a solution of 2.8 g 4-lsopropylamino-piperidine-1-carboxylic acid tert-butyl ester in 8 ml DCM,4 ml TFA was added at RT. After stirring for 20 h the solution was diluted with 20 ml of toluene and was evaporated under reduced pressure. The residue was codistiiled twice with toluene and was used in the subsequent reactions without further purification. The product was obtained as its trjfluoroacetate salt. Yield: 4.4 g MS (ES+): m/e= 143: 5 (iii) {1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethy!]-1 H-indol-2-yl}-(4-isopropy|amino- piperidin-1-yl)-methanone The title compound was prepared analogously to example 1 with the difference that Isopropyl- piperidin-4-yl-amine was used instead of 1-isopropyl-piperidin4-ylamine. MS (ESI+): m/e = 483, chloro pattern. 10 Example 35: {1-[5-(5-Chloro-thiophen-2-yl)-isoxa2oi-3-ylmethyl]-7-methy!-1H-indol-2-ylH4- isopropylamino-piperidin-1-yi)-methanone The title compound was prepared analogously to example 34 with the difference that 7-Methyl-1H-indole-2-carboxylicacid was used instead of 1H-lndole-2-carboxylicacid. 15 MS (ESI+): m/e = 497, chloro pattern. Example 36:1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid (1-ethyl- piperidin-4-yl)-amide CXK 20 (i) (l-Ethyl-piperidIn-4-yl)-carbamicacid tert-buty! ester N— To a solution of 5 g Piperidin-4-yl-carbamic acid tert-butyl ester in 20 ml methanol, 5.6 ml acetaldehyde. 3.2 g Na{CN)BH3 and 32 g acetic acid were added. After stirring for 16h at RT the solvent was removed under reduced pressure and the residue was partitioned between 30 ml of water and 200 ml of ethyl acetate. The organic layer was washed with saturated NajCOa 5 solution, water and then it was dried over Na2S04. Removal of the solvent under reduced pressure gave a white solid. Yield: 4.4 g. (il) 1-Ethy!-ptperidin-4-ylamine N- HjN 20 To4.4g(1-£thyl-piperidin-4-yJ}-carbam(cacid tert-butyl ester in 15 m) methanol, 20 ml of methanolic hydrochloric acid (8M) was added and the mixture was stirred for16h. Removal of the solvent under reduced pressure gave a white solid, which was coevaporated twice with 20 mi toluene. The product was obtained as its hydrochloride. Yield: 4.3 g. 15 (iii) 1-[5-{5-Chioro-thiophen-2-yl)-isoxa2ol-3-yimethyl]-1 H-indole-2-carboxylic acid {1-ethyl- piperidin-4-yl)-amide The title compound was prepared analogously to example 1 with the difference that 1-Ethyl- piperidin-4-ylamine was used instead of 1-lsopropyl-piperidin-4-yiamine. 20 US (ESH-): m/e = 469, chloro pattern. 25 Example 37:1-[5-(5-Chloro-thiophen-:^-Yl)-isoxazol-3-y!methyl]-7-methyl-1H-indole-2-carboxylic acid {1-ethYl-piperidin-4-yl}-amide .0 The title compound was prepared analogously to example 36 with the difference that 7-methyl-1H-indo!e-2-carboxylic acid was used instead of 1H-lndole-2-carboxylic acid. MS (ES1+): m/e = 483, chloro pattern. Example 38:-{T-[5-{5-Chloro-thiophen-2-yi}-isoxa2oi-3-yimethyl]-1H-indol-2-ylH4-pvrro!idin-1-5 yl-piperidin-1-yi)-methanone .0 The title compound was prepared analogously to example 1 with the difference that 4-Pyrrolidin-1-yt-piperidine was used instead of 1-lsopropyl-piperidin-4-ylamine. 10 MS (ESI+): mk = 509, chloro pattern. Example 39: {1-[5-(5-Chloro-th!ophen-2-yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-[4-(1-methyl-piperidin-4-y[)-piperazin-1-yl]-methanone 15 The title compound was prepared analogously to example 1 with the difference that 1-(1- Methyl-piperidin-4-yl)-piperazine was used instead of 1-lsopropyl-piperidin-4-y|amine. MS (ESI+): m/e ^ 524, chloro pattern. 20 Example 40: [1,4']Bipiperidinyl-1'-yl-{1-[5-(5-chloro-thiophen-2-yl}-isoxazDl-3-ylmethyl]-1H-jndol- 2-yl}-methanone The title compound was prepared analogousfy to example 1 with the difference that [1,4']biplperidinyl was used instead of 1-lsopropyl-piperidin-4-ylamine. 5 MS (ESIH-): m/e = 523, chloro pattern. Example 41:1-[5-(5-Chloro-thiophen-2-yl)-isoxazo!-3-ylmethyl]-1H-indole-2-carboxylic acid (3-pyridin-4-yl-4,5-dihydro-i5oxazol-5-ylmethyl)-amide N 10 . Ci The title compound was prepared analogousiy to example 1 with the difference that C-(3- Pyridin-4-yl-4,5-dihydro-isoxazol-5-yl)-methy[amine was used instead of 1-lsopropyl-piperidin- 4-ylamlne. MS (ESI+): m/e = 518, chloro pattern. 15 Example 42: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxy!ic acid (4-amino- quinazolin-7-ylmethyl)-amide a>^: The title compound was prepared analogously to example 1 with the difference that 7-AmJnomethyl-quinazolin-4-ylamine [Ewing, William R. et al. PCT Int. Appl. (2001), 460 pp. WO 0107436 A2] was used instead of 1-lsopropyl-piperidin-4-ylamine. 5 MS [ESi+):m/e = 515. chloro pattern. Example 43: {1-[5-(5-Chloro-thiophen-2-yl)-i50xazol-3-ylmethyl]-1H-!ndol-2-yl}-(4-pyridin-4-ylmethyl-plperazin-1-yl)-methanone Cl, v-s LO The title compound was prepared analogously to example 1 with the difference that 1-Pyridin-4-ylmethyl-piperazine was used instead of 1-lsopropYl-piperidin-4-ylamine. MS (E5I+): m/e = 518, chloro pattern. 15 Example 44: l-[5-(5-Chloro-thiophen-2-Yl)-i50xazol-3-ylmethyl]-1H-indole-2-carboxylic acid 3,5-dichloro-benzylamide The title compound was prepared analogously to example 1 with the difference that 3,5-Dichloro-benzyiamine was used instead of 1-isopropyl-piperidin-4-ylamine. MS (ESI+}: m/e = 516, chloro pattern. Example45:1-[5-{5-Chloro-thiophen-2-yt)-isoxazo!-3-ylmethyi]-1H-indole-2-carboxyiicacid(4-tert-butyI-phenyJ)-a m ide The title compound was prepared analogously to example 1 with the difference that 4-tert-10 Butyl-phenylamine was used instead of l-isopropyl-piperidin^-ylamine. MS (ESH): m/e = 490, chloro pattern. Example 45:1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indole-2-carboxylic acid {1-15 isopropyl-piperidin-4-ylmethyl)-amide (i) (l-lsopropyl-piperidin^-yimethyl)-carbamic acid tert-butyl ester n o -o To a solution of T.O g Piperidin-4-ylmethyl-carbamic acid tert-butyl ester in 20 mi acetonitrile, 20 2.6 ml acetone and 586 mg Na(CN}BH3 were added. After stirring for 16h at RT the solvent was removed under reduced pressure and the residue was partitioned between 30 ml of water and 30 ml of ethyl acetate. The organic layer was washed with saturated NazCOs solution, water and was dried over NaiSO^. Removal of the solvent under reduced pressure gave a white solid. Yield: 802 mg. N 5 (ii) C-(1-lsopropyl-piperidin-4-yl)-methylamine H2N To a solution of 802 mg (1-lsopropyl-piperidin-4-yimethyl}-carbamic acid tert-butyl ester in 5 ml DCM,4 ml TFA was added at RT. After stirring for 20 h the solution was diluted with 20 ml of toluene and was evaporated under reduced pressure. The residue was codistilled twice with 10 toluene and was used in the subsequent reactions without further purification. The product was obtained asitstrifluoroacetatesalt. Yield: 1.7 g (iii) l-[5-(5-Chloro-thiophen-2-vl}-isoxazol-3-ylmethyl]-T H-indole-2-carboxylic acid {^- isopropyi- piperidin-4-yImethyl}-amide The title compound was prepared analogously to example 1 with the difference that C-(1-15 lsopropyl-piperidin-4-yl)-methylamInewas used instead of 1-lsopropYl-piperidin-4-ylamine. MS [ESi+): m/e = 496, chloro pattern. Example 47:1-[5-(5-Chloro-thiophen-2-yl}-isoxa2ol-3-ylmethylj-lH-indole-2-carboxyiic acid 20 (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-ylmethyl)-amide N- s ~^ CI' (i) (3,4,5,6-Tetrahydro-2H-[l ,4']bipyridinyl-4-ylmethyl}-carbamic acid tBu ester ■ N* VN N A suspension of 5 g (23.3 mmol) Piperidin 4-ylmethyl-carbamic acid tBu ester 3.85 g (25.7 mmol) and 4-Chloropyridine hydrochloride in 15 ml n-BuOH/HzO/NEti 1:1:1 was boiled under reflux for 3 days. After removal of the solvent under reduced pressure the residue was purified by chromatography on silica gel with DCM/MeOH 100:1 -> 50:1 ->10:1 -5:1. The product was 5 obtained as a white solid. Yield: 4.3 g. (ii)C-{3,4,5,6-TetrahYdrD-2H-[1,4']bipyridinyl-4-yl}-methylamine To a solution of 4.58 g {3,4,5,&-Tetrahydro-2H-[1,4']bipyridinyl-4-ytmethyl}-carb3mic acid tBu 10 ester in 12 ml DCM, 12 ml TFA was added at RT. After stirring for 30 min the solution was diluted with 20 ml of toluene and was evaporated under reduced pressure. The residue was codistilled twice with toluene and was used in the subsequent reactions without further purification. The product was obtained as its trifluoroacetate salt. Yield: 3.3 g. 15 (ill) 1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid (3,4,5,6- tetrahydro-2H-[l,4']bipyridinyl^-ylmethYl)-amide The title compound was prepared analogously to example 1 with the difference that C-(3,4,5,6- TetrahydrQ-2H'[1,4']bipyridinyl-4-yl)-methyiaminewas used instead of 1-lsopropyl-piperidin-4- 20 ylamine. MS (ESI+): m/e = 532, chloro pattern. Example 48:1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1H-indole-2-<:arboxyl> o H H -C^- 25 (i) (1-Cyclopropyl-piperldin-4-yl}-carbamic acid tert-butyl ester o t N— To a suspension of 1 g Piperidin^-yl-carbamic acid tert-butyl ester, 2 g freshly activated 3 A molecular sieve, 1 mi acetic add, 6 ml 1- Ethoxycyclopropyl-oxy-trimethyls!lane in 25 ml methanol, 22.5 ml Na(CN)BH3(1M in THF) were added and the mixture was heated under 5 reflux for 2 h. The reaction mixture was filtered through a plug of celite, concentrated under reduced pressure and the residue was taken-up in ethyl acetate. The organic layer was washed with 1 M NaOH and saturated NaCI solution and finally was dried over Na2S04. Evaporation of the solvents under reduced pressure gave a clear oil. Yield: 1.44 g. 10 (ii) 1-Cyclopropyl-piperidin-4-ylamine N— To a solution of 0.72 g {1-Cyclopropyi-piperidin-4-yl}-carbamic acid tert-butyl ester in 5 ml DCM,3 ml TFA was added at RT. After stirring for 20 h the solution was diluted with 20 ml of toluene and evaporated under reduced pressure. The residue was codistilled twice with 15 toluene and was used in the subsequent reactions without further purification. The product was obtained as its trifluoroacetate salt. Yield: 870 mg. (iii) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indole-2-carboxylicacid (1-cyclopropyl-piperidin-4-yl}-amide 20 The title compound was prepared analogously to example 1 with the difference that 1-Cycloprppyl-piperidin^-ylamine was used instead of 1-lsopropyl-piperidin^-ylamine. MS (ESI+): m/e - 481, chloro pattern. Example 49:1-[5-(5-Ch!oro-thiopben-2-Yl}-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid [1-25 (tetrahydro-pyran-4-yl)-piperidin^-yI]-amide [i)4-({1-[5-(5-Chloro-thiophen-2--yl}-isoxazol-3-ylmethyl]-lH-indole-2-carbonyl)-amino}-piperidine-T-carboxylicacid tert-butyl ester o To a solution of 1 g 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1H-indole-2-carboxylic acid and 1.4 ml NEM in 5 ml DCM, 0.9 gTOTU were added and the mixture was stirred for 30 min at RT. Then 0.7 g4-Arnino-piperidine-1-carboxylic acid tert-butyl ester were added and the reaction was stirred for 16h. After removal of the solvent under reduced pressure the residue 10 was purified by chromatography on silica gel with ethyl acetate/heptane 4:1 as eluent The fractions containing the product were evaporated to give a white foam. Yield: 1 g. (ii) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid piperidin-4-ylamide O 15 CI To 1 g of 4-({l-[5-(5-Chloro-thiophen-2-yl)Hsoxa2ol-3-ylmethyl]-1H-indole-2-carbonyl}-amino)-piperidine-1-carboxyiicacid tert-buty! ester, 10 ml of methanolic hydrochloric acid (8M) were added and the mixture was stirred at RTfor2 h. After removal of the solvent under reduced 56 441 n fY-^>^0^: o -o /^ N 57 — O 0 r^ N 441 58 427 59 / N' N- o f Vci CI 439, chloro pattern 60 438 ^/\ H N )-N 61 'O o 405 62 441 63 413 64 0 Wj rv-^ \ , N^V^M / N 420 Example 65:1-(3-Methoxy-benzyl)-lH-indoie2-carboxylicacid (4-pyridin-4-yl-phenyl)-amide (i) 1-(3-MethoxY-benzyi}-lH-indole-2-carboxylic acid {4-iodo-phenYl)-amide N-0-' H O 0 To a solution of 50O mg 1-(3-Metfioxy-benzyl)-1 H-indole-2-carboxylic acid in 8 ml DCM and 0.9 ml NEt3 452 mg, BOP-Cl was added at RT and the mixture was stirred for 30 min. After addition of 583 mg 4-lodo-pheny!amine the mixture was stirred for 16h. Then the solvent was removed under reduced pressure to yield a white precipitate, which was washed with 1 ml MeOH/DCM 1:1. Yield: 380 mg. 5 (ii) 1-(3-Methoxv-benzYl)-lH-indole-2-carboxylic acid {4-pyridin-4-yl-phenyl)-amide A solution of 100 mg 1-{3-Methoxy-benzyl}-1H-indole-2-carboxylic acid (4-iodo-phenyl)-amide, 31 mg 4-Pyridyl boronic acid and 200 pi aqueous NajCO? solution {2M) in 5 ml dimethoxyethane (dme) was purged with argon for 15 min. Then 20 mg Pd(PPh3)4 was added and the mixture was heated to 80°Cfor 16h. Finally, 3 ml saturated NaHCOs solution were 10 added and the mixture was filtered through a chem elut® cartridge by elution with ethyl acetate. After subsequent removal of the solvent under reduced pressure the residue was purified by preparative HPLC (C18 reverse phase column, elution with a HzO/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophiiized to yield a white solid. The product was obtained as its trifluoroacetate salt. Yield: 15 mg 15 MS(ESI+):m/e = 434. Example 66: 4-Methoxy-1-{3-methoxy-benzyl)-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)- amide 20 The title compound was prepared analogously to example 52 with the difference that 4- Methoxy-1H-indole-2-carboxylicacid was used instead of lH-lndole-2-carboxylic acid. MS(ESI+):m/e = 436. 25 Example 67: 5-Chloro-1-(3-methoxy-benzyl)-1H-indo!e-2-carboxylic acid (1-isopropyl-piperidin- 4-yl)-amide Cl-.^/^^ ^ N-( N N O V O / The title compound was prepared analogously to example 57 with the difference that 5-Chloro-1H-indole2-carboxylic acid was used instead of IH-indole-2-carboxylicacid. MS (ESI+): m/e = 440, chloro pattern. 5 Example 68: 5-Methoxy-1-(3-methoxy-benzyl)-1 H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide 'O 10 The title compound was prepared analogously to example 52 with the difference that 6-Methoxy-1H-indo!e-2-carboxylicacid was used instead of 1H-indole-2-carboxylicacid. MS (ESH-): m/e = 436. 15 Example 69:1-(3-Methoxy-benzyf}-5-methyl-1 H-indole-2-carboxylic acid (l-isopropyl-piperidin- 4-yl}-amide ^ NK N N O O The title compound was prepared analogously to example 52 with the difference that 5-Methyl-lH-indole-2-carboxylicacid was used instead of 1H-indole-2-carboxylicacid. MS (ES1+}: m/e = 420. Example 70: 5-Benzyloxy-1-(3-methoxy-ben2yl)-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4- yl)-amide The title compound was prepared analogously to example 52 with the difference that 5-0 Benzyloxy-1H-indole-2 Example 71:1-(3-Methoxy-benzyl)-5-nitro-1,H-indole-2-carboxylicacid (1-isopropyl-piperidin^-i5 yl)- amide The title compound was prepared analogously to example 52 with the difference that 5-Nitro-1 H-indole-2-carboxylic acid was used instead of 1 H-indole-2-carboxylic acid. MS[ESI+):m/e = 451. Example 72: 5-Methoxy-1-(3-methoxy-benzyl}-lH-indole-2-carboxylicacid (1-isopropyi- piperidin-4-yl}- amide O^^^^ N- N o o The title compound was prepared analogously to example 52 with the difference that 5-5 Methoxy-1H-indole-2-carboxylic acid was used instead of 1H-indole-2-carboxylic acid. MS (ESI+): m/e = 436. Example 73: 1-(3-Methoxy-benzoyl)-1H-lndole-2-carboxYlicacid (1-isopropyl-piperidin- 10 4-yl)-amide ^ N^ N N O O / The title compound was prepared analogously to example 1 with the difference that 3- Methoxy-benzoyl chloride was used instead of 3-Bromomethyl-5-(5-chloro-thiophen-2-yl}- isoxazole. MS (ESI+): m/e = 420. 15 Example 74: 1-(3-MethoxY-benzenesulfonyl}-1H-indo!e-2-carboxylic acid (l-lsopropyl- piperidin-4-yl)- amide The title compound was prepared analogously to example 1 with the difference that 3- Methoxy-benzenesulfonyt chloride was used instrad of 3-Bromomethy!-5-(5-chforo-thiophen-2 ylHsoxazole. MS (ESf+): m/e = 456. 5 E)ample75: l-(4-Methoxy-phenyt)-1H-indole-2-carboxylicacid (T-isopropyl-piperidin- 4-yl}- amide 10 (i) 1-(4-Methoxy-phenYl}-1H'indoie-2-carboxyiicacid methyl ester To a suspension of 2 g lH-lndole-2-carboxyiic acid methyl ester, 3.2 g4-MethoxyphenYl boronicacid, 2 g molecular sieve (4A), 1.7 ml pyridine, 3 ml NEtj in 40 ml DCM, 3.9 g Cu{0Ac)2 were added. The suspension was stirred for 3 d at RT and for 2 d at 50°C then 3 ml saturated I N3HCO3 solution was added and the mixture filtered through a chem elut® cartridge by 15 elution with ethyl acetate. After concentration under reduced pressure and chromatographic purification on silica gel with ethyl acetate/ heptane 4:1 the fractions containing the product were evaporated. Yield: 3 g. (ii) 1-(4-Methoxy-phenyl}-1H-indole-2-carboxylicacid 20 To a solution of 3 g1-(4-Methoxy-phenyl)-1H-indo!e-2-carboxYlicacid methyl ester in 50 ml THF, 10 ml water and 0.58 g lithium hydroxidemonohydrate were added. After stirring for 2 h at 60°C the reaction was cooled to RT. The mixture was acidified with half concentrated hydrochloric acid and the precipitate was collected by filtration and was washed with 10 ml water The product was obtained as a white solid which was dried under reduced pressure. Yield; 520 mg. (vi) 1-(4'Methoxy-phenyl)-1H-indole-2-carboxylic acid (1-isopropyI-piperidin^-yl}- amide 5 To a solution of 36 mg 1-(4-Methoxy-phenyl)-1H-indole-2-carboxylic acid in 1 ml DCM and 0.17 ml NEt3 , 34 mg BOP-CI were added at RT and the mixture was stirred for 30 min. After addition of 57 mg 1-lsopropyi-piperidin-4-ylamine hydrochloride the mixture was stirred over night. Subsequently the solvent was removed under reduced pressure and the residue was purified by preparative HPLC (C18 reverse phase column, elution with a HiO/MeCN gradient 10 with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. The product was obtained as its trifluoroacetate salt. Yield: 14 mg MS (ES+): m/e = 329. 15 According to example 75 the following compounds were prepared by a similar procedure; Example Structure MS (ESI+) 76 o / 427 77 391 78 424 N 79 \/?o 405 -0 80 424 H 81 -o 441 \L .N CI 82 ,0 O 425, chloro pattern 83 413 84 427 85 427 Example 86: benzylamide 1-(4-Methoxy-phenyl)-1H-indole-2-carboxylic acid 4-pyridin-4-yl- (i) {4-Bromo-benzyl}-carbamic acid tert-butyl ester To a solution of 5 g 4-Bromo-benzyiamine and 7 ml NEt3 In 30 ml DCM 5.4 g B0C2O were added. After stirring for T6h at RT the reaction mixture was concentrated and the precipitate was collected by filtration. The solid product was dried under reduced pressure and was used 10 in the subsequent reaction without further purification. Yield: 6.5 g. (ii) [4-Pyridin-4-yl-ben2yl)-carbamic acid tert-butyl ester VN - - A solution of 500 mg (4-Bromo-ben2yl) 5 argon for 15 min. Then 60 mg Pd(PPh3)4 were added and the mixture was heated to 100°Cfor 16h. Finally, 10 ml saturated NaHCOj solution was added and the mixture was filtered through a chem elut® cartridge by elution with ethyl acetate. After subsequent removal of the solvent under reduced pressure the residue was purified by chromatography on silica gel with ethyl acetate as eluent. The fractions containing the produrt were evaporated to yield a white solid. 10 Yield: 490 mg. (iii) 4-Pyridin-4-yl-benzylamine HjN f= To a solution of 490mg(4-PyMdin^-yl-benzyl)-carbamicadd tert-butyl ester in 2 ml DCM, 3ml 15 TFA were added at RT. After stirring for 12 h the reaction mixture was diluted with 10 ml toluene and was evaporated under reduced pressure to yield a brown foam. The product was obtained as its trifluoro acetate salt. Yield: 330 mg (iv) 1-{4-Methoxy-phenyl)-lH-indole-2-carboxylic acid 4-pyridin-4-yl-ben2ylamide 20 To solution of 50 mg 1-{4-Methoxy-phenyl)-1H-indole-2-carboxylicacid and TOO pi NEts in 2 ml DCM, 47 mg BOP-CI were added at RT. After 1 h, 51 mg 4-Pyridln-4-yl-benzy!amine were added and the reaction mixture was stirred for 16h. After removal of the solvent under reduced pressure the residue was purified by preparative HPLC (CI 8 reverse phase column, elution with a HzO/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated 25 and were lyophilized to yield a white solid. The product was obtained as its trifluoroacetate salt Yield: 27 mg MS (ESH): m/e = 434. Example 87: 4-yI)- amide 1-(3-Methoxy-phenyl)-lH-indoie-2-carboxylicacid (l-isopropyl-piperldin- N -o H N^ O The title compound was prepared anaiogously to example 75 with the difference that 3-5 Methoxypheny! boronicacid was used instead of 4-Methoxyphenyl boronic acid. MS (ESI+): m/e = 392. Example 88: 10 yl)- amide T-(3-Chloro-phenyl)-1H-indole-2-carboxylicacid (l-isopropyI-piperidin-4- N CI H o 15 The title compound was prepared analogously to example 75 w'rth the difference that 3-Chlorophenyi boronic acid was used instead of 4-Methoxyphenyl boronic acid. MS (ESI+): m/e = 396, chloro pattern. Analogously to example 88 the following compounds were prepared by a similar procedure: Example Structure MS (ESH-) 89 CI 431, chloro pattern 90 a N O h 396, chloro pattern N O 91 409, chloro pattern o 92 417, chloro pattern N N O CI 93 431,chloro pattern "N N N. O 94 431,chloro pattern o 95 CI N J) NH, N 428, chloro pattern 96 445, chloro pattern 97 429, chloro pattern N—^ Example 98: 1-(3-Chloro-phenyl)-1 H-indo!e-2 6 5 The title compound was prepared analogously to example 86 with the difference that 1-(3-Chloro-phenyl)~1 H-indole-2-carboxy[ic acid was used instead of 1-(4-Methoxy-phenyl)-1 H-indole-2-carboxy!ic acid. MS (ES1+): m/e = 438, chloro pattern. 10 Example 99: l-(3,5-Dichioro-phenyl)-1 H-indole-2-carboxylic acid (1-isopropyi- piperidin-4-yI)- amide cr -^ -a The title compound was prepared analc^ously to example 75 with the difference that 3,5-Dichlorophenyl boronic acid was used instead of 4-Methoxy phenyl boronic acid. MS (ES1+): m/e = 430, chloro pattern. Analogously to example 99 the following compounds were prepared by a similar procedure: Example Structure MS (ESI+) noo 430, chloro pattern 101 465, chloro pattern 102 479, chloro pattern 103 465, chloro pattern 104 451,chloro pattern CI 105 CI N' CI. CI o 465, chloro pattern Example 106: 1-(4-Oiloro-phenyl)-1H-indole-2-carboxylicacid (l-iSQpropyl-piperidln-4-yl)-aniide ■^ N-^N^ C) N 0 The title compound was prepared analogously to example 75 with the difference that 4-Chlorophenyl boronic acid was used instead of 4-MethoxYphenyl boronic acid. MS (ESi+): m/e = 396, chloro pattern. Analogously to example 107 the following compounds were prepared by a similar procedure: Example Structure MS (ESI+) 108 428,chloro pattern 109 415,chloro pattern no 429, chloro pattern Ill 410, chloro pattern 112 445, chloro pattern H w 113 N O CI 431,chloro pattern W /.^ 114 431,chloro pattern 115 431, chloro pattern 116 N -i CI N O 396, chloro pattern Example 117: 1-(4-Chloro-phenyl)-1H-indole-2-carboxylicacid4-pyndin-4-yl-benzylamide 0 5 Thetitle compound was prepared analogously to example 86 with the difference that 1-(4-Chloro-phenyl)-1 H-lndole-2 N CrH N ^^N^ "A NH, The title compound was prepared analogously to example 1 with the difference that 7-Bromomethyl-quinazolin-4-ylamine [prepared by adopting a procedure desaibed by Ewing, William R.; Becker, Michael R.; Choi-Sledeski, Yong Mi; Pauls, Heinz W.; He, Wei; Condon, 5 Stephen M.; Davis, Roderick S.; Hanney, Barbara A.; Spada, Alfred P.; Burns, Christopher J.; Jiang, John Z.; Li, Aiwen; Myers, Michael R.; Lau, Wan F.; Poli, Gregory B. PQ Int, Appl. (2001), 460 pp. WO 0107436 A2] was used instead of 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole. MS (ESI+): m/e - 443. 10 Example 119: 1-(6-Chloro-benzo[b]thiophen-2-ylmethyl)-1H-indole-2 _ s 15 The title compound was prepared analogously to example 1 with the difference that 2-Bromomethyi-6-chloro-benzo[b]thiophene [prepared by adopting a procedure described by Ewing, William R. et al. in ;Pa Int. Appi. (1999), 300 pp. WO 9937304 Al; and Ewing, William R. et al, PCT int. Appl. (2001), 460 pp. WO 0107436 A2] was used instead of 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazQle. 20 MS[ES1+): m/e = 466, chloro pattern. Example: 120: 1-[5-(5-Chloro-thiophen-2-yl}-[1,3,4]thiadiazol-2-ylmethyl]-1H-indole-2- carboxylic acid (1-isopropyl-piperidin^yl)-amide N— ^ N O ^JL CI The title compound was prepared analogously to example 1 with the difference that 2-5 Bromomethyl-5-(5-chloro-thiophen-2-yl}-[1,3.4]thiadia2ole [prepared by adopting a procedure described by Ewing, William R. etal. PQlnt. Appl. (2001), 460 pp. WO 0107436 A2] was used instead of 3-Bromcmethyl-5-[5-chloro-thiophen-2-y!)-isoxazo!e. MS(ESI+): m/e = 500, chloro pattern. 10 Example: 121: 1-[3-(5-Chloro-thiophen-2-yl)-isoxa2ol-5-ylmethyl]-1H-indole-2-carboxylic acid (1- isopropyl-piperidin-4-yl)-amide CI The title compound was prepared analogously to example 1 with the difference that 5-15 Bromomethyl-3-(5 Example 122: 3-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yi)-amide To a soiution of 40 nng1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-1H-indole-2-carboxyiic acid {1- isopropyl-piperidin-4-y!}-amide in 1 ml DCM, 17 mg NCS were added and the mixture was stirred at RT for 16h. Finally, the reaction mixture was directly purified by preparative RP- 5 HPLC eluting with a gradient of 0-100% acetonitrile in water {-f- 0.01% trifluoroacetic acid). After lyophilization the product was obtained asitstrifluoroacetatesalt. Yield: 15 mg MS (ES-^): m/e = 517, chioro pattern. 10 Example 123: 3-Bromo-1-[5-(5-chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid {1-isopropyl-piperidln-4-y!)-amide Br To a solution of 40 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]TlH-indoie-2-carboxylic acid (1- isopropy!-piperidin-4-yl}-amide in 1 m! DQA, 22 mg NBS were added and the mixture 15 was stirred at RT over night. Finally, the reaction mixture was directly purified by preparative RP-HPLG eluting with a ^adient of 0-100 % acetonitrile in water 1+ 0.01% trifluoroacetic acid). After lyophilization the product was obtained as its trifluoroacetate salt. Yield: 18 mg MS (ES*)': m/e = 562, chioro pattern. 20 Example 124: 1-{4-Chloro-benzyi)-1H-indple-2-carboxylicacid (1-isopropyl-piperidin^-y!)-amide The title compound was prepared analogously to example 1 with the difference that 1-Chloromethyl-4-chloro-benzene was used instead of 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole. 5 MS (ESH-):m/e = 410, chloro pattern. Analogously to example 124 the following compounds were prepared by a similar procedure: Example Structure MS (ES1+) 125 445, chloro pattern 126 409, chloro pattern 127 CI N' o 423, chioro pattern 128 431, chioro pattern 129 443, chioro pattern 130 CI N^ N N ^ /, N 445, chioro pattern O =J > N 131 CI N^ H^N 442, chloro pattern ^A\ //^ 132 CI N O 445, chloro pattern 133 445, chloro pattern O 134 C! N 459,chloro pattern Example 135:1-(2,4-Dichloro-benzyl)-1H-indole-2-carboxYlicacid (1-isopropyl-piperidin-4-yI)-amide A N N O i> ■a CI The title compound was prepared analogously to example 1 with the difference that 1-Chloromethyl-2,4-dich!oro-ben2ene was used instead of 3-BromomethyI-5-(5-chloro-thiophen-2-yl)-isoxa2ole. 5 MS (ESI+): m/e = 444, chloro pattern. According to example 135 the following compounds were prepared by a similar procedure: Example Structure MS (ESI+) 136 465, chloro pattern 0 137 CI N"" 493,chloro pattern 138 479, chloro pattern 139 457, chloro pattern 140 479, chloro pattern 141 479, chloro pattern 142 476, chloro pattern 143 a 478, chloro pattern Example 144: 1-(4-Met1ioxy-benzyI)-1 H-mdole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide N H N O 5 "^o The title compound was prepared analogously to example 1 with the difference that 1- Chloromethy!-4-methoxy-benzene was used instead of 3-Bromomethyl-5-{5-chIoro-thiophen-2- yl)-isoxazole. MS (ESI+): m/e = 406. 10 Example 145: (4-lsopropylamino-piperidin-1-yl)-[1-(4-methoxy-benzyi)-1H-indol-2-yl]-methanone The title compound was prepared analogously to example 144 with the difference that 4-15 l50propy!-piperidin-1-yl-amine was used instead of 1-lsopropyl-piperidin^-ylamine. MS (ESH-): m/e = 406. Example 146: 1-[4-Trjfluoromethoxy-benzyl}-1H-indole-2-carbQxylic acid (1-isopropyl-piperidin-20 4-yl}- amide The title compound was prepared analogously to example 1 with the difference that 1- Bromomethyl-4-trifluoromethoxy-benzene was used instead of 3-Bromomethyl-5-{5-chloro- thiophen-2-yI)-i50xazole. MS (ESI+): m/e = 459. 5 Example 147: {4-lsopropylamino-piperidin-1-yl}-[1-{4-trifluoromethoxy-benzyl]-1 H- indol-2-yl]- methanone N O F 10 The title compound was prepared analogously to example 146 with the difference that Isopropyl-piperidin^-yl-amine was used instead of l-lsopropyl-piperidin-4-ylainine. MS(ESI+):m/e = 459. 15 Example 148: 1-(2-Chloro-benzyl)-1H-indole-2-carboxylic acid (1-Isopropyl-piperidin-4-yi)-amide CCVH!^"^ The title compound was prepared analogously to example 1 with the difference that 1- Bromomethyl-2-chloro-benzene was used instead of 3-Bromomethyl-5-(5-chloro-thlophen-2- yl)-isaxazole. MS (ESI+): m/e = 410, chloro pattern. According to example 148 the following compounds were prepared by a similar procedure; Example Structure MS (ESI+) 149 (X:J 410, chioro pattern 150 459, chloro pattern 151 409,chloro pattern 152 443, chloro pattern 153 431,chloro pattern 154 H CI n o 423,chloro pattern 155 445,chloro pattern ^ -^ 156 N' O N 445,chioro pattern Example 157; 1-(3,5-Dichloro-benzyl)-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl}- amide The title compound was prepared analogously to oample 1 with the difference that V Chloromethyl-3,5-dichloro-benzene was used instead of 3-Bromomethyi-5-{5-chloro-thiophen- 2-yl}-isoxazole. MS (ESI+): m/e = 444, chloro pattern. Example 158: methanone [1-(3,5-Dichloro-benzyl)-1H-indol-2-yl]-{4-isopropylamino-piperidin-1-yl)- 10 The title compound was prepared analogously to example 157 with the difference that Isopropyl-piperidin-4-yl-amlne was used instead of l-lsopropyl-piperidin-^-ylamine. MS (ESI+): m/e = 443, chloro pattern. 15 Example 159: 3-Fluoro-1-[5-(5-chioro-thiophen-2-yl)-isoxazol-3-yimethyl]-1H-indoie-2-carboxyticacid (1-isopropyl-piperidin^-yl)-amide F "\ H^"K To a solution of 40 mg 1-[5-(5-Chloro-thiophen-2-yI)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid (1- isopropyl-piperidin-4-yl)-amide in 1 ml DCM 22 mg N-Fluoropyridinium triflate were added and the mixture was stirred at RT for 4 days. Finally, the reaction mixture was directly purified by preparative RP-HPLC elutlng with a gradient of 0-100% acetonitrile in water 5 (+0.01% trifluoroacetic acid). After lyophilization the product was obtained as its trifluoroacetate salt. Yield: 22 mg MS (ES+): m/e = 501, chloro pattern. 10 Example 160: 1-[5-(5-ChiQro-thiophen-2-yl)-isoxazol-3-ylmethyi]-3-cyano-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-yl)-amide {i)3-iodo-1H-indole-2-carboxylicacid methyl ester 15 To a solution of 2 g 1 H-Indole-2-carboxylic acid methyl ester and 2.1 g KOH in 20 ml DMF a solution of 2.7 g Iz in 10 ml DMF were added dropwiseat RT. After 30 min the reaction mixture was diluted with a solution of 2.5 g NaHSOs in 100 ml water. The product was collected as a white precipitate by filtration and was washed with 10 ml water. Yield: 3 g. 20 (ii) 3-Cyano-1 H-indote-2-carboxylic acid methyl ester To a solution of 2 g3-lodo-1H-indole-2-carboxylicacid methyl ester in 10 ml DMF and 20 ml THF, 1.5gCuCN,434 mgEUNCN and 461 mg DPPF were added and the mixture was purged with argon for 15 min. Then, 254 mg Pd2(dba)3 were introduced and the reaction was heated to 80°Cfor 5h. Finally, 10 ml saturated NaHCOs solution were added and the mixture was 25 filtered through a chem elut® cartridge by elution with DCM. After subsequent removal of the solvent under reduced pressure the residue was purified by chromatography on silica gel with ethyiacetate as eluent. The fractions containing the product were evaporated to yield a white solid. Yield; 1.2 g. (iii)1-[5-{5-QilorQ-thiophen-2-yi}-isoxazol-3-ylmethyl]-3 (iv) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyI]-3-cyano-1 H-indole-2-carboxylic add This compound was prepared using a procedure analogous to that described for the 10 preparation of Example 1 (v), using 1-[5-(5-Chloro-thiophen-2-yI)-isoxazol-3-yimethyl]-3-cyano- 1 H-indole-2-carboxylic acid methyl ester as the starting material. (v) l-[5-{5-Chloro-th!ophen-2-yl}-isoxazol-3-y!methyl]-3-cyano-lH-indole-2-carboxylicacid (1- isopropyl-piperldin4-yI)-amide This compound was prepared using a procedure analogous to that described for the 15 preparation of Example 1 (vi), using 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-cyano- TH-indole-2-carboxylic acid as the starting material. MS (ES-*-): m/e = 508, chloro pattern. 20 Example 161; 1-[5-{5-Chloro-thiophen-2-yl)-lsoxazol-3-ylmethyl]-3-cyano-7-methyl-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide The title compound was prepared analogously to example 186 with the difference that 7- Methyi-1 H-indo!e-2-carboxylic acid methyl ester was used instead of 1 H-lndole-2-carboxylic 25 acid methyl ester. MS {ESI+): m/e = 522, chloro pattern. Example 162: 1-[2-(5-Chloro-thiophen-2-yl)-thiazol-5-ylmethyl]-1H-lndole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide The title compound was prepared analogously to example 1 with the difference that 5-5 Bromomethyl-2-{5-chIoro-thiophen-2-yl)-thiazole [prepared by adopting a procedure described by Ewing, William R. et al.; PCT Int. Appl. (2001), 460 pp. WO 0107436 A2] was used instead of 3-Bromomethyl-5-{5-chloro-thiophen-2-yl)-isoxazole. MS (ESi+): m/e = 499, chloro pattern. 10 Example 163: 1-(3-Chloro-benzyl)-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)- amide The title compound was prepared analogously to example 1 with the difference that 1- 15 Bromomethyl-3-chloro-benzene was used instead of 3-BromomethYl-5-(5-chloro-thiophen-2- yl)-lsoxazole. MS {ESI+): m/e = 410, chloro pattern. Example 164: [1-(3-Ch!oro-benzyl)-1H-indol-2-yl]-(4-isoprDpylamino-piperidin-1-yl)- 20 methanone The title compound was prepared analogously to example 163 with the difference that lsopropyl-piperidin-4-yl-aminewas used instead of 1-Isopropyi-piperidin-4-ylamine. MS (ESI+j: m/e = 409, chloro pattern. Example 165: 1-(3-Carbamoyl-benzyl)-1H-indole-2 10 The title compound was prepared analogously to example 1 with the difference that 3- Bromomethyl-benzamide was used instead of 3-Bromomethyl-5-(5-chloro-thiophen-2-yl) isoxazole. MS (ESI+): m/e = 419. 15 Example 166; 3-[2-(4-lsopropylamino-piperidine-1-carbonyl)-indol-1-ylmethyl]-benzaml( The title compound was prepared analogously to example 165 with the difference that Isopropyl-piperidin-4-yl-amine was used instead of 1-lsopropyl-piperidin-4-ylamine. MS(ESI+):m/e = 419. Example 167: l-iB^-Dimethoxy-benzylj-IH-indoIe-Z-arboxylicacid (1-isopropyl-piperidin^ yi)- amide The title compound was prepared analogously to example 1 with the difference that 1- ChloromethyI-3,5-dimethoxy-benzenewas used instead of 3-Bromomethyl-5-(5-chloro- thiophen-2-yl)-isQxa2ole. MS (ESI+): m/e = 435. } Example 168: [1-(3,5-Dimethoxy-benzyt)-lH-indol-2-yI]-(4-isopropylamino-piperidin-1-yl}- methanone- The title compound was prepared analogously to example 167 with the difference that tsopropyl-piperidin-4-y!-aminewas used instead of 1-lsopropyl-piperidin-4-ylamine. 5 MS(ESl+):m/e = 435. Example 169: 1-[2-{4-Chloro-phenyl)-ethyl]-1H-indole-2-carboxylic acid (1-isopropyl-piperidin- 4-yl)-amide. O (i)Toluene-4-sulfonic acid 2-(4-chloro-phenyl)-ethyl ester 5g(31.9mmol} of 2-(4-Ch!oro-phenyl)-ethanol was dissolved in 100 ml of pyridine and the solution was cooled to O^C 6.09g(31.9mmol)of para-toluene suifonyi chloride was added to this solution and the reaction was stirred at 0 °C for 2 h, then at room tennperaturefor16h. The solvent was removed under reduced pressure, the residue was taken-up in ethyl acetate 5 and the solution was washed once with saturated aqueous sodium bicarbonate, once with water, and once with saturated aqueous sodium chloride. The organic phase was dried with sodium sulfate, filtered and the solvent vras removed under reduced pressure. The compound was recrystallised from n-heptane/ethyl acetate. Yield; 623 g MS (a+): m/e = 311, chioro pattern. 10 (ii) 1-[2-{4-Chloro-phenyl}-ethyl]-1H-indole-2-carboxylicadd ethyl ester 0.5g{2.6mmDl)of lH-lndole-2-carboxylicacid ethyl ester was dissolved in DMFand 116 mg (2.9 mmol} of sodium hydride (60% dispersion in mineral oil) was added. The solution was stirred for 30 min at room temperature, then cooled to-78 °C A solution of 0.82 g (2.6 mmol) 15 of toluene-4-sulfonic acid 2-(4-chloro-phenyl)-ethyl ester in DMF was added to this cooled solution. The solution was warmed to RT and was stirred for 16 h. The solvent was removed under reduced pressure, the residue was taken-up in ethyl acetate and the solution was washed once with saturated aqueous sodium bicarbonate, once with water, and once with saturated aqueous sodium chloride. The organic phase was dried with magnesium sulfate, 20 filtered and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel elutingwith a gradient of n-heptane/ethyl acetate. Yield: 480 mg MS (CI+): m/e = 328, chioro pattern. (iii) 1-[2-(4-Chloro-phenyl)-ethyl]"1H-indole-2-carboxylic acid 25 480 mg (I.Bmmol) of 1-[2-(4-Chloro-phenyl}-ethyl]-1 H-indoIe-2-carboxylic acid ethyl ester was dissolved in 5 ml of dioxan and 5 ml of 2N aqueous sodium hydroxide was added. The reaction was heated to 60 °C for 2 h, then was cooled to 0 "C. The solution was diluted with 10 ml of water and the pH of the solution was adjusted to between 2 and 3 by the addition of concentrated aqueous HCl, whereupon the product precipitates. The product was filtered off 30 and dried under reduced pressure. Yield: 390 mg MS (a+): m/e = 300, chloro pattern. (jv) 1-[2-(4-Chloro-phenyl)-ethyl]-1H-indole-2-carboxylIcacid (1-isopropyl-piperidin-4-yl)-amide. 50mg (0.2mmoi) of 1-[2-[4-Chloro-phenyl)-ethy!]-1 H-indo!e-2-carboxy!Jc acid was dissolved in 2 ml of DMF and 54.7 mg (0.2 mmoi) of TOTU and 0.21 ml (1.7 mmol) of NEM was added. This solution was stirred at room temperature for 30 min. 35.9 mg (0.2 mmol) of 1-isopropyl-piperidin-4-ylamine dihydrochloride was added and the resulting solution was stirred at room 5 temperature for 16 h. The product was purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water(+0.01% trifluoroacetic add). After lyophilization the product was obtained as its trifluoroacetate salt. Yield: 46.9 mgMS fTOF-ES+): m/e = 424, chloro pattern, 10 Example 170: 1-[2-(2,4-Dichloro-phenyl}-ethyl]-1H-indole-2-carboxylic acid (l-isopropyl-piperidin-4-yi)-amide o CI {i}Toluene-4-sulfonicacid 2-(2,4-dichloro-phenyl)-ethyl ester 15 This compound was prepared using a procedure analogous to that described for the preparation of Example 169 (i), using 2-(2,4-dichloro-phenyl)-ethanol as the starting material. The compound was recrystallised from n-heptane/ethyl acetate. Yield: 7.12 g MS (0+]: m/e ^ 345, chloro pattern. 20 (ii) 1-[2-(2,4-Dichlorophenyl}-ethyl]-1H-indole-2-carboxylic acid ethyl ester This compound was prepared using a procedure analogous to that described for the preparation of Example 169 (ii), and using toluene-4-sulfonic acid 2-(2,4-dichloro-phenyl}-ethyl ester as the starting material. Yield: 91 mg MS (LC-MS-ES+): m/e = 362, chloro pattern. 25 (ili) l-[2-(2,4-DichlQrophenyl)-ethyl]-1H-indole-2-carbQxylicacid This compound was prepared using a procedure analogous to that described for the preparation of Example 169 (iii), using 1-[2-(2,4-Dichlorophenyl)-ethyl]-1H-indole-2-carboxylic acid ethyl ester as the starting material. Yield: 69 mg MS (0+): m/e = 334, chloro pattern. (iv) 1-[2-(2,4-Dichlorophenyl)-etfiyl]-1 H-indole-2-carboxyIic acid (1-isopropyl-piperidin-4-yl)-amide This compound was prepared using a procedure analogous to that described for the 5 preparation of Example 169 (iv), using 1 -[2-{2,4-Dichlorophenyl)-ethyl]-1 H-indole-2-carboxy!ic acid as the starting material. Yield: 69 mg MS {O*]: m/e ~ 334, chloro pattern. Example 171: 1-[2-{3-Methoxy-phenyi)-ethyl]-1H-indole-2 (I) Toluene-4-sulfonic acid 2-(3-methoxyphenyl)-ethyl ester This compound was prepared using a procedure analogous to that described for the preparation of Example 169 (i), using 2-(3-methoxYphenyl)-ethanol as the starting material. The 15 compound was chromatographed on silica gel eluting with n-heptane/ethyl acetate (4/1). Yield: 5.13 g. MS [0^): m/e = 306 (M^). (ii) l-[2-[3-Methoxy-phenyl)-ethyl]-1 H-indole-2-carboxylic acid ethyl ester This compound was prepared using a procedure analogous to that described for the 20 preparation of Example 169 (ii), using toluene-4-5Ulfonic acid 2-(3-methoxyphenyl)-ethyl ester as the starting material. Yield: 554 mg. MS (LC-MS-ES+): m/e = 324 (M+H+). (iii) 1-[2-(3-Methoxy-phenyl)-ethyl]-1 H-indole-2-carboxylic acid This compound was prepared using a procedure analogous to that described for the 25 preparation of Example 169 (Iii), using 1-[2-(3-Methoxy-phenyl)-ethyl]-1 H-indole-2-carboxylic acid ethyl ester as the starting material. Yield: 384 mg. MS (C1+): m/e = 296 (M+H+). (iv) 1-[2-(3-Methoxy-phenyl}-ethyl]-1 H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide This compound was prepared using a procedure analogous to that described for the preparation of Example 169 (iv), using 1-[2-(3-Methoxy'phenyI)-ethyl]-1H-indoIe-2-carboxylic 5 acid as the starting material. Yield: 44 mg MS (LC-MS-ES*): m/e = 419 (M+). Example 172: 1-[2-(4-Chloro-phenyl)-ethyi]-4-methoxy-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide 10 ^" This compound was prepared using a procedure analogous to that described for the preparation of Example 169, using 4-methoxy-1H-indole-2-carboxylic acid methyl ester as the starting material. Yield: 67 mg. MS (ES+): m/e = 454 (M+}, chloro pattern. 15 Example 173: 4-Bromo-1-[5-(5-chloro-thiophen-2-Yl}-isoxazol-3-ylmethyll-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yi)-amide Br The title compound was prepared analogously to example 1 with the difference that 4-Bromo-20 1H-indole-2-carboxylic acid was used instead of 1H-lndole-2-carboxylic acid. MS (ES}+): m/e = 562, chloro pattern. ExarBpte174: 1-[5-(5-Chloro-thiophen-2-yl)-!so)azol-3-Ylmethyll-4-methyl-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide 5 The title compound was prepared analogously to example 1 with the dffference that 4-Methyl-1H-indoIe-2-carboxyl(cacid was used instead of 1H-lndole-2-carboxylic acid. MS (ESI+): m/e = 497, chloro pattern. 0 Ejample 175: 5-Bromo-1-[5-(5-chloro-thiophen-2-y!)-tsoxazol-3-yimethy!]-lH-indote-2-carboxylic acid (l-isopropyl-piperidin-4-yl)-amide The title compound was prepared analogously to example 1 with the difference that S-Bromo-1H-indoIe-2-carboxylic add was used instead of IH-lndole-2-carboxyllc acid. I MS (ESI+): m/e = 582, chloro pattern. Example 176: 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-5-cyano-1H-indole-2-carboxylic acid (l-isopropyl-plperidin-4^-yl}-amicle The title compound was prepared analogously to example 1 with the difference that 5-Cyano- lH-indole-2-carbDxylic acid was used instead of IH-lndole-2-arboxylic acid. MS (ESt+}: m/e = 508, chioro pattern. 5 Example 177: 1-[5-(5-ChlorO'thiophen-2-yl)-isoxazol-3-ylmethyI]-4-trifluoromethyl-1H- indole-2- carboxylic acid (1-isopropyl-piperldin-4-yl)-amide The title compound was prepared analogously to example 1 with the difference that 4-TrifluoromethyI-1H-indole-2- carboxylicacid was used instead of 1H-lndole-2-carboxylic acid. 10 MS (ESI+); m/e = 551, chioro pattern. Example 178: 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4,7-dimethyl-lH- indole-2-carbpxylic acid (lMsopropyl-piperidin-4-yi)-amide 15 CI The title compound was prepared analogously to example 1 with the difference that 4,7-Dimethyl-1H-indole-2-carboxylic acid was used instead of 1H-lndole-2-carboxylic acid. MS {ESI+): m/e - 511, chioro pattern. Example; 179; 1-[5-[5-ChIoro-thiDphen-2-yI)-isoxazoI-3-y)methy)]-4,7-dimethoxy-1H- indole-2-carfaoxyiic acid (1-lsopropyl-piperidin-4-yl)-amide O-N I ci- 5 The title compound was prepared analogously to example 1 with the difference that 4,7- Dimethoxy-1 H-indoie-2-carboxylic acid was used instead of 1 H-lndoie-2-carboxylic acid. MS (ESI+): m/e = 543, chioro pattern. 10 Example: 180: 4,7-Dichloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-1 H-indole- 2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide CI The title compound was prepared analogously to example 1 with the difference that 4,7-15 Dichioro-1H-indole-2-carboxylic acid was used instead of 1H-lndole-2-carboxylic acid. MS (ESU-): m/e = 551, chioro pattern. Example 181: 5,7-Dichloro-1-[5-{5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-20 carboxylic acid (1-isopropyl-piperidin-4-yl)-amide The title compound was prepared analogously to example 1 with the difference that 5,7-Dichloro-1H-lndole-2-carboxylicacid was used instead of 1H-lndole-2-carboxy!ic acid. MS (ESIH-): m/e = 551, chloro pattern. Example 182: 4-Chloro-1-[5-[5-chlorQ-thiophen-2-yl}-isoxa2ot-3-ylmethyl]-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-yl}-amide CI H / N- 10 The title compound was prepared analogously to example 1 with the difference that 4-ChloroA-1H-indole-2-carboxy!icacid was used instead of 1H-lndole-2-carboxylicacid. MS (ESI+): m/e = 517, chloro pattern. 15 Example 183: l-[5-(5-Chloro-thiophen-2-yl)-isoxa2oi-3-ylmethyl]-1H-indole-2-carboxylicacld (4-methyl-piperazln-1-yl)-amide N-N N- The title compound was prepared analogously to example 1 with the difference that 4-Methyl-piperazin-1- was used instead of 1-IsopropYl-piperidin-4-ylamine. MS (ESI+); m/e =456, chloro pattern. 5 Example 184: [{l-[5-(5-Ch!oro-thiophen-2-ylKisoxazol-3-¥lmethyl]-7-methyl-1H-indole- 2-carbonylHl- isopropyl-piperidin-4-yl)-amino]-acetic add ethyl ester (i) [1-lsoprQpyl-piperidin-4-ylamino)-acetic acid ethyl ester 10 To a solution of 1 g 1-lsopropyl-piperidin 4-ylamine hydrochloride in 10 ml DMF, 1.2 g 2-Bromoacetic add ethyl ester, 23 g CszCOa, and 2 ml NEta, were added and the reaction mixture was stirred for2h at RT. Finally, 10 ml saturated NaHCOa solution were added and the mixture was filtered through a cartridge by elution with DCM. After evaporation of the solvent under reduced pressure the product was obtained as a white foam and employed in 15 the following reaction without further purification. Yield: 1.3 g. (ii) :[{1-[5-(5-Chloro-thiophen-2-yI}-isoxazol-3-ylmethyl]-7-methyl-1H-indble-2-carbQnylHl-i5opropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester 20 To a solution of 70 mg1-[5-{5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyI]-7-methyl-1H-indole-2-carboxylicacid in 1 ml DMF, 0.1 ml NEt?, 47 mg BOP-Ci and 81 mg (1-lsopropyl-piperidin4-ylamino)-aceticacid ethyl ester were added and the mixture was stirred for16h. After removal of the solvent under reduced pressure the residue was filtered through a chem elut® cartridge by elution with ethyl acetate and then purified by preparative HPLC (C18 reverse phase 25 column, elution with a HzO/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. The product was obtained as its trifluoroacetate salt. Yield: 9.3 mg MS (ES*): m/e= 583, chloro pattern. 5 Example 185: [{1-[5-(5-Chloro-thiophen-2-yi)-isoxazo!-3-ylmethyl]-7-methyl-1H-indole-2-carbonyl}-(1 - isopropyl-piperidin-4-yl}-annino]-acetic add To a solution of 15 mg [{1-[5-[5-Ch!oro-thioplien-2-yl)-isoxazol-3-ylniethyl]-7-methyl-1H-indoIe-2-carbonyl}-(1- isopropyl-piperidin-4-yl)-amino]-aceticacid ethyl ester in 2 ml water/THF 1:2, 10 25 pi aqueous NaOH solution (2M) were added and the reaction stirred for ;i6h at RT. The reaction mixture was acidified by addition of hydrochloric acid (5M), concentrated under reduced pressure and the residue taken-up in DCM. The inorganic salts were filtered off, the filtrate was concentrated under reduced pressure, taken-up in 1 ml water and lyophilized to yield a white solid. The product was obtained as its HCl salt. Yield: 5 mg MS [ES+): m/e= 555, 15 chloro pattern. Example 186: 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1H-indole-2-carboxylIcacid (1-(1- ethYl-prapyl)-piperidin-4-yl]-amide The title compound was prepared analogously to example 49 with the difference that Pentan- 3-one was used instead of Tetrahydro-pyran-4'One. MS [ESI+): m/e = 5T1, chloro pattern. 5 Example 187: 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-arboxylicacid (1-nriethyl-piperidin-4-yl)-amide To a solution of 50 mg 1-[5-{5-Chloro-thiophen-2-yI)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic .0 acid piperidin-4-ylamide in 1 ml DMF and 40 pi NEt3,24 mg methyl iodide were added at RT and the reaction mixture stirred for 4 h. After removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLC eluting with a gradient of 0-100 % acetonitrile in water (+ 0.01% trifluoroacetic acid). After lyophilization the product was obtained as its trifluoroacetate salt. .5 Yield: 32 mg MS (ES+): m/e ~ 455, chloro pattern. Example 188: 1-[5-(5-Chloro-th!ophen-2-yl)-isoxazol-3-ylmethyl]-lH-indole-2-carboxylicacid [1-(2,2,2-trif!uoro-ethyi)-piperidin-4-yl]-amide The title compound was prepared analogously to example 187 with the difference that 2-\odo1,1,T-tr5fiuoroethane was used instead ol methyl iodide. MS (ESI+): m/e = 523, chloro pattern. Example 189: 1-[5-(5-Ch!oro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1H-indole-2-carboxylic acid (1- formyl-piperidin-ii-yl}-amide To a solution of 50 mg 1-[5-(5-Chloro-thiophen-2-yi}-isoxazol-3-ylmethyl]-l H-indole-2-carboxylic acid piperidin'4-ylamide in 2 mi aretic acid, 14 mg KOCN were added at RT and stirred over niglit. After removal of the solvent under reduced pressure the residue directly purified by preparative RP-HPLC eluting with a gradient of 0-100 % acetonitrile in water (+ 6.01% 20 trifluoroacetic acid). After lyophilization the product was obtained as a white solid. Yield: 31 mg MS (ES^): m/e =- 484, chloro pattern. Example 191: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-y(methyl]-1H-indole-2-carboxylicacid (1-methanesulfonyl-piperidin-4-yl)-amide CI To a solution of 50 mg 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-tndole-2-carboxylic 5 acid piperidin-4-ylamide in 2 ml DCM, 0.3 ml NEts and 20 mg Methanesulfonyl chloride were added at RT and stirredfor16h. After removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLC eluting with a gradient of 0-100 % acetonitrile in water (+ D.01%trifluoroaceticacid). After lyophilization the product was obtained as a white solid. 10 Yield: 23 mg MS (ES^^): m/e = 519, chloro pattern. Example 192: 1-[5-(5-Chtoro-thlophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid {1-acetyl-piperidin-4-yl}-amide 15 To a solution of 50 mg 1-[5-{5-Chloro-thiophen-2-yi}-isoxazoi-3-ylmethyl]-1 H-indole-2-carboxyiic acid piperidin^-ylamide in 2 ml DCM, 0.3 ml NEtsand 11 mg acetic acid anhydride were added at RT and stirred over night. After removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLC eluting with a gradient of 0-100 % 20 acetonitrJie in water (+ 0.01%trifluoroacetic acid). After lyophilization the product was obtained as a white solid. Yield; 24 mg MS (ES+): m/e = 483, chloro pattern. Example 193: 1-[5-(5-Chloro-thiophen-2-yl}-isoxa2ol-3-ylmethyl]-1H-indole-2-carboxylicacid [1-(2- chloro-pyrimidin^^-yI)-piperidin-4-y!]-amide (i) [1-(2-Chloro-pyrimidin-4-yl)-piperidin-4-yl]-carbaniic acid tert-butyl ester To a solution of 500 mg Piperidin-4-yl-carbamic acid tert-butyl ester in 6 ml n-BuOH/water/NEt31:1:1, 557 mg2,4-Dichloro-pyrimidine were added and the reaction mixture was heated to 100°C over night. After cooling the reaction to RT, the solvent was evaporated 10 under reduced pressure and the residue was taken-up in ethyl acetate washed twice with water and then with brine. The organic layer was dried over Na2S04 and the solvent removed under reduced pressure. The residue was purified by chromatography on silica gel eluting with ethyl acetate/heptane 2:1. The fractions containing the product were evaporated under reduced pressure to give a white solid. 15 Yield: 630 mg. (ii) 1-(2-Chloro-pyrimidin-4-yl)-piperidin-4-ylamine To a solution of 250 mg [1-(2-Chloro-pyrimidin-4-yl)-piperidin-4-y!]-carbamic acid tert-butyl ester in 1 ml DCM, 1 ml TFAwas added and the mixture was stirred for 2 h at RT. Then, 10 ml 20 toluene was added and the solvents were removed under reduced pressure. The residue was codistilled twice with toluene to yield a yellow oil. The product was obtained as its trifluoroacetate salt. Yield: 367 mg. - ^ 25 (ii) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxyiic acid [1-(2- chloro-pyrimidin-4-yl)-piperidin-4-yl]-amide To a solution of 100 mg 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-y!methyl]-1 H-indoie-2- carboxylic acid in 3 ml of DCM 91 mg TOTU and 0.13 ml NEM were added. This solution was stirred at room temperature for 30 min. Then 148 mg 1-(2-Ch!oro-pyrimidin4-Yl)-piperidin-4- ylamine trifluoro acetate was added and the resulting solution was stirred at room 5 temperature for 16 h. The product was purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile In water(+0.01% trrfluoroacetic acid). After lyophilizatlon the product was obtained as its trifiuoroacetate salt Yield: 71 mg MS (ES+): m/e = 553, chloro pattern. .0 ^ Example 194: 1-[5-(5-Chloro-thiophen-2-yl)-jsoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid {1-pyrimidin-4-yt-p!peridin-4-yl)-amide N-^ 15 [i) (1-Pyrimidin-4-yl-piperidin-4-yl)-carbamicacid tert-butyl ester To a solution of 395 mg [1-(2-Chloro-pyrimidin-4-yl)-piperidin-4-yl]-carbamic acid tert-butyl esterin10mlethanoiand0.3mlaceticacid, 20 mgPd/C (10%) were added and the mixture purged with argon for 10 min. Then the flask was stirred under a hydrogen atmosphere for 5 h at RT. After addition of 10 ml ethyl acetate the reaction mixture was filtered through a pad of 20 celite. The solvent was evaporated under reduced pressure and the residue codistilled twice with toluene to give the product as a white solid. Yield: 468 mg. (ii) 1-Pyrimidin-4-yl-piperidin-4-ylamine To a solution of 468 mg(1-Pyrimidin-4-yl-piperidin-4-yl)-carbamic acid tert-butyl ester in 2 ml 25 DCM, 2 ml TFA were added and the mixture was stirred for 2 h at RT. Then, 10 ml toluene was added and the solvents were removed under reduced pressure. The residue was codistilled twice with toluene to yield a yellow oil. The product was obtained as its trifiuoroacetate salt. Yield: 703 mg. (iii) 1-[5-{5-<:hloro-thiophen-2-y to a solution of mg carboxylicacid in miof dcm mgtotu and ml nem were added. this was stirred at room temperature for min. then trifluoroacetate added the resulting h. product purified by preparative rp-hplc eluting with gradient acetonitrile water trifluoroacetic acid after lyophilization obtained as its salt.> Yield: 52 mg MS (ES*): m/e = 519, chloro pattern. Example 195: {1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indol-2-yl}-[4-(pyridin-t-15 yloxy)- piperidin-1-yl]-methanone I cr-Q, The title compound was prepared analogously to example 1 with the difference that 4- (Piperidin-4-yloxy}-pyridine [prepared by adopting a procedure described Baxter, Andrew Douglas; Owen, David Alan; Montana, John Gary; Watson, Robert John PQ Int. Appl. (1999), 44 20 pp. WO 9924399 A1] was used instead of VlsopropyI-piperidin-4-yIamine. MS(ESI+):m/e = 519, chloro pattern. Example 196: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indole-2-carboxylic acid [4-25 (1H-imidazol-4-yl}-phenyl]-amide The title compound was prepared analogously to example "1 with the difference that 4-(1 H-lmidazol-4-yI)-phenylamine was used instead of 1-lsopropyi-piperidin-4-ylamine. MS (ESI+): m/e = 500, chloro pattern. 5 Example 197: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-1H-indole-2-carboxylic acid (4-pyridin-3-yl-thiazol-2-yl)-amide The title compound was prepared analogously to example 1 with the difference that 4-Pyridin-0 3-yl-thiazol-2-ylamine was used instead of 1-lsopropyl-piperidln-4-ylamine. MS (ESIH-): m/e = 518, chloro pattern. Example 198: 1-[5-{5-Chloro-thiophen-2-yl)-lsoxazol-3-yimethyl]-1H-indole-2-carboxyjic acid [3-5 (pyrrolidine-l-carbonyl)-4,5-dihydro-isoxa2ol-5-yimethyl]-amide N- ;o The title compound was prepared analogously to example 1 with the difference that (5- Aminomethyl-4,5-dihydro-isQXazol-3-vl)-pyrrolidin-1-yl-methanonewas used instead of 1- lsopropyl-piperidin-4-ylamine. MS (ESI+): m/e = 538, chloro pattern. Example 199: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1-isobutyl-piperidin-4-yi)-amide The title compound was prepared analogously to example 187 with the difference that 1-lodo- 2-methylpropane was used instead of methyl iodide. MS (ESi+): m/e - 497, chloro pattern. 5 Example 200: 1-[5-{5-Ch)oro-thiophen-2-yl}-isoxa2ol-3-ylmethyl]-1H-indole2-carboxylic acid (1-propyl-piperidin-1^-y!)-amide N—( N- Ccv^ Cl The title compound was prepared analogously to example 187 with the difference that 1-10 lodopropane was used instead of methyl iodide. MS (ESI+): m/e = 483, chloro pattern. Example 201: 4-({1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1H-indoie-2- carbonyl}-amino)- piperidlne-l-carboxylicacid methyl ester f0~ 15 ' °-'^ To a solution of 50 mg 1-[5-(5-Chloro-thiophen-2-yI)-isoxa2ol-3-ylmethy!]-1 H-indole-2-carboxy!ic acid piperidin-4-ylamide in 2 ml DCM, 0.3 ml NEt3 and 20 mg Methyl chloroformate were added at RTand stirred over night. After removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLC eluting with a gradient of 0-100 % 20 acetonitrile in water {+ 0.01% trifluoroacetic acid). After lyophilization the product was obtained as its trifluoroacetate salt a white solid. Yield: 24 mg MS (ES-*-): m/e = 499, chloro pattern. 5 Example 202: 1-[5-{5-Chloro-thiDphen-2-yl)-isoxazol-3-ylmethyI]-1H-indole-2-carboxylicacid (4-isopropyt-piperazin-]-yl)-amlde (i) 4-Amino-pipera2ine-1-carboxylic acid tert-butyl ester To a solution of Piperazin-1-ylamine in 20 ml THE and 1.37 ml NEta, 22. g B0C2O in 5 ml THE 10 were added dropwiseatO°CThe reaction mixture was stirred for 16h at RT then 50 ml ethyl acetate and 20 ml water were added. The organic layer was separated, washed with brine and dried over Na2S04. After removal of the solvent under reduced pressure the product was obtained as a white solid. Yield: 1.53 g. 15 (ii) 4-({1-[5-(5-Giloro-thiophen-2-yl}-isoxazoi-3-ylmethyl]-1H-indole-2-carbonyl}-amino}- plperazinel-carboxylic acid tert-butyl ester To a solution of 1 g 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid and 1.3 ml NEM in 8 ml DCM, 9.14mgT0TU were added and the mixture was stirred for 30 20 min at RT. Then 673 mg4-Amino-piperazme-1-carboxylic acid tert-butyl ester were added and the reaction was stirred over night. After removal of the solvent under reduced pressure the residue was directly purified by chromatography on silica gel elutingwith an ethyl acetate/heptane gradient. Yield: l.lg. 25 (iv) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid piperazin-l-ylamide To 1.1g4-({1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}-amino)-piperazine-1-carboxylicacid tert-butyl ester in 5 ml MeOH, 20 ml sat methanolic HCl were added and the reaction was stirred for 5 h at RT. Then, 70 ml toluene were added and the solvents were evaporated under reduced pressure to yield a yellow solid. The product was obtained as its hydrochloride salt. Yield: 941 mg. (v) 1-[S-(5-ailoro-thiophen-2-yl)-isoxazol-3-y!methyf|-1H-indole-2-carboxvlic acid (4- 5 isopropyl-piperazin-1-yl)-amide To10Dmg1-[5-{5-Chlor(>-thtophen-2-yl}-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid piperazin-1-ylamide in 2 ml methanol and 2 ml DMF and 0.2 ml acetone, 0.42 ml of Na{CN)BH3 in THF(IM) were added and the mixture was heated to 80°C for 30 min. After cooling the reaction to RT the solvent was removed under reduced pressure and the residue was directly 10 purified by preparative RP-HPLCelutingwith a gradient of 0-100 %acetonitrile in water (+ 0.01% trifluoroacetic acid). After lyophilization the product was obtained as its trifluoroacetate salt. Yield: 39 mg MS {ESI+): m/e = 484, chloro pattern. 15 Example 203: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid (4-ethyl- piperazin-1-yl)-amide n O'N The title compound was prepared analogously to example 202 with the difference that 20 acetaldehyde was used Instead of acetone in the reductive amination step. MS [ESI+): m/e = 470, chloro pattern. Example 204: l-[5-{5-Chloro-thiophen-2-yl)-lsoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid 25 pyridin-4-yl-(3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide (i) Pyridin-4-yl-(3,4,5,6-tetrahydro-2H-[1,4']bipvridmyl-4-yl)-carbamic add tert-butyl ester A solution of 5 g Piperidin-4-yl-carbamic acid tert-butyl ester and 8 g 4-ChIoropyridine hydrochloride in 9 ml n-butanol/water/NEtj 1:1:1 was heated at 100 °Cfor48 h. Then the 5 reaction mixture was cooled to RT, concentrated under reduced pressure and directly purified by chromatography on silica gel eluting with DCM. The fractions containing the product were evaporated under reduced pressure to yield a white foam. Yield: 7 g. (ii) Pyridin-4-yl-(3,4,5,6-tetrahydro-2H-[l,4']bipyridinyl-4-yl}-amine 10 To 2 g Pyridin-4-yl-{3,4,5,6-tetrahydrb-2H-[1,4']bipyridinyl-4-yl)-carbamic add tert-butyl ester in 10 ml MeOH, 30 ml sat. methanolic HCl was added and stirred for 5 h at RT. Then, 70 ml toluene were added and the solvents were evaporated under reduced pressure to give a yellow solid. The product was obtained as its hydrochloride salt. Yield: 1.6 g. 15 (iii) 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-yImethyl]-1H-indole-2-c2rboxylic acid pyridin-4-yi-(3,4,5,6-tetrahydro-2H-[l,4']bipyridiny!-4-yl}-amide To a solution of 200 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indole-2-carboxylicadd and 0.3 ml NEM in 2 ml DCM, 182 mgTOTU were added and the mixture was stirred for 30 min at RT. Then 170 mg Pyridin-4-yl-(3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yi}- 20 amine were added and the reaction was stirred for16h. After removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLC eluting with a gradient of 0-100 % acetonitriie in water {+ 0.01%trifluoroacetlc add). After lyophilization the product was obtained as its trttluoroacetate salt. Yield: 39 nig MS (ES1+): m/e = 595, chloro pattern. 25 ( Example 205: 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-5-nitro-1H-indole-2-carboxylic acid pyridin-4-yi-(3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide The title compound was prepared analogously to example 204 with the difference that 1-[5-(5-5 Chloro-thiophen-2-yl)-isoxazol-3-yimethyl]-5-nitro-1H-indole-2-carboxyiic add was used instead of 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ytmethyl]-1 H-indole-2-carboxylic acid. MS (ESI+): m/e = 642, chloro pattern. Example 206: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-cyano-1H-indole-2-0 carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yI)-amide The title compound was prepared analogously to example 160 with the difference that 3,4,5,6-Tetrahydro-2H-[1,4']bipyridinyl-4-ylam!ne was used instead of 1-lsopropyt-piperidin-4-yiamine. MS (ESI-i-): m/e = 543, chloro pattern. Example 207: 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-3,7-diiodo-4-niethoxy-1H-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yl)-amide (i) 3,7-Diiodo-4-methoxy-1H-indole-2-carboxy!ic acid methyl ester To a solution of 1 g 4-Methoxy-1H-indole-2-carboxylic acid methyl ester in 15 ml DCM, 5.4 g Bi5[pyridine)iodonium(l) tetrafluoroborate were added at RT and the reaction was stirred over night. Then, the reaction mixture was diluted with 20 ml DCM and washed with sat NazSzOs 5 solution and water. The organic layer was separated and dried over Na2S04 and the solvent removed under reduced pressure. The residue was used in the subsequent reaaion without further purification. Yield: 1.6 g. (ii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-3,7-diiodo-4-methoxy-1H-indole-2- 10 carboxylicacid To a solution of 200 mg 3,7-Diiodo-4-methoxy-1 H-indo!e-2-carboxylic acid methyl ester In 2 ml DMF 20 mg (60% in oil) sodium hydride were added at RT. After stirring for 30 min 121 mg 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoIe [prepared by adopting a procedure described by Ewing, William R.; Becl 20 under reduced pressure the residue was treated with 30 mg lithium hydroxide monohydrate in THF/water 2:1. After stirring for 2 h at 60°C the reaction was cooled to RT. The mixture was acidified with half concentrated hydrochloric acid to pH 2 and the precipitate collected by filtration and washed with 3 ml water The product was obtained as a white solid which was dried under reduced pressure. Yield: 200 mg. 25 (iv) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3,7-dliodo-4-methoxy-lH-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide To a solution of 100 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-3,7-diiodo-4-methoxy-1H-indole-2-carboxylicacid and 0.1 ml NEM in 2 ml DCM, 63 mgTOTU were added 30 and the mixture was stirred for 30 min at RT. Then 41 mg 1-lsopropyl-piperidin-4-yIamine hydrochloride were added and the reaction was stirred for 2 h. After removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLC eluting with a gradientof 0-100 %acetonitriIe in water (+ 0.01% trifluoroacetic acid). After lyophilization the product was obtained as its trifluoroacetate salt. Yield; 67 mg MS (ESI+): m/e ~ 765, chioro pattern. 5 Example 208: 1-[5-{5-Chloro-thiophen-2-yl)Hisoxazol-3'ylmethyl]-3,7-dicyano-4-methoxy-1 H-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yl)-amide To a solution of 20 mg 1-[5-(5-Chloro-thiophen-2-yl}-isoxa2ol-3-ylmethyl]-3,7-diiodo-4-methoxy-10 1H-indole-2-carboxylicacid(1-isopropyI-piperidin-4-yl)-amidein 1 ml DMFand 1 mITHF, 14 mg CuCN, 4 mg Et4NCN, 5 mg DPPFwere added and the mixture was purged with argon for 15 min. Then, 3 mg Pdz(dba}3 were introduced and the reaction was heated for 5 min to 120 °C under microwave irradiation (150 W, CEM Discover™ apparatus). Finally, 10 ml saturated NaHCOs solution were added and the mixture was filtered through a chem elut® cartridge by 15 elution with DCM. After removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLCeluting with a gradient of 0-100 %acetonitri!e in water (+ 0.01% trifluoroacetic acid). After lyophilization the product was obtained as its trifluoroacetate salt. Yield: 3 mg MS (E51+): m/e = 563, chioro pattern. 20 Example 209: 1-[2-(4-Chloro-phenyl)-thiazoU-ylmethyl]-1H-indale-2-carbpxyIicacid (I--isopropyl- piperidin-4-yl)-amide The title compound was prepared analogously to example 1 with the difference that 4- Chioromethyl-2-(4-chIoro-phenyl)-thiazole was used in the alkyiation step instead of 3- Bromomethyl-5-(5-chloro-thiophen-2-yl}-isoxa2ole. MS (ESI+): m/e = 493, chloro pattern. 5 Example 210: 1-(1,7-Dichloro-isoquinolin-3-ylmethyl)-1H-indole-2-carboxylic acid {1-isopropyi-piperidin-4-yl)'amide CI 10 The title compound was prepared analogously to example 1 with the difference that 3-Bromomethyl-1,7-dichloro-isDquinoline [prepared by adopting a procedure described by Ewing, William R.; Becker, Michael R.; Choi-Sledeski, Yong Mi; Pauls, Heinz W.; He, Wei; Condon, Stephen M.; Davis, Roderick S.; Hanney, Barbara A.; Spada, Alfred P.; Burns, ChristopherJ."; Jiang, John Z.; Li,Aiwen; Myers, Michael R.; Uu, Wan F.; Poll, Gregory B; PCT 15 Int. Appl. (1999), 300 pp. WO 9937304 Al] was used in the alkyiation step instead of 3- Bromomethyl-5-(5-chIoro-thiophen-2-yl)-isoxazole. MS (ESl+l; m/e = 495, chloro pattern. 20 Example 211: 1-[3-(4-Chloro-phenylHsoxazol-5-y!methyl]-1H-indole-2 The title compound was prepared analogously to example 1 with the difference that 5- Chloromethyl-3-{4-chloro-phenyl)-isoxazole was used in the alkylation step instead of 3- Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole. MS (ES1+): m/e = 477, chloro pattern. Example 212: l-[5-{4-Chloro-phenyl)-isoxazol-3-yimethyl]-1H-indole-2-carboxylic acid (1-isopropyl- piperidin-4-yl)-amide 10 The title compound was prepared analogously to example 1 with the difference that 3- Chloromethyl-5-(4-chloro-phenyl}-isoxazole was used in the alkylation step instead of 3- BromomethYl-5-(5-chlor(>-thiophen-2-y!)-isoxa2ole. MS (ESI+): m/e = 477, chlovo pattern. 15 Example213: l-[3-(4-Chloro-phenyl)-[l,2,4]oxadiazol-5-ylmethyl]-1H-lndoie-2-carboxyllcacJd (1- isopropyl-piperidin-4-yl)-amide The title compound was prepared analogously to example 1 with the difference that 5- 20 Chloromethyl-3-{4-chloro-phenyl)-[l,2,4]oxadia2ole was used in the alkylation step instead of 3- Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxa2o[e. MS (ESI+): m/e = 478, chloro pattern. Example 214: 1-[{5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-methanesulfonyl-lH-indoie-2-carboxylic acid (1-isopropy!-piperidin-4-yl)-amide CI (i) 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide 5 To a solution of 5g 5-Chloro-pyridin-2-ylamineand 1.5 ml pyridine in 30 ml toluene, 8 g bromo-acetyl bromide dissolved in 10 ml toluene was added dropwise under ice cooling. After 2 h the precipitate was isolated by filtration and recrystallized from toluene to yield a white solid. Yield: 12 g. 10 ■ (ii) 1-[{5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-methane5ulfonyl-1H-indoie-2-carboxylic acid To a solution of 1 g 5-Methanesulfonyl-1 H-indole-2-carboxylic acid methyl ester in 10 ml DMF, 158mg(60%in oil) sodium hydride were added at RT. After stirring for 10 min 985 mg2- 15 Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added and the mixture was stirred for 2 h. After the addition of 7 ml water the mixture was filtered through a chem elut® cartridge by elution with ethyl acetate and concentrated under reduced pressure. The residue was taken-u[ in 10 ml water/THF 1:2 and treated with 2 mi aqueous KOH solution (10%). After stirring for 16h at RT the reaction mixture was acidified with hydrochloric acid (5M). The precipitate was 20 collected by filtration and dried in vacuo to yield the product as a yellow solid. Yield: 1.1 g. (iii) 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-methanesulfonYl-lH-indole-2-carboxyllc acid (1-isopropyl-piperidin-4-yi)-amide To a solution of 500 mg 1-[(5-Chloro-pyridin-2-ylcarbamoyl}-methyi]-5-methanesulfonyl-1H-25 indole-2-carboxyiic acid in 5 ml DMF and 0.7 ml NEta, 312 mg BOP-Cl and 264 mg 1-lsopropy' piperidin-4-ylamine hydrochloride were added at RT and the mixture was stirred for 16h. Subsequently the solvent was removed under reduced pressure and the residue was purified by preparative HPLC (CIS reverse phase column, elution with a HiO/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and iyophilized togivea white solid. The product was obtained as its trifluoroacetate salt. 5 Yield: 364 mg MS fES+): m/e = 532, chloro pattern. Example 215; 1-[{4-Chloro-phenylcarbamoyl)-methyl]-5-methanesutfonyl-1H-indole-2-carboxylic acid (1- isopropyl-piperidin-^yl)-amide CI The title compound was prepared analogously to example 214 with the difference that 2-10 Bromo-N-(4-chloro-phenyl)-acetamIde was used instead of 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide in the alkylation step. MS {ESI+): m/e = 531, chloro pattern. 15 Example 216: 5-Chloro-1-[(5-chloro-pyridin-2-ylcarbamoyl)-methylj-1H-indole-2-carboxylic acid {1- isopropyl-piperidin-4-yl}-amide CI The title compound was prepared analogously to example 214 with the difference that 5- Chloro-1H-indole-2-carboxylicacid methyl ester was used instead of S-Methanesulfonyl-IH- 20 indole-2-carboxylic acid methyl ester. MS (ES1+): m/e = 488, chloro pattern. Example 217: 1-[(5-Chloro-pyridin-2-yIcarbamoy!)-methyr|-5-fIuoro-lH-indole-2- carboxylicacid (1- i50propyl-piperidin-4-yl)-amide F 5 The title compound was prepared analogously to example 214 with the difference that 5- Fluoro-1H-indole-2-carboxylicacid methyl ester was used instead of 5-Methanesulfonyl-1H- indole-2-carboxylic acid methyl ester. MS (ESI+): m/e = 472, chloro pattern. 10 Example 218: 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5,7-difIuoro-1 H-indole-2-carboxylic acid {1- isopropyl-piperidin-4-yl)-amide CI The title compound was prepared analogously to example 214 with the difference that 5,7- 15 Difluoro-1H-indo!e-2-carboxyllcacid methyl ester was used instead of-5-Methanesulfonyl-1H- indole-2-carboxylic acid methyl ester. MS (ESH-): m/e = 490, chloro pattern. Example 219: S-1-[5-(5-Chloro-thlophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid 20 (1-ethyl- pyrrolidin-3-yi)-amid S^\^^ N- i V— ■N O The title compound was prepared analogously to example 36 with the difference that 3S-3-tert.Butoxycarbonylpyrrolidine was used instead of (1-lsoprDpyl-piperidin-4-yl}-carbamic acid tert-butyl ester in the reductive amination step. MS CESI+): m/e = 455, chloro pattern. Example 220: R-1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyri-1H-indole-2 ■N o 10 The title compound was prepared analogously to example 36 with the difference that 3R-3-tert.ButoxycarbonylpyrroIidine was used instead of (1-Isopropyl-piperidin-4-yl)-carbamlc acid tert-butyl ester in the reductive amination step. MS (ESU-): m/e = 455, chloro pattern. .15 Example 221: R-1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethy!]-1H-indole-2-carboxylic acid (1- isopropyl-pyrrolidin-3-y!}-amide The title compound was prepared analogously to example 1 with the difference that 3R-3-tert.Butoxycarbonylpyrrolidine was used instead of (1-lsopropyl-piperidin-4-yl)-carbamic acid 20 tert-butyl ester in the reductive amination step. MS (ESI+): m/e = 469, chloro pattern. Example 222: S-1-[5-(5-ChIoro-thipphen-2-yl)-isoxazDi-3-ylmethyl]-1 H-indoie-2-carboxyiic acid {1-isopropy!-pyrroHdin-3-yl)-amide The titie compound was prepared analogously to example 1 with the difference that 3S-3-5 tert.Butoxycarbonylpyrrolidine was used instead of (1-lsopropyl-piperidin-4-yI)-carbamicacid tert-butyl ester in the reductive amination step. MS (ESI+): m/e = 469, chloro pattern. Example 223: [{1-[5-(5 The title compound was prepared analogously to example 184 with the difference that 1-[5-(5- Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-trlfiuoromethyi-1 H-indole-2- carboxylic acid was used instead of 1-[5-(5-ChlorQ-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1H-indole-2- 15 carboxylic acid. MS (ESI+): m/e = 637, chloro pattern. Example 224: [{1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]^,7-diniethyi-1H- indole-2-carbonyI}- {1-isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester The title compound was prepared analogously to example 184 with the difference that 1-[5-(5- Chloro-thiophen-2-yl}-i50xazol-3-ylmethyl]-4,7-dimethyI-1H-indole-2-carboxyiic acid was used instead of 1-[5-{5-Chloro-thiophen-2-yI)-isoxazol-3-yimethyI]-7-methyl-1H-indole-2-carboxylic 5 add. MS (ESI+): m/e =, 597, chloro pattern. 0 Example 225; [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4,7-dimethoxy-lH- indole-2- carbonylHT-isopropvl-piperidin-4-yl)-amino)-acetic acid ethyl ester J The title compound was prepared analogously to example 184 with the difference that 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-4,7-dimethoxy-1H-indole-2-carboxylic acid was used instead of 1-[5-(5-Chloro-thiophen-2-yi)-isoxazoi-3-ylmethyi]-7-methyl-1 H-indole-2-carboxylic acid. MS (ES1+): m/e = 629, chloro pattern. Example 226: [{4,7-Dichloro-1-[5-(5-chloro-thiophen-2-yI)-isoxazol-3-Ylmethyll-1H-indole-2- carbonyl]- (1-isopropyl-piperidin-4-Yl)-amino]-acetic acid ethyl ester The title compound was prepared analogously to example 184 with the difference that 4,7- Dichloro-1-[5-{5-ch!oro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid was used instead of 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1H-indole-2- 5 carboxylic acid. MS (ESH-): m/e = 638, chloro pattern. Example 227: [{5,7-Dichloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H- inciole-2-carbonyi}- (1-isopropyl-piperldin-4-yl)-amino]-acetic acid ethyl ester The title compound was prepared analogously to example 184 with the difference that 5,7- 10 Dichloro-l-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-!ndo!e-2-carboxylic acid was used instead of 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1 H-indole-2- carboxylic acid. MS (ESU-): m/e = 638, chloro pattern. 15 Example228: [{4-Chloro-l-[5-(5-chloro-thiQphen-2-yl}-isoxazol-3-ylmethyl]-1H-indale-2 carbonyl}-(1- isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester The title compound was prepared analogously to example 184 with the difference that 4-Chlor&-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indo!e-2-carboxytic acid was used instead of 1-[5-(5-Chloro-thiophen-2-yl)-lsoxazol-3-ylmethyl]-7-methyl-1H-indole-2-carboxylic 5 acid. MS (ESI+}: m/e = 603, chloro pattern. Example 229: [{1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-trifIuoromethyl-1H- 10 indole-2- carbonyl}-(1-isopropyI-piperidin-4-yl)-amino]-acetic acid o The title compound was prepared analogously to example 185 with the difference that [{1-[5- (5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-trifluoromethyl-1H-indole-2-carbonyl}-{'-isopropyl-piperidin-4-yl}-amino]-acetic acid ethyl ester was used instead,of [{1-[5-(5-Chloro- 15 thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1H-indole-2-carbonyl}-(1- isopropyl-plperidln-4-yl)-amlno]-acetic acid ethyl ester. MS {ESI+): m/e = 609, chloro pattern. Example 230: [{1-[5-{5-Chloro-thiophen-2-yl)-lsoxazol-3-ylmethyl]-4,7-dimethyi-1H- 20 indole-2-carbonyl}- [1-isopropyl-plperidin-4-yl)-amino]-acetic acid The title compound was prepared analogously to example 185 with the difference that [{1-[5- (5'Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-4,7-dimethyl-1H-indole-2-carbonyl)-{1-isopropyl- piperidin-4-yl)-amino]-acetic acid ethyl ester was used instead of [{1-[5-{5-ChiQrc>-thiophen-2- 5 yi}-isoxazol-3-ylmethyl]-7-methyl-1H-indole-2-carbonyl}-(l- isopropyl-piperidin-4-y!)-amino]- acetic acid ethyl ester. MS {ESH-): m/e = 569, chloro pattern. ( Example 231: [{1-[5-{5-ChIoro-thiophen-2-yi}-isoxa2ol-3-y!methyr|-4,7-diinethoxy-1H- 10 indole-2- carbonyi}-(1-isopropyl-piperidin-4-yl)-amino]-acetic acid o The title compound was prepared analogously to example 185 with the difference that [{l-[5-(5-ChIoro-thiophen-2-yl)-i50xazol-3-y!methyl]-4,7-dlmethoxy-1H-indole-2-carbonyl}-[1-isopropyl-plperidin-4-yl)-amino]-aceticacid ethyl ester was used instead of [{1-[5-(5-Chloro-15 thiophen-2-yi}-isoxazol-3-ylmethyl]-7-methyl-1H-indole-2-carbonyl}-(1- isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester. MS (ES1+): m/e = 601, chloro pattern. Example 232: [{4,7-DichIoro-l-[5'(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethYl]-1H- 20 indDle-2-carbonyl}- (1-isopropyl-piperidin-4-yl)-amino]-acetic acid The title compound was prepared analogously to example 185 with the difference that [{4,7- Dichloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}-(1-i5opropyl- piperidin-4-yl)-amino]-acetic acid ethyl ester was used instead of [{1-[5-(5-Chloro-thiophen-2- 5 yl}-isoxazol-3-ylmethyl]-7-methy!-1 H-indQle-2-carbonyl}-(1- isopropyl-piperidin-4-yl)-amino]- acetic acid ethyl ester. MS (ES1+): m/e = 609, chloro pattern. Example 233: [{5,7-Dichloro-l-[5-(5-chloro-thiophen-2-yI}-isoxazol-3-ylmethyl]-lH- 10 indole-2-carbonyl}- (1-isopropyi-piperidin-4-yl)-amino]-acetlc acid The title compound was prepared analogously to example 185 with the difference that [{5,7- Dichloro-1-[5-(5-chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}- (1-isopropyl- piperidin-4-yl)-amino]-acetic acid ethyl ester was used instead of [{'l-[5-(5-Chloro-thiophen-2- 15 yl)-isoxazol-3-ylmethyl]-7-methyl-lH-indole-2-carbonyl}-(1'i5opropyl-piperidin^-yl)-amino]- acetic acid ethyl ester. MS (ES1+}: m/e = 609, chloro pattern. ■ Example 234: [{4-Chloro-1-[5-{5-chIoro-thiophen-2*yi)-isoxazol-3-ylmethyl]-1H-indo!e-2- 20 carbonyl}-(1- isopropyl-piperidin-4-y!)-amino]-acetic acid The title compound was prepared analogously to example 185 with the difference that [{4- Qiloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}-(1- isopropyl- piperidin-4-yl}-amlno]-acetic add ethyl ester was used instead of [{1-[S-(5-Chloro-thiophen-2- 5 yl)-isoxazol-3-ylmethyl]-7-methyl-1H-indoie-2-carbonylHl-isopropyl-piperidin-4-yl)-amino]- acetic acid ethy! ester. MS (£S(+): m/e = 575, chloro pattern. Example 235: 1-[5-(5-Chloro-thiophen-2-yl)-i50xazo!-3-ylmethyl]-2-(l-isopropyl-piperidln-4- 10 ylcarbamoyl)-1H-indole-5-carboxylicacid isopropyl ester O N— (i) 1H-lndole-2,5-dicarboxyl;cacid 2-ethyl ester 5-isopropyi ester To a solution of 15.5g AlCb in 400 ml DCM, 10 ml oxalyl dichloride was added dropwise. Then, after 30 min 10 g 1H-lndoie-2-carboxylicacid ethyl ester in 100 ml DCM were added and the 15 reaction mixture was stirred for 2 h. The reaction mixture was poured on to crushed ice and extracted twice with 500 ml DCM. The organic layer was dried over MgS04 and the solvent removed under reduced pressure. The residue: was taken-up in 300 ml Propan-^-ol and stirred for 4 h at room temperature. After concentration of the reaction mixture under reduced pressure the residue was purified by chromatography on silica gel eluting with an ethyl 20 acetate/heptane gradient 1:10 -> 4:1. Yield: 2.71 g. (ii) 1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1H-indole-2,5-dicarboxylic acid 2- ethyl ester 5-isopropyl ester This compound was prepared using a procedure analogous to that described for the preparation of example 1 (rv), using 1 H-lndole-2,5-dicarboxylic acid 2-ethyl ester S-isopropyl 5 ester as the starting mato-ial. The compound was purified by chromatography on silica gel eluting with n-heptane/ethyl acetate 6:1. Yield 6.3 g. MS (ESI+}: m/e = 473 (M+) chloro pattern. (iii) l-[5-(5-Chloro-thiophen-2-yl}-isoxazoi-3-ylmethyl]-1 H-indole-2,5-dicarboxyiic acid 5- 10 isopropyl ester To a solution of 6.21 g 1-[5-(5-Chloro-thiophen-2-y!)-isoxa2ol-3-ylmethyl]-1 H-indole-2,5-dicarboxylic acid 2- ethyl ester 5-isopropyl ester in 100 ml THF and 40 ml MeOH 52 ml of an aqueous 1M LiOH solution were added and stirred for 2 h. The organic solvents were removed under reduced pressure and the residue acidified with 2 M hydrochloric acid to pH 2. The 15 precipitated product was collected by filtration and dried over P2O5 in vacuo to yield a white solid. Yield: 5.77 g. (iv) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-{1-i5opropyl-piperidin-4-ylcarbamoyl}-IH-indole-S-carboxylicacid isopropyl ester 20 To a solution of 5.77 g 1-[5-(5-Chloro-thiophen-2-Yl)-isoxazol-3-ylmethYl]-1H-indole-2,5- dicarboxylic acid 5- isopropyl ester and 2.79 g 1-lsopropyl-piperidin-4-ylamine hydrochloride in lOOmlDMF, 4.25gT0TUand6.6ml DIPEA were added and the mixture was stirred for 3 h at room temperature. After removal of the solvent under reduced pressure the residue was dissolved in 200 ml ethyl acetate and washed with sat. NaHCCh solution. The organic layer was 25 dried over MgS04. After removal of the solvent under reduced pressure the residue was purified by chromatography on silica gel eluting with DCM/MeOH/AcOH/HzO 95:5:0.5:0.5. The fractions containing the product were collected and the solvent evaporated under reduced. * pressure. The product was obtained as its acetate salt. Yield; 6.13 g MS (ES^): m/e =569, ■ chloro pattern. 30 Example 236: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-Ylmethyl]-2-(1-isopropyl-piperidln-4-ylcarbamoyl)-1 H-indole-5-carboxylic acid C! To a solution of 6.13 g 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyr|-2-{1-isopropyl- piperidin-4- ylcarbamoyl}-1H-indole-5-carboxylic acid isopropyl ester in 200 ml MeOH-54 ml of a 1M aqueous LiOH solution were added and heated for 24 h to 60 °C The reaction mixture 5 was the concentrated under reduced pressure and acidified with 2 M hydrochloric acid to pH 3. Then the mixture was extracted with ethyl acetate {2X200 ml) and the organic layer was dried over MgS04 which yielded after evaporation of the solvent under reduced pressure 5.3 g of the crude acid as a yellow solid. 600 mg of this acid were purified by preparative HPLC (CIS reverse phase column, eiution with a HzO/MeCN gradient with 0.1% TFA}. The fractions containing the 10 product were evaporated and lyophilized after addition of 2M hydrochloric acid to give a white solid. The product was obtained as its hydrochloride. Yield: 280 mg MS (ES+): m/e =527, chloro pattern. 15 Example 237: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yimethyl]-5-hydroxymethyl-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-yl)-amide O N— To a solution of 100 mg 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isoprQpyl-piperidin-4-ytcaFbamoyl)-1H-indole-5-carboxylicacid and 50 pi HEU in4mlTHF, 17 pi ethyl 20 chloroformate were added at -7°C. After stirring for 2 h at -7°C the reaction mixture was filtered, the filtrate was treated with 24 mg NaBH4 and warmed to room temperature. After 2 h additional 24 mg NaBH^ were added and the reaction mixture stirred for 16 h. Then, 110 pi MeOH in 4 ml THF were added within 2 h and the reaction mixture was stirred for additional 4 h at room temperature. After removal of the solvents under reduced pressure the residue was purified by chromatography on silica gel eiuting with DCM/MeOH 8:2. The fractions containing the product were collected and evaporated under reduced pressure. Yield: 39 mg MS (ES*); m/e =513, chloro pattern. Example 238: l-[5-(5-Chloro-thiophen-2-yl}-isoxazoi-3-ylmethyl]-2-{1-isopropyI-piperidin-4-ylcarbamoyl)-1H-indole5-carboxylicacid ethyl ester o N—( N- 10 To a solution of 0.6 g 1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-yimethyl]-2-(1-isopropyl- piperidin4- ylcarbamoyl)-! H-indole-5-carboxylic acid in 10 ml DMF sequentially 0.4 ml EtOH, 110 mgDMAPand 256 mg DCC were added and the reaction mixture was stirred for 16 h at room temperature. The precipitate was then filtered off and the filtrate was concentrated and purified by chromatography on silica gel eiuting with DCM/MeOH/AcOH/HzO 95:3:0.5:0.5. The 15 fractions containing the product were collected and the solvent evaporated under reduced pressure. Yield: 418 mg MS (ES+): m/e =555, chloro pattern. 20 Example 239:' 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-5-carboxyllcacid methyl ester o N—( N- The title compound was prepared analogously to example 238 with the difference that methanol was used instead of ethanol in the esterification reaction. MS {ESI+): m/e = 541, chloro pattern. 5 AlternativeJy the title compound can be prepared by the following procedure: (i) 1H-lndole-2,5-dicarboxylic acid 5-methyl ester A solution of 25 g 4-Amino-3-iodo-benzoic acid methyl ester, 19 ml 2-Oxo-propionic add, 30.4 g 1,4-Diaza-bicyclo[2.2.2]octane and 1 g Pd(0Ac)2 was heated under argon to lOO^C After 5 h the reaction mixture was concentrated under reduced pressure and the residue was 10 partrtioned between 300 ml ethyl acetate and 200 ml 1 M hydrochloric acid. The organic layer was dried over MgS04 and the solvent removed under reduced pressure to yield a yellow solid (6.4 g). From the aqueous layer additional product slowly precipitated as a white solid (7.9 g) which was collected by filtration. Both fractions were combined, dried in vacuo and used in the next reaction without further purification. Yield: 14.3 g MS(ES^); m/e =220. 15 ■ (li) 1 H-lndole-2,5-dicarboxylic acid 2-tert-butyl ester 5-methyl ester To13g1H-lndole-2,5-dicarboxylicacid 5-methyl ester in 300 ml toluene, 59 ml Di-tert-butoxymethyl-dimethyl-amine were added dropwise at 80°C Then, the reaction mixture was heated under reflux for additional 6 h. After removal of the solvents under reduced pressure 20 the residue was dissolved in 300 ml DCM and washed with sat. aqueous NaHCOasolution (2X100 ml). The organic layer was dried over MgS04 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluting with a n-heptane/ethyl acetate gradient. The fractions containing the produrt were collerted and concentrated under reduced pressure. 25 Yield: 8.3 g MS (ES^: m/e =276. (iii) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2,5-dicarboxy!icacid 2-tert-butyl ester 5-metby) ester This compound was prepared using a procedure analogous to that described for the 30 preparation of example l(iv), using 1H-lndo!e-2,5-dicarboxylic acid 2-tert-butyl ester 5-methyl ester as the starting material. The compound was chromatographed on silica gel eluting with n-heptane/ethyl acetate 6:1. Yield 9.5 g. MS (ESI-f); m/e = 417, chloro pattern. (iv) 1-[5-(5-Chioro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2,5-dicarboxy!icacid 5- methyl ester 9.5 g 1-[5-{5-ChIoro-thiophen-2-yl)-isoxazo!-3-yimethyi]-1 H-indole-2,5-dicarboxylic acid 2- tert-buty! ester 5-methyl ester were dissolved in 300 ml trifluoro-acetic acid and stirred for 1 h at 5 RT. Then 200 ml toluene were added and the solvents were removed under reduced pressure. This procedure was repeated three times, then the residue was dried in vacuo. Yield: 8.4 g. (v)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-{1-isopropyl-piperidin-*-ylcarbamoYl)-1H-indole-5-carboxylic acid methyl ester 10 This compound was prepared using a procedure analogous to that described for the preparation of example 1 (vi), using 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1 H- indole-2,5-dicarboxylic acid 5- methyl ester as the starting material. The compound was chromatographed on silica gel elutingwith DCM/MeOH/AcOH/HzO 95:3:0.5:0.5. Yield 10 g. MS (ESI+}: m/e = 541, chloro pattern. 15 Example 240: 1-[5-(5-Chlor{>-thiophen-2-Yl)-isoxazol-3-y!methyi]-2-(1-isopropyl-piperidin-4-yfcarfaamoyi}-lH-indole-5-carboxylic acid 2,2-dimethy(-propiony(oxYmethyi ester 0 d N"( N CI 20 To a solution of 1.2 g 1-[5-(5-Chloro-thiophen-2-Yl}-isoxazai-3-ylmethyl]-2-(1-isopropyl-piperidin-4- yicarbamoyI}-1H-indole-5-carboxyl(C acid in 30 ml DMF 0,641 g2,2-Dimethyl-propionic acid chloromethyl ester and 885 \i\ NEts were added and the reaction mixture was stirred for 5h at 60 °C. Then additional 0,32 g 2,2-Dimethyl-propionic acid chloromethyl ester and 295 MI NEts were added and the reaction mixture was stirred for 6h at 60 "C. After removal 25 of the solvent under reduced pressure the residue was dissolved in CHiCband the solution was washed with water. The phases were separated and the organic phase (after drying over Na2S04) was concentrated in vacuo. The residue was purified by preparative RP-HPLC eluting with a gradient of 0-100 % acetonitrile in water (+ 0.01% trifiuoroacetic acid). After addition of 1 M hydrochloric acid and lyophilization in an acetonitrile/water mixture, the product was obtained as its hydrochloride. . Yield: 1,17g MS (ESH-): m/e = 641, chloro pattern. 5 Example 241: 1-[5-(^Chloro-thJophen-2-yl}-[1,3,4}thiadiazol-2-ylmethyl]-2-(1-i5opropyl-piperidin-4- yIcarbamoyl)-1H-indole-5-carboxylic acid isopropyl ester O The title compound was prepared analogously to example 235 with the difference that 2-10 Bromomethyl-5-(5-chloro-thiophen-2-yl)-[1,3.4]thiadiazole [prepared by adopting a procedure described by Ewing, William R. et al. PCT Int. Appl. (2001), 460 pp. WO 0107436 A2] was used instead of 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole. MS(ESI+}: m/e - 586, chloro pattern. 15 Example 242: 1-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadJazol-2-yimethyl]-2-(1-isopropyl-piperidin-4- ylcarbampy!)-1 H-indole-5-carboxylic acid o The title compound was prepared analogously to example 236 with the difference that 1-[5-{5-20 Chloro-thiophen-2-yl)-[1,3,4]thiadiazcl-2-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H indole-B-carboxylic acid isopropyl ester was used instead of l-[5-{5-Chloro-thiophen-2-yl}-!soxazol-3-ylmethyl]-2-(l-isopropyt-plperidin-4-ylcarbamoyl)-1H-indole-5-carboxy!icacid isopropyl ester. MS(ESI+): m/e = 544, chloro pattern. Example 243: 1-K4-Chloro-phenylcarbamoyl)-methyl]-2-(1-isopropyl-plperidin-4-ylcarbamoyl)-5 IH-indole- 5-carboxylic acid isopropyl ester O N—( N CI (i) 1H-lndole-2,5-dicarboxylic acid 5-isopropyl ester To a solution of 855 mglH-lndole-2,5-dicarboxylic acid 2-ethyl ester 5-isopropyl ester in 50 ml MeOH, 12.4 ml 1 M aqueous LiOH solution were added. After heating the reaction mixture at 10 50°C for 1 h the organic solvents were removed under reduced pressure and the residue was acidified to pH 2 with 1 M hydrochloric acid. The precipitated product was collected by filtration and dried in vacuo. Yield: 673 mg. (ii) 2-(1-lsopropyi-piperidin-4-ylcarbamoYl)-1H-indo!e-5-carboxyiicacid isopropyl ester 15 To a solution of 673 mg1H-lndole-2,5-dicarboxylic acid 5-isopropyl ester and 702 mgl-lsopropyl-piperidin4-ylamine hydrochloride in 20 ml DMF, 1.07gTOTU and 1.67 ml DiPEA were added and the mixture was stirred for 1 h at room temperature. After removal of the solvent under reduced pressure the residue was dissolved in 100 ml DCM and washed with sat. NaHCCh solution. The organic layer was dried over MgS04. After removal of the solvent under 20 reduced pressure the residue was purified by chromatography on silica gel eluting with DCM/MeOH/AcOH/HiO 95:5:0.5:0.5. The fractions containing the product were collected and the solvent evaporated under reduced pressure.The product was obtained as its acetate salt. Yield: 698 mg. 25 (iii) 2-Bromo-N-(4-chloro-phenyl)-acetamide To a solution of 5 g 4-Chloro-phenyiamine and 1.5 ml pyridine in 30 ml toluene, 8 gbromo-acetyl bromide dissolved in 10 ml toluene was added dropwise under ice cooling. After 2 h the precipitate was isolated by filtration and recrystallized from toluene to yield a white solid. Yield: 10 g. 5 Cfv}1-[(4-Qiloro-phenylcarbamoyl)-methyl]-2-{1-isopropyl-piperidin-4-ylcarbamoy!}-1H-indole-5-carboxylic add isopropyl ester To a solution of 100 mg2-{1-lsopropy(-piperidin-4-ylcarbamoyll-1H-mdole-5-carboxylicacid isopropyl ester In 2 ml DMF, 8 mg sodium hydride (60% in oil) were added at RT. After 30 min 10 67 mg 2-Bromo-N-(4-chloro-phenyl)-acetamide were added and the reaction mixture was stirred for 3 h. After removal of the solvent under reduced pressure the residue was purified by preparative RP-HPLC eluting with a gradient of 0-100 % acetonitrile in water (+ 0.01% trifluoroacetic acid). After lyophiiization the product was obtained as its trifSuoroacetate salt. Yield: 66 mg MS (ESI+); m/e = 539, chloro pattern. 15 Example 244: l-[{4-ChlorO'phenylcarbamoyl)-methyl]-2-{1-isDpropyl-piperidin-4-ylcarbamoyl)-IH-indole-5-carboxylic acid O N— CI 20 To a solution of 1.2 g 1-[(4-Ch!oro-phenylcarbamoyI)-methyI]-2-(1-isopropyi-plperidin-4-ylcarbamoyl)-1H-indole-5-carboxylic acid isopropylester in ISOmi MeOH.Il ml of a 1 M aqueous LiOH solution were added and the reaction mixture was heated to 60°C for 24 h. Then after concentration under reduced pressure the residue was acidified to pH2with 2M hydrochloric acid. The precipitated product was collected by filtration and purified by 25 chromatography on silica gel eluting with DCM/MeOH/AcOH/HjO 95:3:0.5:0.5. The fractions containing the product were collected and concentrated under reduced pressure. After addition of3m! 2 M hydrochloric acid and lyophilization the product was obtained as its hydrochloride. Yield: 499 mg MS (ESI+): m/e = 497, chloro pattern. 5 Example 245: 1-[5-(5-Chloro-thlophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isQpropyl-piperidin-*-ylcarbamoyi}-1H-indole-4-carboxylicacid methyl ester N—( N 10 0) 4-Bromo-1H-indole-2-carboxylic acid tert-butyl ester To7g4-Bromo-lH-indo[e'2-carboxylicacid in 150 ml toluene, 28 ml Di-tert-butoxymethyl-dimethyl-amine were added dropwise at 80°C. The reaction mixture was heated under reflux for additionari2h. After removal of the solvents under reduced pressure the residue was dissolved in 200 ml DCM and washed with sat. aqueous NaHCOasolution (2X50 ml). The organic 15 layer was dried over MgS04 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel elutingwith n-heptane/ethyl acetate 9:1. The fractions containing the product were collected and concentrated under reduced pressure. Yield: 6.5 g MS (ESI+): m/e = 297. 20 (ii) 1H-lndole-2,4-dicarboxylicacid2-tert-butyl ester 4-methyl ester To a solution of 7.3 g4-Bromo-1H-indole-2-carboxylic acid tert-butyl ester in 100 ml DMF, 6.8 ml NEt3,276mg Pd(0Ac)2,128 mg1,1'-Bis(d!phenylphosphino)ferrocene, 12 ml MeOH were added and purged with argon for 15 min. This solution was then purged with cafbon monoxide and heated to 70°C for 4 h. The reaction mixture was concentrated under reduced 25 pressure, the residue dissolved in 200 ml DCM and washed with 100 ml water. The organic layer was dried over MgS04 and, after removal of the solvent under reduced pressure, the residue was purified by chromatography on silica gel eluting with n-heplane/etbyl acetate 9:1. The fractions containing the product were collected and concentrated under reduced pressure. Yield: 3.8 g MS (ESI+): m/e = 276. 5 (iii) l-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-lH-indole-2,4-dicarboxy!ic acid 2-tert-butyl ester 4-methyl ester This compound was prepared using a procedure analogous to that described for the preparation of example 1 (iv), using 1 H-lndole-2,4-dtcarboxylic acid 2-tert-butyl ester 4-methyl ester as the starting material. The compound was chromatographed on silica gei eluting with 10 n-heptane/ethyl acetate 6:1. Yield 4.1 g. MS (ESU-}: m/e = 473(M+) chloro pattern. ^' (iv) 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1H-indole-2,4-dic3rboxylic acid 4- methyl ester 4.1 g1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2,4-dicarboxylicacid 2-tert- 15 butyl ester 4-methYl ester were dissolved in 100 ml trifluoro-acetic acid and stirred for 1 h at RT. Then 100 ml toluene was added and the solvents were removed under reduced pressure. This procedure was repeated three times, then the residue was dried in vacuo. Yield: 3.4 g MS (ESH-): m/e = 416, chloro pattern. 20 (v) 1-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-ylmethyl]-2-(Tisopropyl-piperidin-4' ylcarbamoyl)-1H-indoIe-4-carboxylic acid methyl ester This compound was prepared using a procedure analogous to that described for the preparation of example 235 (iv), using 1-[5-(5-Chloro-thiophen-2-yl)-i50xazol-3-ylmethyl]-1 H-indole-2,4-dicarboxylic acid 4- methyl ester as the starting material. The compound was 25 chromatographed on.silica gel eluting with DCM/MeOH/AcOH/HzO 95:3:0.5:0.5. Yield 4.2 g. MS {ESI+): m/e = 541, chloro pattern. Example 246; 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yimethyl]-2-(1-isopropyl-piperidin-4'-30 ylcarbamoyl)-1H-fndole-4-carboxylic acid 11 N' O 0-N This compound was prepared using a procedure analogous to that described for the preparation of example 236, using l-[5-(5-Chloro-thlophen-2-yl)-isoxazol-3-ylmethyl]-2-{1-isopropyl-piperidtn-4- ylcarbamoyl)-! H-indote-4-carboxylic acid methyl ester as the starting 5 material. The compound was chromatographed on silica gel eluting with DCM/MeOH/AcOH/HzO 95:3:0.5:0.5. MS (ESI+): m/e = 527 (M+), chloro pattern. Example 247: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2,5-dicarbDxylic acid 5- amide 2-[(l-isopropyI-piperidin-4-yl)-amide] N— o 10 The title compound was isolated as a by-product in example 176. MS (ES+): m/e= 526, chloro pattern. 15 Example 248: 1-[{4-chloro-phenylcarbamoyl)-methyl]-1H-indole-2-carboxylicacid (l-isopropyl-piperidin-4-yl)-amide N" N cr (i) 1H-lndole-2-carboxylicacld benzyl ester To a solution of 10.32 g IH-indoIe-2-carboxylic acid in 100 ml tetrahydro-furan 10.38 g di- imidazol-1-yl-methanone were added and the mixture was stirred for 20 min at room temperature. 7.29 ml phenyl-methanol were added to the mixture and the reaction mixture was refluxed for 10 h. The mixture was allowed to cool to ambient temperature and then 5 partitioned between 200 ml water and 200 ml dichloro-methane. The organic layer was washed with additional water and then dried over sodium sulphate. After filtration the solvent was removed under reduced pressure ,a white solid was obtained. The residue was directly subjected to the subsequent reaction without further purification. Yield: 18.8 g MS (ES*): m/e= 252, chloro pattern. 10 1H-NMR (400 MHz, DMSO/TMS): 5 =7.65 (d, 1H). 7.40 (m, 7H); 7.25 (t, 1H); 7.20 (s, IN); 7.07 (t. 1H);539(s,2H). (ii) 1-tert-Butoxycarbonylmethyl-1H-indoIe-2-carboxyiic acid benzyl ester To a solution of 18.80 g IH-indole-2-carboxylic acid benzyl ester in 70 ml N,N- 15 dimethylformamide 1.98 g sodium hydride were added at 0°C After stirring for 1 hour 15.91 ml bromo-acetic acid tert.-butyi ester were added to the mixture and the reaction mixture was stirred for 2 hours at room temperature. After removal of the solvent under reduced pressure the residue was partitioned between 300 ml water and 300 ml dichloromethane. The aqueous layer was washed twice with additional 200 ml dichloromethane. Subsequently the combined 20 organic phases were washed with a saturated aqueous solution of sodium chloride. After filtration the solvent was removed under reduced pressure and the residue was crystallized from ethoxy-ethane/heptane. The product was obtained as a white solid, rield: 23.8 g MS (ES+): m/e= 366, chloro pattern. 1H-NMR (400 MHz, DMSO/TMS): 5 =7.70 (d. 1H), 7.62 (d, IN); 7.46 {d, 2H); 7.38 (m, 5H); 7.15 (t, 25 1H); 5.35 (s, 2H); 5.28 (s, 2H); 1.39 (s, 9H). (iii) 1-tert.-ButoxycarbonylmethyI-1H-indole-2-carboxYiic acid To a solution of 3.0 g 1-tert.-butoxycarbonylmethyl-1 H-indoIe-2-carboxylic acid benzyl ester in a mixture of 10 ml N,N-dJmethylformamideand 10 ml ethanol 0.5 g palladium, 5% an carbon 30 were added. The reaction mixture was stirred for 2 hours under a hydrogen atmosphere. The mixture was filtered through a chem elut® cartridge and the compound was eluted with ethanol. After concentration under reduced pressure the residue was directly subjeaed to the subsequent reaction without further purification. Yield: 2.2 g. 1H-NMR (400 MHz, DMSO/TMS): 5 =12.50 (s, 1H); 7.68 (d, 1H), 7.59 (d. 1H); 7.31 (t, 1H); 725 (s. 5 1H); 7.13 (t, 1H); 5.26 (s, 2H); 1.40 {s, 9H) (iv) tert.-Butyl [2-{1-isopropyl-piperidin-4-yIcarfaamoyl)-indol-1-yl]-acetate To a solution of 0.5 g 1-tert.-butoxycarbonylmethyl-1H-indole-2-carfaoxylic acid and 0.91 ml N- ethylmorphoiine in 3 ml dichloromethane 0.6 g 0-[(ethoxycarbonyl) cyanomethylenamino]- 10 N,N,N',N'-tetramethyluronium tetrafluoroborate were added and the mixture was stirred for 30 min at room temperature. 0.39 g 1-isopropyl-piperidin-4-ylamine hydrochloride were added to the mixture and the reaction mixture was further stirred for 1 hour. After removal of the solvent under reduced pressure the residue was partitioned between 15 ml water and 15 ml dichloromethane. The organic layer was washed with additional water and then dried over 15 sodium sulphate. After filtration the solvent was removed under reduced pressure and a white solid was obtained. The residue was directly subjected to the subsequent reaction without further purification. Yield: 0.51 g MS(ES+): m/e= 400. 1H-NMR (400 MHz, DMSO/TMS): 5 =8.38 (d, 1H); 7.63 (d, 1H); 7.51 (d, IH); 7.25 (t, 1H); 7.20 (s, 20 1H); 7.11 (t, 1H); 5.27 {s, 2H); 3.55 (m, 1H); 2.82 (m, 2H); 2.30 (m, 1H), 2.18 (m, 2H); 1.77 (m, 2H); 1.55 (m, 2H); 1.39 (s, 9H); 0.98 (d, 6H). (v) [2-(1-lsopropyI-piperidin-4-ylcarbamoyl)-indol-Vyl]-aceticacid To 0.51 gtert.-butyi [2-(1-isopropyl-piperidln-4-ylcarbamoyl)-indol-1-yr|-aceticacid in 5 ml 25 dichloro-methane 1 ml trifluoroacetic acid was added and the mixture was stirred for 16 hours. Removal of the solvent under reduced pressure yielded a white solid, which was coevaporated twice with 15 ml toluene. The product was obtained asitstrifluoroacetatesalt. Yield: 0.43 g MS (ES+): m/e= 344. 1H-NMR (400 MHz, DMSOrfMS): 5 =12.6 (1H); 9.17 (s, 1H); 8.56 (d, 1H); 7.66 (d, 1H); 7.53 (d, 30 1H); 7.27 (t, 1H); 7.25 (s, 1H}; 7.11 (t, 1H); 5.30 (s, 2H}; 4.02 (m, 1H); 3.43 (m, 2H); 3.10 (m, 2H), 2.06 (m, 3H); 1.83 (m,2H); 1.25 (d, 6H). (vi) l-[(4-Chloro-phenyfcarbamoyl}-methyl]-l H-indole-2-carboxylic add (1-isopropyl- piperidin-4-yl)-amide To a suspension of 50 mg [2-{1-isopropyl-piperidin-4-ylcarbamoyI)-indo!-1-y[]-acetic acid, 22 mg 4-chloro-phenylamine and 37 mg bis(2-oxo-3-oxazolidinyl}phosphinic chloride in 1 ml 5 dichloro-methane 0.08 ml N-ethylmorpholine were added at room temperature and the mixture was stirred for 16 hours. After removal of the solvent under reduced pressure the residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% tnfluoroacetic acid). The fractions containing the product were evaporated and h'ophilized to yield a white solid. The product was obtained as its 10 trifluoroacetate salt. V Yield: 12.6 mg MS (ES"^): m/e= 453, chloro pattern. 1H-NMR (300 MHz, DMSO/TMS): 5 =10.44 (s, 1H); 8.95 (s, IH); 8.58 (d, 1H); 7.67 {d, 1H); 7.60 (d, 2H); 7.58 (d, IH); 7.35 (d, 2H); 7.28 (t, IH); 7.25 (s, IH); 7.13 (t, IH); 5.45 (s, 2H); 4.03 (s, IH); 3.43 (m, 2H); 3.08 (m, 2H), 2.05 (m, 3H); 1.80 (m, 2H); 1.23 (d, 6H), 15 Example 249: 1-[(5-chloro-thiophen-2-ylcarbamoyl)-methyl]-1H-indole-2-carboxylicacid (1-isopropyl- piperidin-4-yl)-amide N 0,-^ O k .N- li cr -^ 20 The title compound was prepared analogously to example 248 with the difference that 5- Chloro-thiophen-2-ylamine [prepared according to a procedure published in Synth. Comm, 1977, 255-256] was used instead of 4-chloro-phenyiamine. MS (ES1+): m/e = 459, chloro pattern. 1H-NMR(300 MHz, DMSO/TMS): 6 =11.72 (s, IH); 8.90 (s, IH); 8.57 (d, IH); 7.68 (d, IH); 7.58 (d, 25 IH); 7.27 (t, IH); 7.25 (s, IH); 7.14 (t, IH); 6.88 (d, IH); 6.53 (d, IH); 5.46 (s,2H); 4.00 (s, IH); 3.43 [m, 2H}; 3.08 (m, 2H), 2.03 (m, 3H); 1.80 (m, 2H); 1.23 (d, 6H) Example 250: 1-[(4-chloro-2-fluoro-phenyicarbamoyI)-methyl]-1H-!ndo!e-2-carboxy!icacid (1-isopropyl- piperidin-4-yl)-amide cr ^^ F The title compound was prepared analogously to example 248 with the difference that 4-5 Chloro-2-fluaro-phenylamine was used Instead of 4-chloro-phenyiamine. MS (ESI+): m/e = 471, chioro pattern. 1H-NMR (300 MHz, DMSOATMS): 5 =10.24 (s, 1H); 8.93 (s, 1H); 8.60 (d, 1H}; 7.95 (t, 1H}; 7.68 (d, 1H); 7.55 (d, 1H); 7.50 (d, 1H); 7.26 (d, 1H); 7.24 (s, 1H); 7.22 (s, 1H); 7.13 (t, 1H); 5.48 (s, 2H); 4.04 (s, 1H}; 3.43 [m, 2H}; 3.10 {m, 2H), 2.08 (m, 3H); 1.80 (m, 2H); 1.25 (d, 6H). 10 Example 251: 1-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indoIe-2-carboxylicacid (1-isopropyl- piperidin-4-yI)-amide N IS N Oi¬ls The title compound was prepared analogously to example 248 with the difference that 5- Chloro-pyridin-2-ylamine was used instead of 4-chloro-phenylamine. MS (ESI+): m/e = 454, chioro pattern. 1H-NMR (300 MHz, DMSO/TMS): 5 =10.99 (s, 1H); 8.90 (s, 1H); 8.58 (d, 1H); 8.39 (d, 1H); 7.97 (d,' 1H); 7.87 [dd. 1H); 7.68 (d, 1H); 7.56 (d, 1H); 7.27 (t, IH); 7.25 (s, 1H}; 7.13 (t, 1H); 5.45 (s,2H); 20 4.02 (s, IH); 3.43 (m, 2H); 3.08 (m, 2H). 2.03 (m, 3H); 1.80 (m, 2H); 1.23 (d, 6H). Example 252: 1-[{4-chloro-phenylcarbamoyl)-methyl]-1 H-indole-2-carboxylic acid (3,4,5,&-tetrahydro-2H-[1,4']bipyridinyl-4-ylmethyt}-amide a' (i) 1-[{4-Chtoro-phenylGarbamoyl)-methyl]-1H-indole-2-carboxylic acid ethyl ester 5 Tea solution of 1.0g1H-indote-2-carboxylicacid ethyl ester In 10 ml N,N-dimethylformamide 0.14 g sodium hydride were added at 0°C After stirring for 30 min 1.58 g2-bromo-N-{4-chloro- phenyl)-acetamide were added and the mixture was stirred for 2 hours at room temperature. After diluting with 15 ml water the mixture was filtered through a cherti elut® cartridge and the compound was eluted with ethyl acetate. After concentration under reduced pressure the 10 residue was directly subjected to the subsequent saponification reaction without further purification. Yield: 1.45 g. MS (ESH-): m/e = 357, chloro pattern. (ii) 1-[(4-Chioro-phenylcarbamoyl)-methyl]-1 H-indole-2-carboxylic acid 15 To a solution of 1.45 g 1-[(4-chloro-phenylcarbamoyl)-methyl]-1 H-indote-2-carboxylic acid ethyl ester in TOO ml tetrahydrofuran 30 ml water and 0.59 g potassium hydroxide.were added. After stirring for 2 hours at room temperature the reaction mixture was acidified with 6 N hydrochloric acid. The precipitate was collected by filtration and was washed with 20 ml water. The product was obtained as a white solid which was dried under reduced pressure. 20 Yield: 1.37 g. MS (ESi+): m/e = 329, chloro pattern. 1H-NMR (400 MHz, DMSO/TMS): 5 =10.50 (s, 1H); 7.70 (d, 1H); 7.61 (d, 2H); 7.58 {d, 1H); 7.37 (d, 2H); 7.32 (t, 1H); 7.25 (s, 1H); 7.14 (t, 1H); 5.44 (s, 2H). (iii) 1-[(4-Chloro-phenylcarbamoyl}-methyl]-1H-indole-2-carboxylic acid (3,4,5,6-tetrahydro- 2H-25 [l,4']bipyridinyM-ylmethyl)-amide TO a suspension of 50 mg 1-[{4-chIoro-phenylcarbamoy!)-methyl]-1 H-indole-2-carboxylic acid, 97 mg (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yI}-methylamineand 38.7 mg bis(2-oxo-3-oxazolidinyl)phosphinic chloride in 1 ml N,N-dimethylformamide 61.7 pi triethyiamine were added. After stirring at room temperature for 16 hours the solvent was removed under reduced 5 pressure and the residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid). The fractions containing the product were evaporated and lyophilized to yield a white solid. The product was obtained as its trifluoroacetate salt Yield: 6.9 mg MS (ES-^): m/e=: 502, chloro pattern. 10 1H-NMR (300 MHz. DMSO/TMS); 5 =13.14 (s; 1H); 10.45 (s, 1H), 8.63 (t, 1H); 8.17 (d, 2H); 7.64 (d, 1H); 7,61 (d, 2H); 7.56 (d, 1H); 7.38 (d, 2H); 7.26 (t, 1H); 7.17 (s, 1H); 7.12 (m, 3H); 5.43 (s, 2H); 4.13 (d,2H); 3.13 {m,4H);1.80(m,2H);1.21 (m,3H}. 15 Example 253: 1-[(4-chloro-phenylcarbamoyl}-methyl]-1H-indole-2-carboxylicacid (3,4,5,6-tetrahydro- 2H-[1,4']bipyridinyl-4-yl)-amide CI' The title compound was prepared analogously to example 252 with the difference that 3,4,5,6-Tetrahydro-2H-[1,4']bipyridinyl-4-ylamine was used instead of (3,4,5,6-tetrahydro-2H- 20 [l,4']blpyridinyl-4-yl)-methylamine. MS (ES+): m/e= 488, chloro pattern. 1H-NMR (300 MHz, DMSO/TMS): 5 =13.23 (s, 1H); 10.44 (s, 1H),8.43 (d, 1H); 8.23(d, 2H); 7.65 (d, 1H); 7.61 (d, 2H}; 7.56 (d, IH); 7.35 (d, 2H); 7.23 (m, 4H}; 7.12 (t, 1H); 5.44 (s, 2H); 4.20 (m, 3H); 3.32 (m, 2H); 1.95(m, 2H);1.58 (m, 2H). 25 Example 254: N-(4-chlQro-phenyl]-2-{2-[4-(pyridin-4-ylamino)-piperJdine-1-carbonyl]-indol-1-yl}- acetamlde N^ K^U N' N ci- The title compound was prepared analogously to example 252 by using Piperidin-4-yl-pyridin-4-yl-amine was used instead of {3,4.5,fr-tetrahydro-2H-[1,4']bipyridinyl-4-y[}-methylamlne. MS (ES+): m/e= 488, chloro pattern. 5 1W-NMR (300 MHz, DMSO/TMS); 6 =13.24 (s, 1H); 10.45 (s, 1H), 8.43 {d, 1H); 8.23 {d, 2H); 7.64 (d, 1H); 7.60 (d, 2H); 7.55 (d, 1H); 7.35 (d, 2H); 7.22 (m, 4H); 7.11 (t, 1H); 5.44 (s, 2H); 4.20 (m, 3H); 3.33 (m, 2H); 1.95 (m, 2H);1.57 (m, 2H). 10 Example 255: 1-[(4-chloro-phenylcarbamoYl)-methyl]-1H-indole-2-carboxylicacid (1-cydopropyl- piperidin-4-yl)-amide N M O.-^ 0 k .N N cr r The title compound was prepared analogously to example 252 with the difference that 1-Cyclopropyl-piperidin-4-ylamine was used instead of (3,4,5,6-tetr3hydro-2H-[1,4']bipyridinyl-4-15 yl)-methylamine. MS (K+): m/e= 451, chloro pattern. 1 H-NMR (300 MHz, DMSO/TMS): 5 =10.44 (s, 1H); 8.78 (s, 1H); 8.57 (d, 1H); 7.68 (d, 1H); 7.60 (d, 2H); 7.57 (d, 1H); 7.36 (d, 2H); 7.27 (t, 1H); 7.23 (s, IH); 7.12 (t, 1H); 5.44 (s, 2H}; 3.44 (m, 2H); 3.25 (m, 2H); 2.03 (m. 3H); 1.73 (m, 2H); 0.84 (m, 5H). 20 Example 256: N-(4-chloro-phenyl)-2-[2-(4-pyrrolidin.-1-yl-piperidine-1-carbonyl)-indol-1-yl]-acetamide The title compound was prepared analogously to example 252 with the difference that 4- Pyrrolidin-l-yl-piperidine was used instead of (3,4,5,6-tetrahydro-2H-[1,4']btpyridinyl-4-yi}- methylamine. MS (K"^}: m/e= 465, chloro pattern. 5 1H-NMR (300 MHz, DMSO^'MS): S =10.53 (s, IH); 9.64 (s, IH); 7.64 (d. IH); 7.57 (m. 3H); 7.36 (d, 2H); 7.26 (t, 1H); 7.13 (t, 1H); 6J6 (s, ,1H); 5.20 (s, 2H); 4.45 (s, 2H); 3.45 (m, 3H); 3.06 (m, 3H); 1.97(m, 7H);1.55{s,2H}. 10 Example 257: 1-[(4-chloro-phenylcarbamoyl)-methyl]-5-nitro-1H-indole-2-carboxylicacid (1-isopropyl- piperidin-4-yl)-amide o" N" O... ^ 0 "^ ^N N u CI The title compound was prepared in analogy to example 248 with the difference that 5-nitro-1 H-indole-2-carboxylic acid ethyl ester was used Instead of the unsubstituted 1 H-indole-2- 15 carboxylic acid ethyl ester. MS (ES+): m/e= 498, chloro pattern. 1H-NMR (300 MHz, DMSO/TMS): 5 =10.53 (s, IH); 8.98 (s, IH); 8.83 (d, IH); 8.74 [s, IH); 8.14 (d, 1H); 7.85 (d, 1H); 7.59 (d, 2H); 7.50 (s, 1H); 7.38 (d, 2H); 5.52 (s, 2H); 4.02 (m, 1H); 3.45 (m; 2H};' 3.07 (m, 2H); 2.03 (m, 3H); 1.81 (m, 2H); 1.25 (d, 6H). 20 Example 258: 5-amino-4-chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide 24.4 mg1-[5-{5-chloro-thiopheri-2-yl)-lsoxazol-3-ylmethyi]-5-nrtro-1H-indole-2-carboxylic add {l-isopropyl-piperidin-4-yl)-amide were added to a solution of 58.5 mg tin chloride dihydrate in 1 ml ethanol. 0.5 ml 12 N aqueous hydrochloric acid was added and the mixture was stirred 5 at room temperature for 16 hours. After cooling of the reaction mixture it was basified to pH 12 with saturated aqueous solution of sodium hydroxide and the product isolated by filtration. The product was obtained as a white solid which was dried under reduced pressure. Vield: 10.0 mg MS {ES+): m/e= 532, chloro pattern. 1H-NMR (300 MHz, DMSO/TMS}: 5 = 8.40 (d, 1H); 7.56 (d, 1H); 7.28 (d, 1H); 7.24 (d, 1H); 7.07 (s, 10 1H); 6.86 (d, 1H}; 6.54 (s, 1H); 5.83 (s, 2H); 4.97 (s, 2H}; 3.70 (m, 1H); 2.78 (m, 2H); 2.68 (m, 1H); 2.14 (m, 2H); 1.78 (m, 2H); 1.53 (m, 2H); 0.96 (d, 6H). Example 259: 1-[5-(5-chloro-thiophen-2-yI)-isoxazol-3-ylmethyl]-1H-indoIe-2-carboxylic acid (1-15 cyanomethyl-piperidin-4-yl)-amide N^^ N To a suspension of 50 mg 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1 H-indole-2- carboxyiic acid piperidin-4-ylamide In 1 ml ethanol 43.5 mg potassium carbonate, 14.5 pL triethylamine and 7.3 pi bromo-aceto nit rile were added. After stirring at room temperature for 20 16 hours the solvent was removed under reduced pressure and the residue was purified by preparative HPLC (CIS reverse phase column, elution with a water/acetonitriIe gradient with 0.1%trifluoroacetic acid). The fractions containing the product were evaporated and lyophilized to yield a white solid. The product was obtained as its trifluoroacetate salt. Yield: 13.8 mg MS (ES+): m/e= 480, chloro pattern. 1H-NMR (300 MHz, DMSO/TMS): 5 = 8.49 [d, IH); 7.67 (d, IH); 7.58 [d, 1H);7.55 (d, IH); 7.28 (t, 1H); 7^5 (d, IH); 7.22 {s, IH); 7.13 [t. IH); 6.59 (s, IH); 5.90 [s. 2H); 3.87 {m,3H); 3.00 (m, 2H}; 2.48 (m, 2H); 1.91 (m, 2H); 1.67 (m, 2H}. Example 260: l-[5-(5-chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic add [1-(2- hydroxy-ethyl)-piperidin-4-yl]-amide 10 The title compound was prepared analogously to example 259with the difference that 2- bromo-ethanol was used Instead of bromo-acetonitrile. MS (ES+): m/e= 485, chloro pattern 1H-NMR (300 MHz, DMSOn"MS): 6 = 9.35 (s, IH); 8.63 (m, IH); 7.68 (d, 1H);7.61 (d, IH); 7.55 (d, 15 IH); 7.30 (t, IH); 7.25 (m. 2H);7.14 (t, IH); 6.59 [s, IH); 5.90 (s, 2H); 5.33 (s, IH); 4.04 (m, IH); 3.76 (m, 2H); 3.56 (m, 2H); 3.33 (m, 2H}; 3.12 (m, 2H); 2.02 (m, 2H); 1.87 (m, IH); 1.73 (m, IH) Example 261: 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethYl]-1H-indaie-2-carboxylicacid [1- 20 (2-methoxy'ethyl)-piperidin-4-yl]-amide The title compound was prepared analogously to example 259with the difference that 1-bromo-2-methoxy-ethane was used instead of bromo-acetonitrile and acetonitrile as solvent. MS (ES+): m/e= 499, chloro pattern. 1H-NMR(300 MHZ, DMSO/TMS): 5 = 9.30 (s, 1H); 8.65 (d, 1H); 7.68 (d, 1H}; 7.60 (d, IH); 7.54 {d. 1H); 7.30 (t, 1H); 7.25 (m. 2H); 7.15 (t, 1H); 6.58 (s, 1H); 5.90 (s, 2H); 4.02 (m, 1H); 3.67 (t, 2H); 3.54 (m, 2H); 3.33 (s, 3H); 3.28 (t, 2H); 3.10 {m. 2H]; 2.04 (m, 2H); 1.83 (m, 2H}. 5 Example 262: l-[5-(5 To a suspension of 50 mg 1-[5-(5-chloro-thiophen-2-yI)-isoxazo!-3-ylmethyI]-1H-indole-2-10 carboxylic acid piperidin-4-ylamide in 1 ml acetonitrile42.4 pi ethyl-diisopropyl-amineand 29.4 mg 2-chloro-acetamide were added. The reaction mixture was stirred at 80°C for 3 hours. After removal of the solvent under reduced pressure the residue was purified by preparative HPLC (CIS reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid). The fractions containing the product were evaporated and lyophilized to 15 yield a white solid. The product was obtained as its trifluoroacetate salt. MS (ES+): m/e= 498, chloro pattern. 1 H-NMR (300 MHz, DMSO/TMS): 6 = 9.62 (s. 1H); 8.65 (d, IH); 7.94 (s, 1H); 7.68 (m, 2H); 7.60 (d, 1H); 7.54 (d, IN); 7.28 (t, IH); 7.25 (m, 2H); 7.15 (t, 1H); 6.58 (s, IH); 5.90 (s,2H); 4.00 (m, IH); 3.88 (m, 2H); 3-53 (m. 2H); 3.16 (m, 2H); ZOO (m, 4H). 20 Example 263: 1-[5-(5-chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1H-indole-2-carboxylic acid (1- methylcarbamoYlmethyl-piperidin-4-YO-amide ci -s The title compound was prepared analogously to example 262with the difference that 2-chloro-N-methyl-acetamide was used instead of 2-chloro-acetamide. MS (ES^: m/e= 512, chloro pattern. 1H-NMR (300 MHz, DMSO/TMS); 5 = 9.74 (s, 1H); 8.65 (d, 1H); 8.45 (s, 1H); 7.68 (d, 1H); 7.60 (d, 1H}; 7.53 (d, 1H); 7.29 (t, 1H); 7.25 (m, 2H); 7.14 (t, 1H); 6.56 {s, 1H); 5.90 {s, 2H); 4.00 (m. 1H); 3.88 (m, 2H): 3.53 (m, 2H); 3.16 [m, 2H}; 2.69 (d, 3H); 2.04 [m, 2H); 1.92 (m, 2H). Example 264: 1-[5-[5-chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyi]-1H-indole-2 CI- ^s- 10 A solution of 50 mg 1-[5-{5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid piperidin-4-ylamidein 1.5 ml 1,2-dichloro-ethane was treated with 66.76 mg sodium triacetoxyborohydride, 18 pi glacial acid and 11.1 mg1H-imidazote-2-carbaldehyde. After stirring of the reaction mixture for 16 hours at room temperature the solvent was removed under reduced pressure. The residue was purified by preparative HPLC (C18 reverse phase 15 column, elution with a water/acetonitrlle gradient with 0.1% trifluoroacetic acid). The fractions containing the product were evaporated and lyophilized to yield a white solid. The product was obtained as its trifluoroacetate salt. MS (ES+}: m/e= 521, chloro pattern. 1H-NMR (300 MHz, DMSOn'MS): 5 = 8.54 (d. 1H); 7.68 (d, 1H); 7.58 (d, 1H); 7.53 (d, IH); 7.45 (s, 20 2H); 7.29 (t, IH); 7.25 (d, IH); 7.22 (s, IH); 7.14 (t, TH); 6.57 (s, IH); 5.90 [s, 2H); 4.13 (m, b); 3.87 (m, b); 3.18 (m, 2H}; 1.95 (m. 2H); 1.75 (m, 2H). Example 265:1-[5-(5-chloro-thIophen-2-yl)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxyllc acid [1-(1- methyl-1H-imida20l-2-ylmethyl)-piperidin-4-yl]-amide The title compound was prepared analogously to example 264with the difference that 1-methyl-1H-imida2ole-2-carbaldehyde was used instead of 1H-imidazoIe-2-carbaldehyde. MS (ES+): m/e= 535, chloro pattern. 1H-NMR (300 MHz, DMSO/TMS): 5 = 8.54 (d, 1H); 7.68 (d, 1H); 7.59 (d, 1H); 7.55 (d, 1H); 7.50 (s, 5 1H); 7^ (t, 1H); 7.25 (d, 1H); 7.22 (s, 1H); 7.14 (t. 1H); 6.57 (s. 1H); 5.90 {s. 2H): 4.13 (m, b); 3.93 (m, b); 3.78 (s, 3H); 3.23 (m, b); 1.95 {m, 2H); 1.75 (m. 2H}. Example 266: 1-[5-{5-chloro-thiophen-2-yl}-isoxazoI-3-y!methyl]-1 H-indoIe-2-carboxylic add [1-10 (2- dimethylamino-acetyl)-piperidin-4-yl]-amide A solution of 50 mg 1 -[S-(5-ch!oro-thtDphen-2-Yl)-isoxa2ol-3-y!methyl]-! H-indole-2-carboxylic acid piperidin-4-ylamide in 1 ml N,N-dimethy(formamide was treated with 29.0 mg potassium carbonate, 187.5 ^1 ethyl-diisopropyl-amine and 16.7 pi chloro-acetyl chloride. After stirring 15 oft the reaction mixture for 15 min at room temperature 19.5 mg dimethylamine hydrochloride were added and the mixture was further stirred at room temperature for 16 hours. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/acetonitrile gradient with 0.1%trifluoroacetic acid). The fractions containing the product were evaporated and 20 lyophiiized to yield a white solid. The product was obtained as its trifluoroacetate salt. MS (ES*): m/e= 526, chloro pattern. 1H-NMR(300 MHz, DMSO/TMS): characteristic protons for aromatic and amide moieties: 9.50 {s. 1H); 8.53 {d, 1H); 7.68 (d, 1H); 7.60 (d, 1H); 7.55 (d, 1H); 7.28 (t, 1H); 705 (d, 1H); 7.20 (s, 1H); 7.15(t, 1H);6.59(s, 1H). 25 Example 267: 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-Ylmethyl]-1H-indole-2-carbox7licadd [1-(2- amtnO'acetyl)-piperidin-4-yl]-amide [i){2-[4-({1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyi]-1H-indole-2-carbonyl>amino)-piperidin-1-yl]-2-oxo-ethyl}-carbamic acid tert.-butyl ester To a solution of 50 mg 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-yimethyl]-lH-rndole-2 [(ethoxycarbonyl) cyanomethylenamino]-N,N,N',N'- tetramethyluronium tetrafluoroborate were added and the mixture was stirred for 1 hour at room temperature. 15.2 mg tert.- butoxycarbonyla mi no-acetic acid were added to the mixture and the reaction rnixture was further stirred for 1 hour. After removal of the solvent under reduced pressure the residue was 10 purified by preparative HPLC {C18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid). The fractions containing the product were evaporated and Iyophilized to yield a white solid. The product was obtained as its trifluoroacetate salt. Yield: 22.0 mg MS (ES+): m/e= 598. 15 (ii) 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-yImethyi]-1H-indole-2-carboxylicacid [l-(2-amino- acetyl)-piperidin-4-yl]-amide A solution of 22.0 mg{2-[4-({1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2- carbonyl}-amino)- piperidin-1-yl]-2-oxo-ethyl}-carbamic acid tert.-butyl ester in 5 ml of a 8 N solution of hydrochloric acid In methanol) was stirred at room temperature for 16 hours. ID 20 ml water was added to the reaction mixture and the resulting mixture was Iyophilized to yield a white solid. The product was obtained as its hydrochloride salt. MS (ES-*-): m/e= 498, chloro pattern. IH-NMR (300 MHz, DMSO/TMS): 5 =8.54 (d, IH); 8.03 (m, 2H); 7.68 (d, IN); 7.59 (d, IH); 7.55 (d. IH); 7.28 (t, IH); 7.25 (d, IH); 7.22 (s, IH); 7.13 (t, IH); 6.59 (s, IH); 5.90 (s. 2H); 4.35 (m, IH); 25 4.07 (m, 1H); 3.95 (m, 1H); 3.87 (m, 1H); 3.73 (m, 1H); 3.16 (m, 1H); 2.86 (m, 1H); 1.90 (m, 2H); 1.54 (m ,1H); 1.44 (m,lH). Example 268: 1-[5-[5-ChIoro-thiophen-2-yI)-isoxazol-3-ylmethyi]-2-(1-isopropyl-piperidin-if-ylcarbamoyl)-1H-indole-5-carboxylicacid 1-ethoxycarbonyloxy-ethyl ester O I O N—( N- To a solution of 0.39 g 1-[5-(5-Chloro-thiophen-2-yl}-isoxa2ol-3-ylmethyl]-2-(1-isopropyl- 5 piperidln-4- ylcarbamoyl)-1H-indole-5-carboxylic acid hydrochloride in 15 ml DMF 0.23 g KI, 0383 g K2C03and 0.37 ml 1-chloroethyl-ethylcarbonate were added and the reaction mixture was stirred for 3h at GCC in an argon athmosphere. After filtration and removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLCeluting with a gradient of 0-100 % acetonJtrile in water (+ 0.01% trifluoroacetic acid). After addition of 1 M 10 hydrochloric acid and lyophilization in an acetonitrile/water mixture, the product was obtained as its hydrochloride. Yield: 0,33 g MS {ESI+): m/e = 643, chloro pattern. Example 269: 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin^-15 ylcarbamoyl)-1H-indole-4-carboxylicacid 1-ethoxycarbonyloxy-ethyl ester To a solution of 0.6 g 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4- ylcarbamoyl)-1 H-indole-4-carboxylic acid hydrochloride in 20 ml DMF 0.679 g KI, 20 1.13 g KzCOaand 1.094 ml 1-chloroethyl-ethy!carbonate were added and the reaction mixture was stirred for 3h at 60°C in an argon athmosphere. After filtration and removal of the solvent under reduced pressure the residue was directly purified by preparative RP-HPLC eluting with z gradient of 0-100 % acetonitrile in water {+ 0.01% trifiuoroacetic acid}. After addition of 1 M hydrochloric acid and lyophllization in an acetonitrile/water mixture, the product was obtained as its hydrochloride. Yield; 0,56 g MS (ESI+): m/e = 643, chloro 5 pattern- Example 270: 1-[S-(5-Giloro-thiophen-2-yI)-isoxazol-3-ylnriethyl]-2-(1-isopropyl'piperidin-4-ylcarbamoyl)-1H-indole4-carboxylic acid 2,2-diniethyi-propionyloxymethyl ester Q O 10 To a solution of 0,6 g 1-[5-(5-Chloro-thiophen-2-yl}-isoxazol-3-ylmethyl]-2-[l-isopropyl- piperidin-4- ylcarbarnoyI)-1H-indole-4-carboxylic acid in 20 ml DMF 0,319 g2,2-Dimethyl- propionicacid chloromethyl ester and 441 \i\ NEta were added and the reaction mixture was stirred for 5h at 60 °C . Then additional 0,16 g 2,2-Dimethyl-propionic acid chloromethyl ester 15 and 147 \i\ NEtj were added and the reaction mixture was stirred for 6h at 60 "C After removal of the solvent under reduced pressure the residue was dissolved in CHzCband the solution was washed with water. The phases were separated and the organic phase (after drying over Na2S04) was concentrated in vacuo. The residue was purified by preparative RP-HPLC eluting with a gradient of 0-100 % acetonitrile in water (-i- 0.01% trifiuoroacetic acid). After addition of 20 1 M hydrochloric acid and lyophllization in an acetonitrile/water mixture, the product was obtained as its hydrochloride. Yield: 0,5 g MS (ESH-): m/e = 641, chloro pattern. Example 271: 1-[5-(5-Chloro-thiophen-2-yl}-iSOxazol-3-ylmethyl]-2-{1-isopropyl-piperidin^-25 ylcarbamoyl)-1H-indole-5-carboxytic acid 1-{2,2-dimethyl-propionyloxy)-ethyl ester Ill To a suspension of 0.5 g 1-[5-(5-ailoro-thiDphen-2-y!}-isoxazol-3-ylmethyr|-2-(1-isopropyl-piperidin-4- yicarbamoyl}-! H-indole-5-carboxylic acid in 30 ml acetone 531 ti\ DBU were added and the mature was stirred forlSmin. at room temperature. To this solution 0,556 g 2^-5 Dimethyl-propionic acid 1-bromo-ethyl ester (prepared as described by E. Defossa et a!., Liebigs Ann. 1996,1743-1749) was added and the reaction mixture stirred for 4h at room temperature. Then addttional 266 p\ DBU and 0.185 g 2,2-Dimethyl-propionic acid 1-bromo-ethyi ester were added. After 16h at room temperature the mixture was concentrated in vacuo and the residue purified by preparative RP-HPLC eluting with a gradient of 0-100 % acetonitrile In water {+ 10 0.01% trifluoroacetic acid). After addition of 1 M hydrochloric acid and lyophilizatjon in an acetonitriJe/water mixture, the product was obtained as its hydrochloride. Yield: 0,48 g MS (ESH-): m/e = 655, chloro pattern. 15 Example 272: 1-[5-(5-Qiloro-thiophen-2-yl)-isoxazol-3-ylmethyI]-2-(1-isopropyl-piperidin-4-ylcarbamoyl}-1 H-indole^t-carboxyllc add 1-(2,2-dimethyl-propionyloxy)-ethyl ester N O o j O a To a suspension of 0.427 g l-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin^-ylcarbamoyl)-1H-indo!e-4-carboxylicacid in 30 ml acetone 453 ii\ DBU were added 20 and the mixture was stirred for 15 min. at room temperature. To this solution 0,475 g 2,2-Dimethyl-propionic acid 1-bromo-ethyl ester (prepared as described by E. Defossa et al., Liebigs Ann. 1996,1743-1749) was added and the reaction mixture stirred for 4h at room temperature. Then additional 227 yl DBU and 0.158 g 2^-Dimethyl-prop ionic acid l-bromo-ethyl ester were added. After 16h at room temperature the mixture was concentrated in vacuo and the residue purified by preparative RP-HPLCeluting with a gradient of 0-100%acetonitrilein water(-l-0.01% trifluoroacetic acid). After addition of 1 M hydrochloric acid and lyophili2ation in an 5 acetonitrite/water mixture, the product was obtained as its hydrochloride. Yield: 0,4 g MS (ESI+): m/e = 655, chloro pattern. BQmple273: 1-[5-{5-Chioro-thiophen-2-yl)-isoxazol-3-ytmethyl]-2-(1-isopropyl-piperidin-4-10 ylcarbamoyl)-1 H-indole-5-carboxylic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl 0 ° can be prepared from 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-YimethYll-2-^1-isopropyl-piperidin-4- yIcarbamoyl)-1 H-indole-5-carboxylic acid and 4-Chloromethyl-5-methyl-15 [1,3]dioxol'2-one by the procedure described by H. Yanagisawa et al., J. Med. Chem. 1996, 39, 323-338. Example 274: 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ZO ylcarbamoyl)-1H-indole-4-carboxylic acid 5-methyl-2-oxo-[1,3]dioxoM-ylmethyl 0-; O-^ II I V^ / N- can be prepared from 1-[5-{5-Chioro-thiophen-2-yl)-isoxazol-3-yimethyi]-2-{1-isopropyl-piperidin-4- y I carbamoyl)-! H-indole-4-carboxylic acid and 4-Chloromethyl-5-methyl- [13]dioxol-2-one bythe procedure described by H.Yanagisawa etal.j! Med. Chem. 1996,39, 323-338. Example 275: 1-[5-{5-Gh!oro-thiophen-2-ylHsoxazol-3-ylmethyl]-2-{1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-5-carboxylicacid 1-cyclohexyloxycarbonyloxy-ethyl ester 10 can be prepared from 1-[5-(5-Chloro-thiophen-2-yl)-isoxazo!-3-ylmethvl]-2-{1-i5opropyl-piperidin-4- ylcsrbamoyi)-! H-indole-5-carboxylic acid and cyclohexyl l-chloroethy! carbonate by the procedure described by K. Kubo et al., J. Med. Oiem. 1993,36, 2343-2349. 15 Example 276: 1-[5-{5-Chioro-thiophen-2-yI)-isoxazol-3-ylmethyl]-2-(1-i5opropyl-piperidin^-ylcarbamoyl)-1 H-indole-4-carboxylic acid l-cyclohexyloxycarbonyloxy-ethyl ester Cxx^J o 0 20 can be prepared from 1-[5-(5-Chloro-thiophen-2-Yl)-isoxazol-3-ylmethy!]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-iH-indDle-4-carboxylic acid and cyclohexyl 1-chloroethyl carbonate by the procedure described by K. Kubo et al., J. Med. Chem. 1993, 36, 2343-2349. Pharmacological testing T^ie ability of the compounds of the formula 1 to inhibit factor Xa or factor Vila or other enzymes like thrombin, plasmin, or trypsin can be assessed by determining the concenb^tion of the compound of the formula I that inhibits enzyme activity by 50 %, i. e. the ICso value, 5 which was related to the inhibition constant Ki. Purified enzymes were used in chromogenic assays- The concentration of inhibitor that causes a 50 % decrease in the rate of substrate hydrolysis was determined by linear regrsston after plotting the relative rates of hydrolysis (compared to the uninhibited control) versus the log of the concentration of the compound of, formula I. For calculating the inhibition constant Ki, the iCso value was corrected for 10 competition with substrate using the formula Ki = ICso / {1 + {substrate concentration / Km)} wherein Km is the Michaelis-Menten constant (Chen and Prusoff, Biochem. Pharmacol. 22 (1973), 3099-3108; I. H. Segal, Enzyme Kinetics, 1975, John Wiley & Sons, New York, 100-125; which were incorporated herein by reference). 15 a) Factor Xa Assay In the assay for determining the inhibition of factor Xa activity TBS-PEG buffer (50 mM Tris-HCl, pH 7.8, 200 mM Naa, 0.05 % (w/v) PEG-8000, 0-02 % (w/v) NaNa) was used. The ICso was determinedby combining in appropriate wells of a Costar half-area microtiter plate 25 M' human factor Xa {Enzyme Research Laboratories, Inc.; South Bend, Indiana) in TBS-PEG; 40 pi 20 I0%(v/v) DUSO inTBS-PEG(uninhlbitedcontrol)orvariousconcentrationsof the compound to be tested diluted in 10 % (v/v) DMSO in TBS-PEG; and substrate S-2765 {N(a)-benzyloxycarbonyl-D-Arg-Gly-L-Arg-p-nitroanllide; KabI Pharmacia, Inc.; Franklin, Ohio) in TBS-PEG. The assay was performed by pre-incubatingthe compound of formula I plus enzyme for 10 min. Then the assay was initiated by adding substrate to obtain a final volume of TOO pi. The 25 Initial velocity of chromogenic substrate hydrolysis was measured by the change in absorbance at 405 nm using a Bio-tek Instruments kinetic plate reader (Ceres UV900HDi) at 25 °C during the linear portion of the time course (usually 1.5 min after addition of substrate). The enzyme concentration was 0.5 nM and substrate concentration was 140 pM. b) Factor Vila Assay 30 The inhibitory activity towards factor Vila/tissue factor activity was determined using a chromogenic assay essentially as described previously (j. A. Ostrem et at., Biochemistry 37 (1998) 1053-1059 which Was incorporated herein by reference). Kinetic assays were conducted WE CLAIM: 1. A compound of the formula 1 wherein R1is 1. a monohydric or bicyclic 6- to 14-memberecl aryl, mono-, di- or trisubstituted independently of one another by R1, 2. a monocyclic or bicyclic 6-to 14-membered heteroaryl out of the group pyridyl, pyrimidinyl, indolyl, isoindolyl, indazolyl, phthalazinyl, quinolyl, isoquinotyl, benzothiophen, quinazolinyl and phenyipyridyl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R*, or 3. a monocyclic or bicyclic 5- to 14-membered heteroaryl, containing one, two, three or four heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said heteroaryl Is unsubstituted or mono-, di- or trisubstituted independently of one another by R*, and which is additionally substituted by a monocydic or bicyclic 5- to 14-membered heteroaryl, which is as defined above, wherein heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R1, provided that R° is not phenyl when Q is a dired bond, R1 is 1. halogen, 2. -N02, 3. -CN, 4. -C(0)-NHj, 5. -OH, 6. -NHa, 7. -OCF3 8. a monocyclic or bicyclic 6- to 14-membered aryl, wherein aryl is mono-, di- or trisubstituted independently of one another by halogen or -0-(Ci-C8)-alkyl, 9. -(Ci-CB)-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, NH2, -OH or a methoxy residue, or 10. -0-(Ci-Ca)-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, NHj, -OH or a methoxy residue, provided that R1 is at least one halogen, -C(0)-NH2 or -0-(Ci-C8)-alkyl residue, if R° is a monocyclic or bicyctic 6- to 14-membered aryl, O is a direct bond, -C(0)-; -{Co -C2)-alkylene-C(0)-NR'°-, -NR'°-C(0)-NR1°-, -NR1°-C(0)-, -SO2-, -(Ci-C6)-alkylene, wherein alkylen is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, -NHj or -OH; or -(Ca-Cej-cycloalkylene, wherein cycloalkylene is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, -NH2 or -OH; R1 is a hydrogen atom, -(Ci-C4)-alkyl, wherein alkyl is unsubstituted or substituted one to three times by R11 or a monocyclic or bicyclic 5- to 14-membered heteroaryl as defined above, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R11, R1is a direct bond or-(Ci-C4)-alkylene, or R1 and R' together with the atoms to which they are bonded can form a 4- to 7- membered cyclic group, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic group is unsubstituted or mono-, di- or trisubsfitufed independently of one another by R'*, R1-N-R1-V can form a 4- to 7-membered cyclic group, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted independently of one another by R'\ R" is halogen, -OH, =0, -(CrCB)-alkyl, -(Ci-C4)-alkoxy, -NO2, -C(0)-OH, -CN, -NH2, -C(0)-0-(Ci-C4)-alkyl, -(Ci-CeHlkyisulfonyl, -SO1, -C(0)-NH-{C,-CB)-alkyl, -C(0)-N-[(Ci-C8)-alkyl]j, -NR1°-C(0)-NH-(C,-C8)-alkyl, -C{0)-NH21 -SR1°, or -NR"'-C{0)-NH-[(Ci-CB)-alkyl]2, wherein R1° is hydrogen atom, -(Ci-C3)-perfluoroalkyl or-(CrC6)-alkyl, V is 1. a 3- to 7-membered cyclic residue, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-, di- or trisubstituted independently of one another by R1", 2, a 6- to14-membered aryl, wherein aryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R'*, or 3. a monocyclic or bicyclic 5- to 14-membered heteroaryl as defined above, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R", 10 provided that V is not 1,3-thiazole when G is -(CHj)_1-C(0)-NR "(CHj)1- and m is zero, or provided that V is not tetrazoie when G is a direct bond and M is hydrogen atom, G is a direct bond, -(CH2)1-NR1°-S02-NR1°-{CH2)„-, '{CH1-CHiOHHCHX-. -(CH1)1-, -(CH1)1-O-(CH1)1-, -{CH,VC{0)-NR'°-(CH,)1-, -(CH,)-S02-{CH1)1-, -{CH1)1-NR"'-C(O)-NR1'-(CH11-,-{CH1)1-NR'°-C(0HCH;„-,-(CH1)1-C(O)-(CH1)1-, -{CHP-S-(CH1)1-,-{CH,)„-SO1-NR"-(CH,)„-,-(CH;1-NR'°-SO,-(CH,)„-, -(CH,)1-NR'°-, -(CH1)1-0-C(0)-NR'°-{CH,)1- or -(CH1)1-NR'°-C(0)-0-(CH1)„-, n and m are are independently of one another identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6, R1° is hydrogen atom, -(Ci-C3)-perfluoroalkyl or -(C,-C6)-alkyl, M is 1. a hydrogen atom, 2. -{CrCa)-alkyl, wherein aikyi is unsubstituted or mono-, di- or trisubstituted independently of one another by R'*, 3. -C(0)-NR11Ri=, 4. -(CHP1-NR", 5. -(Ce-Ci4)-aryl, wherein aryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R1*, 6. -(C5-Ci4)-het6roaryi, wherein heteroaryl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently of one another by R'1*, 7. {C3-C7)-cycloalkyl, wherein said cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R1*, or 8. a 3- to 7-membered cyclic residue, containing up to 1. 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyciic residue js unsubstituted or mono-, di- or trisubstituted independently of one another by R1*, wherein R1* is defined above, R" and R11 are independently of one another identical or different and are 1. hydrogen atom. 2. -(Ci-C6)-alkyl, wherein alkyl Is unsubstituted or mono-, di- or thsubstituted independently of one another by R", 3. -(C6-Ci4)-aryl-(Ci-C4)-alkyl-, wherein alkyl and aryl independently from one another are unsubstituted or mono-, di- or thsubstituted by R11, 4. -(Ce-CiO-aryl-, wherein aryl is unsubstituted or mono-, di- or thsubstituted independently of one another by R", 5. -(C5-Ci4)-heteroaryl, wherein heteroaryl as defined above and is unsubstituted or mono-, di- or thsubstituted independently of one another by R1' or 6 - (C5-Ci4)-heteroaryl-(Ci-C4)-alkyl-, wherein heteroaryl is as defined above and wherein alkyl and heteroaryl Independently from one another are unsubstituted or mono-, di- or thsubstituted by R11, R" and R11 together with the nitrogen atom to which they are bonded can form a saturated 5- to 7-membered monocyclic heterocyclic ring which in addition to the nitrogen atom can contain one or two Identical or different ring heteroatoms chosen from oxygen, sulfur and nitrogen; wherein said heterocyclic ring Is unsubstituted or mono-, di- or trisubstituted independently of one another by R1', R'1ls halogen, -NO;, -CN, =0, -OH, -(Ci-CB)-alkyl, -(Ci-Cs)-alkoxy, -CFj, phenyl, phenyloxy-, -C(0)-0-R", phenyl-{Ci-C4)-alkoxy-, -C(0)-N-R11R'1, -NR"R'1 -NR"'-S0z-R'°, -S-R'°, -SOn-R1°, wherein n is 1 or 2, -SOj-NR1R'1 -C(0)-R'°,-(Co-C4)-alkyl-C(0)-0-C(R'1R1VO-C(0)-R11 -(Co-C4)-alkyl-C(0)-0-C(R'R1')-0-C{0)0-R11, or a residue of formula Va, -{Co-CJ-all below, R11 and R'1 are independently of one another hydrogen, -(Ci-C6)-alkyl, or together with the cartion atom to which they are bonded they can form a 3- to 6 membered carbocyclic ring which is unsubstituted or substituted one to three times by R'", R" is -(Ci-C6)-alkyl, -(C,-C8)-cycloalkyl, -(Ci-C6)-alkyt-(Ci-C8)-cycloalkyl, wherein said cycloalkyi ring is unsubstituted or substituted one to three times by R'°, and R1, R*, R1 R* and R1 are independent of one another are identical or different and are a) hydrogen atom, b) halogen. c) -(Ci-C4)-aikyl, wherein alkyl is unsubstituted or substituted one to three times by R", d) -(C, -CaVperfluoroalkyI, e) phenyl, wherein phenyl is unsubstituted or substituted one to three times by R11 f) -0-(Ci-C4)-alkyl, wherein alkyl is unsubstituted or substituted one to three times by R11, g) -NO2. h) -CN, i) -OH, j) phenytoxy-, wherein phenyloxy is unsubstttuted or substituted one to three times by R11 jj) benzyloxy-, wherein benzyioxy is unsubstituted or substituted one to three times by R", k) -C(0)-0-R1\ wherein R" is as defined above, I) -C(0)-N-R"R1= , wherein R" and R11 are as defined above, m) -NR11R11 wherein R1' and R11 are as defined above, n) -NR1°-S02-R1°, wherein R'° is as defined above, o) -SR'0, wherein R1° Is as defined above, p) -SOn-R1°, wherein n is 1 or 2 and R1° is as defined above, q) -S02-NR11R11 wherein R" and R11 are as defined above, r) -CCO-R1", wherein R'° is as defined above, s) -C{O)-O-C(R11R1>O-C(0)-R11 wherein R1*, R11 and R" are as defined above, t) -C(0)-0-C(R1'R1«)-0-C(0)0-R11 wherein R11 R'1 and R11 are as defined above, u) a residue of formula Va, v) a residue of formula Vb or Vc, o O If Vc 0= Vb O ,N N1 >=N w) -NR1'-{Ci-C4)-alkyl, wherein alkyi is unsubstituted or substituted one to three times by R11 x) -O-CF3, or y) a residue from the foUowng list H -1 .s. O " O HO 1 N-S N-0 N-S 0 A N-'1-N N fiH J1 / N-N and ' "1 N-H wherein R1°, R1\ R'1 and R11 are as defined above, provided that 2-benzoxazolecarbcxyllc acid, 6-[[[5-[[(1,1-dimethylethoxy)carbonyl] amino]-1-[(4-methoxyphenyl)methyl]-1H-indol-2yl]cart>onyl]amino]-, methyl ester is excluded in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts. 2. A compound of the formula I as claimed in claim 1, wherein R° is 1. phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted Independently of one another by R*, 2. a bicyclic 5- to 14-membered heteroaryl selected out of the group indolyl, isoindolyl, benzofuranyl, benzothiophenyl, 1,3-benzodioxolyl, indazolyl, benzimidazoiyi, benzoxazolyl, benzothiazolyl, quinolinyl, isoqufnolinyl, chromanyl, isochromanyl, cinnolinyl, quinazollnyl, quinoxalinyl, phthalazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, purinyl and pteridinyl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R°, and in addition is substituted by a residue selected out of the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyiTolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, , triazolyl, isothiazolyl, thiadiazolyl, tetrazolyl, pyrimidinyl, pyridazinyl and pyrazinyl, wherein said residue is unsubstituted or mono-, di- or trisubstituted independently of one another by R® 3. a monocyclic 5- to 14-membered heteroaryl out of the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2- furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, Isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R°, and in addition is substituted by a residue selected out of the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothlazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein said residue is unsubstituted or mono-, di- or trisubstituted independently of one another by R* provided that R° is not phenyl virtien Q is a direct bond, R1 is 1. halogen, out of the group F, CI, Br or J, 2. -C(0)-NH2, 3. -(Ci-C4)-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, -OH or a methoxy residue, or 4. -0-(Ci-C4)-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen or a methoxy residue, provided that R1 is at least one halogen, -C(0)-NH2 or -0-(Ci-C4)-alkyl residue, if R° is phenyl, Q is a direct bond, -C(0)-; -S02-, -(Ci-CeJ-alkylen or -{CD -C2)-alkylen-C(0)-NR1°-, R1 is hydrogen atom or -{Ci-C2)-alkyl, R1is a direct bond or -(C1-C2)-atkyfen, or R1-N-R1-V can fonn a 5- to 7- membered cyclic group out of the group piperidine, piperazrne, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazlne, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, ketopiperazlne, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted independently of one another by R1", R'" is halogen, -(Ci-C4)-alkyl or -NH;, V is 1. a 3- to 7-membered cyclic residue out of the group aziridine, azinne, azetidine, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole, 1,2,3-tria2ole, 1,2,4-triazole, tetrazole, pyridine, pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, tetrazine, tetrazole, azepine, diazirine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, pyridazine, piperidine, piperazlne, pyrrolidinone, ketopiperazlne, furan, pyran, dioxole, oxazole, isoxazole, 2-isoxazoline, isoxazolidine, morpholine, oxirane, oxaziridine, 1,3-dioxolene, 1,2-oxaiine, 1,3-oxazine, 1,4-oxazine, oxaziridine, thiophene, thiopyran, thJetan, thiazole, isothiazole, isothiazoline, isothiazolidine, 1,2-oxathiolan, thiopyran, 1,2-thiazine, 1,3-thJazole, 1,3-thiazine, 1,4'thiazine, thiadiazine orthiomorpholine, wherein said cyclic residue is unsubstituted or mono-, di- or trisubstituted independently of one another by R'1 2. phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R", or 3. a bicyclic 5- to 14-membered heteroaryl out of the group quinolyl, isoquinolyl and quinoxalinyl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R", provided that V is not tetrazole when G is a direct bond and M is hydrogen atom, G is a direct bond. -(CH1)1-, or -(CHJ,)1-NR"'-, m is the integers zero, 1. 2, 3 or 4, R1°is hydrogen atom, -(Ci-C3)-perfluoroaltcyl or-(Ci-C1)-alkyl, M is 1. a hydrogen atom, 2. -(C6-Ci4)-heteroaryl, wherein heteroaryl is a residue out of the group piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrclidinone, pyridonyl, imidazole, pyridazine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepin6, 1,3-diazepine, 1,4-diazepine, azepine, Itetopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline. morpholine, thiazole, isothiazole, tetrahydropyran, thiadiazole or thiomorpholine, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R", 3. -(C,-C8)-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R", or 4. (C3-C6)-cycloalkyl, R1, R*, R1, R* and R1 are independent of one another are identical or different and are a) hydrogen atom, b) F, CI, Br, c) -{Ci-C4)-alkyl, wherein alkyl is unsubstituted or substituted by R11, d) -CF3 e) phenyl, wherein phenyl is unsubstituted or substituted one to three times by R", f) -0-(Ci-C4)-alkyl, wherein alkyl is unsubstituted or substituted by R'1, g) -NO;, h) -CN, i) -OH, j) phenyloxy-, wherein phenyloxy is unsubstituted or substituted by R11, jj) benzyloxy-, wherein benzylcxy is unsubstituted or substituted by R11 k) -C(0)-0-R", I) -C(0)-N-R"R1=', m) -NR"R'1 n) -NR'°-S02-R'°, o) -SOn-R1°, wherein n is 1 or 2, p) -S02-NR"R11 q) -C(0)-R1°, r) -C(O)-O-C{R'*R1*)-0-C(O)-R". wherein R1*, R'1 and R11 are as defined above, s) -C(0)-0-C(R'R11)-0-C(0)0-R11 wherein R1', R11 and R11 are as defined above, t) a residue of foimula Va -(Co-C4)-alkyl-C(0)0-(C,-CJ-alkyl—L.0 Va u) a residue of formula Vb or Vc, 0 O. 1 //• Vb O 1N vc V) -O-CF3, or w) a residue from the following list A. .OH 9 .OMe V"V».V".HVX R'1 is halogen, -NO2, -CN, =0, -OH, -(Ci-Ca)-alkoxy, -CF3, -C(0)-0-R", -C{0)-N-R"R11, -NR11R'1 -NR11-SOrR1", -SOn-R", wherein n is 1 or 2, -S03-NR"R11-C(0)-R1°,-(Co-C4)-alkyl-C(0)-0-C(R'1R'1)-0-C(0)-R'1 -(Co-CO-alkyl-C(0)-0-C(R1*R11)-0-C(0)0-R", or a residue of fomiula Va, wherein R'", R'1R'1R11 R1" or R1'are as defined above, in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts. A compound of the formula I as claimed in claim 1 or claim 2, wherein R" is 1. phenyl, wherein phenyl is unsubstituted or mono- or disubstituted independently of one another by R1, 2. a monocyclic 5- to 14-membered heteroao' out of the group thieny}, thiadiazolyl, isoxazclyl and thiazolyi, wherein said heteroaryl Is substituted by a residue selected out of the group thienyl, 2-thienyl and 3-thienyl, wherein said residue is unsubstituted or mono- or disubstituted independently of one another by R1 provided that R° is not phenyl when Q is a direct bond, R1 is F, CI, Br, -O-CHa, -C(0)-NH2 or -O-CF3, provided that R" is at least one halogen, -C(0)-NH2 or -0-CHa residue, if R° is phenyl, is a direct bond, -C(0)-, -SO2-, methylene or ethylene, R1 is hydrogen atom, R1 is a direct bond or methylen. or R'-N-R1-V can form a 5- to 7-membered cyclic group out of the group pyrrolidine, piperidine and piperazine, R1' is -C(0)-0-R", -C(0)-N-R1'R11, -NR"R1=, -NR1°-S02-R'1 -SOn-R1°, wherein n is 1 or 2, -SOj-NR1'R'1 -C(0)-R'°, -(Co-C1)-alkyl-C(0)-0-C(R'*R1*')-0-C{0)-R'1 -(Co-C4)-alkyl-C(0)-0-C(R"R'1)-0-C{0)0-R1', or a residue of formula Va, -(C(,-C4)-alkyl-C(0}0-CHj—110 11 wherein R'", R",R'1R'1 R'" or R'1are as defined above, R" is halogen, methyl, ethyl or -NH2, V is 1. a residue out of the group containing isoquinoline, quinolline, quinazoline, piperidine, azetidine, tetrahydropyrane, piperazine and isoxazole, wherein said cyclic residue is unsubstituted or mono- or disubstituted independently of one another by R1*, or 2. phenyl, wherein phenyl is unsubstituted or mono- or disubstitirted independently of one another by R", G is a direct bond, -(CH1)1- or -{CHJ)_1-NR'°-. m is the integers zero, 1 or 2, R1° is hydrogen atom or -(CrC4)-alkyl, M is a hydrogen atom, (C2-C4)-alkyl, imidazolyl, pyrazolyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl, or (Cj-Cej-cycIoaikyJ, wherein said cyclic residues are unsubstituted or mono- or disubstituted independently of one another by R'*, R1, R\ R1 R1 and R' are independent of one another are identical or different and are a) hydrogen atom, b) F, CI, c) -(Ci-C4)-alkyl, wherein alkyl is unsubstituted or substituted by R11 d) phenyl, wherein phenyl is unsubstituted or substituted one to three times by R", e) -0-{Ci-C4)-alkyl- wherein alkyl is unsubstituted or substituted by R11, 0 -C(0)-0-R", g) -C(0)-N-R11R'1 h) -NR"R11 i) -NR1-SOz-R'", j) -S02-NR"R11 k) -C(0)-R'° I) -C(0)-0-C(R11R'*')-0-C(0)-R", wherein R11 R'1 and R1' are as defined above, m) -C(0)-0-C(R11R'1)-0-C(0)0-R'1 wherein R1', R'1 and R" are as defined above, n) a residue of formula Va 0) a residue of formula Vb or Vc, 'A >=1 p) a residue from the following list Q ,N ,sa jLySQ. 11 P •-. N' 1C„, - ~N CF3 _1 in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts. A compound of the formula I as claimed in one or more of claims 1 to 3, wherein the compound of the formula I is 1 -[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1 H-indole-2-carbDxylic acid {1 -isopropyl-pipefidin-4-yl)-amide, 1-I5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-5-methanesulfonyl-1H-indole-2- carboxyljc acid (1-isopropyl-piperidin-4-yl)-amide, l-[5-(5-Chloro-thiophen-2-yi)-isoxa2D)-3-ylmetby)J-5-nitro-1H-indo)e-2-carboxy)icacid {1-isopropyl-piperidin-4-yl)-amide, 5-Benzyloxy-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl}-1H-Jndole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-am(de, 5-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-lndole-2-carboxylicacid(1- isopropyl-piperidin-4-yl)-amide. 1-[5-(5-Chtoro-thiophen-2-yl)-isoxazol-3-ylmethyi]-5-methoxy-1H-indole-2-carboxyiic acid {1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-6-methoxy-1H-indole-2-carboxylicacid (1-isopropyi-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethy|]-5-methyl-1H-indole-2-carboxylic acid (1-isopropyi-piperidin-4-yl)-amJde, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4,6-dimethoxy-1H-indcle-2-carboxylic acid (1-isopropyl-piperidin-4-y[)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethy|]-5,6-dimethoxy-1H-indole-2-carbcxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yimethyl]-7-nitro-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide, 1-i5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethy|]-5-trlfluoromethoxy-1H-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yt)-amide, l-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1H-indole-2-carboxylic acid (1 -isopropyl-piperidin-4-yl)-amide, 1 -I5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyll-7-(2,2-dimethyl-propionylamino)-1H- indole-2-carboxylic acid (1-lsopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-methoxy-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-phenyl-1H-indole~2-carboxylic acid {1-isopropyl-piperidiri-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-6-hydroxy-5-methoxy-lH-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-y[)-lsoxazol-3-yimethyl]-4,6-difluoro-1H-indole-2-carboxylic acid (l-isopropyl-piperidin-4-yl)-amide, 4-Benzyloxy-1-[5-(5-chlo1o-thtophen-2-yl)-isoxazol-3-ylmelhyl]-1 H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-yl)-amide, 7-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyll-1 H-indole-2-carboxylic acid (1-isopropy|-piperidin-4-yl)-amide, 6-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indole-2-carboxy[ic acid {1-isopropyl-piperidin-4-y(}-amide, 1-[5-(5-Ch(oro-thiophen-2-yl)-isoxazol-3-ylmethy[]-5-ethyl-1 H-indole-2-carboxylic acid (1 -isopropyl-piperidtn-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-fluoro-1H-indole-2-carboxylic acid (1-isopropyt-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-nitro-3-phenyl-1 H-indoie-2- carboxylic acid (1 -isopropyl-piperidin-4-yl)-amide, 5-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-phenyl-1H-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yI)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylm6thyl]-5,7-drnuoro-1H-ind(1e-2-carboxy[ic acid (1-isopropyl-pip6ridin-4-yl)-amide, 1-[5-(5-Ch[oro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5,7-dinitro-1H-indol6-2-carbcxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-fhiophen-2-y/)-isoxazo/-3-ylmethy/11H-indole-2-ca1boxylic acid (3,4,5,6- tetrahydro-2H-(1,4']bipyridinyl-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethy|]-7-methyl-1 H-indole-2-carboxylic acid (3,4,5,6-tetrahydro-2H-I1,4']bipyridinyl-4-y[)- amide, 1 -[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-nitro-1 H-indole-2-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide, {1-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-ylmethyl]-1 H-indol-2-ylH4-(pyridin-4- ylamino)-piperidin-1 -yl]-methanone, {1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-yimethyi]-5-nitro-1H-indoi-2-ylH4-(pyridin-4-ylamino)-plperidin-1-yiI-methanone, {1-[5-(5-Chtoro-thiophen-2-1)-isoxazol-3-ylmethyl]-7-methyl-1 H-indol-2-yt}-[4-(pyridin- 4-ylamino)-piperidin-1 -yl]-methanone, {1 -[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1 H-indol-2-yl}-(4-isopropylamino-piperidin-1-yl)-methanone, {1-[5-{5-Chloro-thiophen-2-yl)-isoxazcl-3-ylmethyl]-7-methyl-1H-indoJ-2-yl}-(4-isoprcpylamino-piperidin-1-yl)-methanone, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethylI-1H-indole-2-carboxylic acid (1-ethyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1H-lndoie-2-carboxylic acid {1-ethyl-piperidin-4-yl)-amide, {H5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-(4-pyrrolidin-1-1- piperidin-1-yl)-methanone, [1,4'IBipiperidinyl-1'-yl-{1-[5-(5-chloro-thlophen-2-yl)-isoxazol-3-ylmethyl]-1H-lndol'2-yl}-methanone, 1-[5-{5-Chloro-tliiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxyllc acid (3- pyridin-4-yl-4,5-dihydro-isoxazol-5-ylmethyl)-amide, {1-[5-(5-Chloro-thiophen-2-yl)-isoxazoi-3-ylmethyl]-1H-indoi-2-y!H4-pyridin-4-ylmethyl-piperazin-1 -yl)-methanone, 1 -[5-(5-Chlorc-thlophen-2-y!)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid (1- isopropyl-piperidin-4-ylmethyl)-amide, 1-[5-(5-Chloro-thiophen-2-y!)-isoxazol-3-ylmethyl]-1H-indcle-2-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-ylmethyl)-amide, 1 -[5-(5-Chloro-thtophen-2-yl)-isoxazol-3-ylmethy[]-1H-indcle-2-carboxylic acid (1-cyclopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid [1- (tetrahydro-pyran-4-yl)-plperidin-4-yl]-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethy[]-lH-indole-2-caftoxylic acid (1- cyclopentyl-piperidin-4-yl)-amide, 1-l5-{5-Chioro-thioplien-2-yl)-isoxazDl-3-ylmethyl]-1H-indole-2-carboxylic acid (1- cyclofiexyl-piperidin-4-yl)-amide, 1-(3-Methoxy-benzyl)-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-y[)- amide, 1-(3-Methoxy-benzyl)-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-ylmethyl)- amide, 1-(3-Methoxy-benzyl)-1H-indole-2~carboxylic acid (3,4,5,6-tetrahydro-2H- [1,4']bipyridinyl-4-ylmethyl)-amide, (4-lsopropy!amino-piperidin-1-yl)-[1-{3-methoxy-benzyi)-1H-indol-2-yl]-methanone, 1-(3-Methoxy-benzyl)-1H-indole-2-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide, [1-(3-Methoxy-benzyl)-1H-indo[-2-yl]-[4-(pyridin-4-ylamino)-piperidin-1-yl]-methanone, 4-Methoxy-1-(3-methcxy-benzyl)-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)- amide, 5-Chloro-1-(3-methcxy-ben2yl)-1 H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yi)- amide, 6-Methoxy-1-(3-methoxy-benzyl)-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)- amide, 1-(3-Methoxy-benzyl)- 5-methyt-1H-indo(e-2-cart)Oxyl(c acid (1-(sopropyl-piperidin-4-yi)- amide, 5-Benzyloxy-1-(3-methoxy-ben2yl)-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4- yl)-amide, 1-(3-Methoxy-benzyl)-5-nitr(>-1H-indole-2-carboxylicacid(1-isopropyi-piperidin-4-yl)-amlde, 5-Methoxy-1-(3-methoxy-ben2yl)-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-y!)- amide, 1-phenyl)-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide, 1-(4-Chloro-phenyl)-1H-indoie-2-carboxylic acid {1-isopropy!-piperidin-4-yl)-amide, 1-(6-Chloro-benzo[bJthiophen-2-ylmethyl)-1H-indo!e-2-cart>oxylic acid (1-isopropyl- piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-1H-indole-2-carboxyiicacid (1-isopropyl-piperidin-4-yl)-amide, 1-t3-(5-Cliloro-thiophen-2-yl)-isoxazol-5-ylmethyl]-1H-indole-2-carboxylic acid (1-isDpropyl-piperidin-4-y);-am)de, 3-Chforo-1-[5-(5-chloro-thiophen-2-y))-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-yl)-amide, 3-Bromo-1-[5-(5-chiorc-thiophen-2-yi)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid (1 -isopropyl-piperidin-4-yl)-amide, 1-(4-Chioro-benzyl)-1H-indo!e-2-carboxy!ic acid (1-isoprDpy)-piperid/n-4-y))- amide, 1-(4-Ch)oro-ben2y))-1H-indo)e-2-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide, 1-(2,4-Dlchloro-ben2yl)-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)- amide, 1-(4-Metlioxy-benzyl)-1H-indole-2-carboxy[ic acid (1-isopropyl-piperidin-4-yI)- amide, (4-lsopropyiamino-piperid;n-1-yl)-[1-(4-methoxy-benzy))-1H-indo)-2-yi]-methanone, 1-(4-Trifluoro-mettioxy-benzyl)-1 H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)- amide, 1-{2-Chlcro-ben2yl)-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)- amide, 1-(2-Chloro-b6nzy()-1H-indoIe-2-carboxylic acid (3,4,5,6-tetrahydro-2H- [1,4']bipyridinyl-4-yl)-amide, 1-(2-Chloro-benzyl)-1H-indo)e-2-carboxy)ic acid (3,4,5,6-tetrahydro-2H-I1,4']bipyridinyl-4-ylmethy!)-amide, 1-(3,5-Dichloro-benzyl)-1H-indole-2-carboxylicacid (1-iscpropyi-piperidin-4-yi)-amide,.[1-{3,5-Dichloro-benzyl)-1H-indol-2-yl]~(4-isopropy(amino-piperidin-1-y[)-methanone, 3-Fiuoro-1-[5-(5-ch(oro-thiophen-2-y[)-isoxazol-3-ylmethyll-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1- [5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-cyano-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yimethyl]-3-cyano-7-methyl-1H-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, l-[2-(5-Chloro-thiophen-2-yi)-thiazot-5-ylmethyl]-1H-indoIe-2-carboxy(ic acid (1- isopropyl-piperidin-4-yl)-amide, 1-(3-Chloro-benzyl)-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-yl)-amide, [1-(3-Chloro-benzyl)-1H-indol-2-ylH4-isopropylamino-piperidin-1-yl)- methanone, 1-[2-(4-Chloro-phenyl)-ethyl]-1H-indole-2-carboxylic acid (1-tsopropyl-piperidin-4-yl)- amide, 1 -[2-(2,4-Dichloro-phenyi)-ethylJ-1 H-indole-2-carboxylic acid (1-isopropyl-piperidin-4- yl)-amide, 1-[2-(3-Methoxy-phenyl)-ethyl]-lH-indoie-2-carboxylic acid (1-isopropyt-plperidin-4-yl)- amide, 1-[2-(4-Chlcro-pheny!)-ethyl]-4-methoxy-1H-indole-2-carboxyltc acid (1-lsopropyl- piperidin-4-yl)-amide, 4-8romo-1-[5-(5-chloro-thiophen-2-yl)-iscxazol-3-y!methyl]-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-yimethy|]-4-methyl-1 H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 5-Bromo-i-[5-(5-cliloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide, 1-[&-(5-Chloro-thiophen-2-yi)-isoxazo!-3-ylmethyl]-5-cyano-1H-indo!e-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amFde, 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-trifluoromethyl-1H-indoie-2- carboxylic acid (l-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4,7-dimethyM H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yt)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethylJ-4,7-dimethoxy-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 4,7-Dichloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid {1-isopropyl-piperidin-4-yl)-amide, 5,7-Dichloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethy!]-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 4-Chlaro-1-[5-(5-chloro-thiophen-2-yl)-fSoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1 H-indole-2-carboxylic acid (4-methyl-piperazin-1-yl)-amide, [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1 H-indole-2-carbonyi}-(1- isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester, [{1 -[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl}-7-methyl-1 H-indoie-2-carbonyl}-{1- isopropyl-piperidin-4-yl)-amino]-acetic acid, 1-[5-(5-Chloro-thioplien-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbox1icacid [1-(1-ethyl-propyl)-piperidin-4-y|]-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid (1-methyl-piperidin-4-yl)-amide, 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid [1- (2,2,2-trifluoro-ethyl)-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethylj-1H-indole-2-carboxylic acid (1- formyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-y[methyl]-1H-indole-2- carboxylic acid (1- carbannoyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazoi-3-ylm ethyl]-1 H-indole-2-carboxylic acid {1- methane-sulfonyl-piperidin-4-y|)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid {1-acetyl-piperidin-4-yi)-amide, 1-[5-(5-Chloro-thicphen-2-y()-isoxazoI-3-yImethy(J-lH-indole-2-carboxylic acid [1-(2- chloro-pyrimidin-4-yl)-piperidin-4-yl]-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]'1H-indcle-2-carboxylic acid (1- pyrimidjn-4-yl-piperidin-4-yl)-amide, {1-[&-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indot-2-ylH4-(pyridin-4-yloxy)-piperidin-1-yl]-methanone, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-tndole-2-carboxylic acid [4-(1H- imidazol-4-yi)-phenyl]-amide, 1-[5-{5-Chloro-thicphen-2-yl)-isoxazol-3-ylmethyl]-1H-indoie-2-carboxylicacid (4-pyridin-3-yl-thiazol-2-yl)-amide, 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-lH-indole-2-carboxylic acid [3- (pyrrolidine-1-carbonyi)-4,5-dihydro-isoxazol-5-ylmethyll-amide, 1-[5-(5-Chloro-tiiiophen-2-yl)-isoxazol-3-ylmethyi]-1H-indole-2-carboxylic acid (1-(sob(Jtyl-piper(d(n-4-yf)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazo13-ylmethy|]-1H-indole-2-carboxylic acid (1- propyl-piperidin-4-yl)-amide, 4-({1-[5-(5-Chloro-thioplien-2-yl)-isoxazol-3-ylmethyll-1H-jndole-2-carbonyl}-amino)- piperidjne-1-carboxylic acid methyl ester, 1-[5-(5-Chloro-thicphen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (4- isopropyl-piperazin-1-yl)-amide, 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxyHc acid (4-ethyl- piperazin-1-yl)-amide, 1-[5-{5-Chloro-thiophen-2-yi)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylicacid pyridin-4-yl-(3,4,5.6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-nitro-1 H-indole-2-carboxylic acid pyridin-4-yl-(3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide. 1-[5-(5-Chloro-thiophen-2-yi)-isoxazol-3-ylmethyl]-3-cyano-1H-indole-2-carboxylicacid (3,4,5,6-tetrahydro-2H-[1,4']bipyricljnyl-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyll-3,7-diiodo-4-methoxy-1H-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yl)-annide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3,7-dicyano-4-methoxy-1H-indole-2- carboxylic acid (1-isopropyt-piperidin-4-yl)-amide, 1-[2-(4-Chloro-phenyl)-thiazol-4-ylmethyll-iH-indole-2-carboxylic acid (1-isopropyl- piperidin-4-yl)-amide, 1-{1,7-Dichloro-isQquinolin-3-ylmethyl)-1H-indole-2-carboxylic acid (1-isopropyl- piperidin-4-yl)-amide, 1-[3-(4-Chloro-phenyl)-isoxazol-5-ylmethyll-1H-indole-2-carboxylicacid (l-isopropyl-piperidin-4-yl)-amide, 1-[5-(4-Chloro-phenyl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid {1-isopropyl- piperidin-4-yl)-amtde, 1-I3-(4-Chloro-phenyl)-[1,2,4]oxadiazol-5-ylmethyl]-1H-indole-2-carboxylic acid (1- isopropyl-piperidin-4-y|)-amide, 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-methanesulfonyl-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[{4-Chloro-phenylcarbamoyl)-methyl]-5-methanesu!fonyl-1 H-indole-2-carboxylic acid (1- isopropyl-piperidin-4-y|)- amide, 5-Ghloro-1-l(5-chloro-pyridin-2-ylcarbamoyl)-mettiyll-1H-indote-2-carboxylic acid (1- isopropyl-piperidin-4-yl)-amide, 1-[(5-Chlora-pyridin-2-ylcarbamoyl)-methyll-5-fluoro-1H-indo!e-2-carboxylic acid (1- isopropyl-piperidin-4-yl)-annide, 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyll-5,7-difiuoro-1H-indole-2-carboxylic acid (1- isopropyl-piperidin-4-yl)-amide, S-1-[5-(5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1H-lnd(3le-2-carboxylic acid (1-ethyl- pyrrolidin-3-yl)-amide, R-1-t5-(5-Chloro-thiophen-2-yl)-isoxazol-3'ylmethyl]-1H-indole-2-carboxylic acid (1-ethyl- pyrrolidin-3-yl)-amide, R-1-[5-(5-Chloro-thiophen-2-yl)-isoxazcl-3-ylmethyl]-1H-indole-2-carboxylic acid (1-isopropyl-pyrrolidin-3-yl)-amide, S-1-[5-(5-Chloro-thJophen-2-yl)-isoxazol-3-ylmelhyl]-1H-indole-2-carboxyiic acid (1- iscpropyl-pyrrolidin-3-yl)-amide, I{1-t5-(5-Chloro- thiophen-2-yl)-isoxazol-3-ylmethyi]-4-trifluoromethyl-1H-indole-2-carbonyl}-(1" isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester, [{1-[5-{5-Chloro-thlophen-2-yl)-isoxazol-3-ylmethy!]-4,7-dimethyl-1H-indole-2-cart>onyl}- (1-isopropyl-piperidin-4-yl)-aminoj-acetic acid ethyl ester, [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmelhyl]-4,7-dimethoxy-1H-indole-2- carbonyl}-(1-isopropyl-piperklin-4-yl)-aminoV-acetic acid ethyl ester, [{4,7-Dichlcro-1-[5-(5-chioro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbcnyl}- {1-isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester, [{5,7-Dichloro-1-[5-(5-chloro-thiophen-2-yl)Hsoxazol-3-ylmethyl]-1H-indole-2-carbonyl}-(1-isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester, [{4-Chloro-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-y!methyll-1H-indole-2-carbonyl}-{1- isopropyl-piperidin-4-yl)-aminol-acetic acid ethyl ester, [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazcl-3-ylmethyl]-4-trlfluoromethyl-1H-indole-2- carbonyl}-(1-isopropyl-piperidin-4-yl)-amino]-acetic acid, [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4,7-dimethyl-1H-indole-2-carbonyl}- (1-isopropyl-piperidin-4-yl)-amino]-aceticacid, [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-4,7-dimethoxy-1H-indole-2-carbonyl}-(1-iscpropyl-piperidin-4-yl)-amino]-aceticacid, [{4,7-Dichloro-1-I5-(5-chloro-thioph6n-2-yl)-isoxazol-3-ylmethyll-1H-indole-2-carbonyl}- (1-isopropyl-piperidin-4-yl)-amino]-acetic acid, [{5,7-Dichloro-1-[5-(5-chlorc-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}- (1-isopropyl-piperidin-4-yl)-amino]-acetic acid, U4-Chloro-Vl5-(5-chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-lH-indole-2-carbonyl}-(1- isopropyl-piperidin-4-yl)-amino]-acetic acid, 1-[5-{5-Ch!oro-thiophen-2'yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indoie-5-carboxylic acid isopropyl ester, 1-[5-(5-Chtoro-thiophen-2-yl)-isoxazcl-3-ylmethyt]-2-(1-isopropyl-piperidin-4- ylcarbamoyl)-1H-indole-5-carboxylic acid, 1-I5-(5-Chloro-thiophen-2'yl)-isoxazol-3-ylmethyl]-5-hydroxymethyl-1H-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-{1-isopropyl-piperidln-4- ylcarbamoyl)-1H-indole-5-carboxylic acid ethyl ester, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-yl carbamoyl)- 1H-indole-5-carboxylic acid methyl ester, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethy[]-2-(1-isopropyl-piperidin-4- ylcarbamoyl)-1 H-indole-5-carboxylic acid 2,2-dimethyi-propionyloxymethyl ester, 1-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-2-(1-isopropyl-piperidln-4-ylcarbamoyl)-1H-lndole-5-carboxyllcacid isopropyl ester, 1 -[5-(5-Chloro-thiophen-2-yl)-t1.3,4]thiadiazol-2-ytmethyl]-2-{1 -isopropyl-piperidin-4- ylcarbamoyl)-1H-indole-5-carl>oxylic acid, 1-[(4-Chloro-phenylcarbamoyl)-methyl]-2-(1-isopropyi-piperidln-4-ylcarbamoyl)-1H-indole- 5-carboxylic acid isopropyl ester, 1-[(4-Chloro-phenylcarb-amoyi)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1 H-indole- 5-carboxylic acid, 1 -[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarb-amoyl)-1H-indo!e-4-carboxylic acid methyl ester, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazoi-3-ylmethyl]-2-(1-isoprDpyl-piperidin-4- ylcarbamoyl)-1H-indole-4-carboxylic acid, 1-[5-{5-Chloro-thiophen-2-yl)-isoxa2ol-3-ylmethyl]-1H-indole-2,5-dicarboxylic acid 5- amide 2-[(1-isopropyl-piperidin-4-yl)-amide], 1-[{4-chloro-pheny!carbamoyl)-methyl]-1H-indole-2-carboxylic acid (1-isopropyl- piperidin-4-yl)-amide, 1-[(5-chloro-thiophen-2-ylcarbamoyl)-methyl]-1H-indole-2-carboxylic acid (1-isopropyl- piperidin-4-yl)-amide, 1-[(4-chloro-2-fluoro-phenylcarbamoyl)-methyi]-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-tndole-2-carboxylic acid (l-isopropyl- piperidin-4-yl)-amide, 1-[(4-chloro-phenylcarb-amoyl)-methyi]-1H-indole-2-carboxylic acid (3,4,5,6-tetrahydro- 2H-[1,4']blpyridinyl'4-ylmethyl)-amide, 1-[(4-chloro-phenytcarbamoyl)-methyl]-1H-indole-2-carboxylicacid (3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-yl)-amide, N-(4-chloro-phenyl)-2-{2-t4-(pyridin-4-ylamino)-piperidine-1-carbonyl]-indol-1-yl}-acetamide, 1-[(4-chloro-phenyl-carbamoyl)-methyl]-1H-indole-2-carboxylicacid (1-cyclopropyl-piperidin-4-yl)-amide, N-(4-chloro-phenyl)-2-[2-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)Hndol-1-yl]-acetamide, 1-[{4-chloro-phenylcarbamoyl)-methyl]-5-nitro-1H-indole-2-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide, 5-amino-4-chloro-1-[5-(5-chloro-thtophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2- carboxylic acid (1-isopropyl-piperidin-4-yl)-amide, 1-[5-{5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxytic acid (1-cyanomethyl-piperidin-4-yl)-amide, 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid [1-(2- hydroxy-ethyl)-piperidin-4-yl]-amide, 1-[5-(5-ch!oro-thiophen-2-yl)-isoxazo!-3-ylmethyl]-1H-indole-2-carboxylic acid [1-(2- methoxy-ethyl)-piperidrn-4-yl]-amide, 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1- carbamoyl methyl-pi peridin-4-yl)-amide, 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1- methylcarbamoy I methyl-pi peridin-4-yl)-amide, 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid [1-(1H- imidazol-2-ylmethyl)-piperidin-4-yl]-amide, 1-[5-(5-chloro- thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid [1-(2- dimethylamino-acetyl)-piperidin-4-yl]-amide, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4- ylcarbamoyl)-1H-indole-5-carboxylic acid 1-ethoxycarbonyioxy-ethyl ester, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4- ylcarbamoyl)-1H-indole-4-cart»oxylic acid 1-ethoxycarbonyloxy-ethyl ester, 1-[5-(5-Chlcro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-tsopropyi-piperidin-4-ylcarbamoyl)-1H-rndole-4-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester, 1-[5-(5-Chloro-thio-phen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidtn-4-ylcarbamoyl)-1H-lndole-5-carboxylic acid 1-(2,2-dimethy[-prcpionyloxy)-ethyl ester, 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-4-carboxylic acid 1-(2,2-dimethyl-proplonyloxy)-ethyl ester, 1-[5-(5-Chlora-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1'isopropyl-piperidin-4-ylcarbamoyl)-1H-indoie-5-carboxylicacid5-methyl-2-oxo-[1.3]dioxol-4-ylmethyl, 1-[5-{5-Chloro-thiophen-2-yI)-isoxazoi-3-yl-methyl]-2-{1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-4-carboxylic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl. 1-[5-(5-Chloro-thiQphen-2-yl)-isoxazol-3-y(-methyl]-2-{1-isopropyl-piperidin-4-ylcarbamoyi)-1H-indole-5-carboxylicacid 1-cyclo-hexyloxy-carbonyloxy-ethyl ester or 1-[5-{5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyi]-2-(1-isopropyl-piperidin-4-ylcarbamoyi)-1 H-indole-4-carboxylic acid 1 -cyclohexyloxy-carbonyloxy-ethyl ester. 5. A process for the preparation of a compound of the formula I as claimed in one or more of claims 1 to 4, which comprises condensing a compound of the formula 14 with a HR8' formula I 15 compound of the formula HR1' to give a compound of the formula 15 and optionally converting the compound of the formula 15 into a compound of the formula I, wherein the residue R1' has the donation of-N(R'l)-R2-V-G-M as indicated in claims 1 to 4, but where in R1' functional groups can also be present in the form of groups that are subsequently transformed into the final functional groups present in -N(R'1 )-R2-V-G-M, and where the residue R1O denotes the group -Q-RO or can denote a group which is subsequently transformed into the group -Q-R1, and where the group -C(0)-R49 can be a carboxylic acid group or derivatives thereof, and where the groups R'*, R'", R11 R1" and R1"* in the formulae 14 and 16 have the corresponding definitions of R1, R1, R*, R*, and R' in formula I as defined in claims 1 to 4 or functiona} groups in them can also be present in protected form or in the form of precursor groups. A pharmaceutical preparation, comprising at least one compound of the formula I as claimed in one or more of claims 1 to 4 in all its stereoisomeric forms and mixtures thereof in any ratio and/or its physiologically tolerable salts and a pharmaceutically acceptable carrier. A compound of the formula I R6 R7 R'—V G M (I) in all its stereoisomeric forms and mixtures thereof in any ratio and/or their physiologically tolerable salts for use in inhibition of factor Xa and/or factor Vila or for influencing blood coagulation or fibrinolysis, wherein R°is 1. a monocyclic or bicyciic 6- to 14-inembered aryl, wherein aryl is mono-, di- or trisubstituted Independently of one another by R®, 2. a monocyclic or bicyciic 6- to 14-membered heteroaryl out of the group pyridyl, pyrimidinyl, indolyl, isoindolyl, indazoiyl, phthalazinyl, quinolyl, isoquinolyl, benzothiophen, quinazDJiny! and phenylpyridyl, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R1, or 3. a monocyclic or bicyciic 5- to 14-membered heteroaryl, containing one, two, three or four heteroafoms chosen from nitrogen, sulfur or oxygen, wherein said heteroaryl is unsubstituted or mono-, di- or trisubstituted |
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1102-chenp-2004 abstract-duplicate.pdf
1102-chenp-2004 claims-duplicate.pdf
1102-chenp-2004 correspondence-others.pdf
1102-chenp-2004 correspondence-po.pdf
1102-chenp-2004 description (complete)-1.pdf
1102-chenp-2004 description (complete)-2.pdf
1102-chenp-2004 description (complete)-duplicate-1.pdf
1102-chenp-2004 description (complete)-duplicate-2.pdf
1102-chenp-2004 description (complete)-duplicate.pdf
1102-chenp-2004 description (complete).pdf
1102-chenp-2004 pct search report.pdf
| Patent Number | 226359 | |||||||||||||||||||||
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| Indian Patent Application Number | 1102/CHENP/2004 | |||||||||||||||||||||
| PG Journal Number | 02/2009 | |||||||||||||||||||||
| Publication Date | 09-Jan-2009 | |||||||||||||||||||||
| Grant Date | 17-Dec-2008 | |||||||||||||||||||||
| Date of Filing | 18-May-2004 | |||||||||||||||||||||
| Name of Patentee | SANOFI-AVENTIS DEUTSCHLAND GmbH | |||||||||||||||||||||
| Applicant Address | BRUNINGSTRASSE 50, D-65926 FRANKURT AM MAIN | |||||||||||||||||||||
Inventors:
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| PCT International Classification Number | CP7D413/14 | |||||||||||||||||||||
| PCT International Application Number | PCT/EP02/12500 | |||||||||||||||||||||
| PCT International Filing date | 2002-11-08 | |||||||||||||||||||||
PCT Conventions:
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