Title of Invention	NOVEL PYRROLIDINE-3,4-DICARBOXAMIDE DERIVATIVES
Abstract	The invention is concerned with novel pyrrolidine-3,4-dicarboxamide derivatives of Formula (I) ; wherein R1 to R9 and X are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the coagulation factor Xa and can be used as medicaments.

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Novel pyrroIidiDe-3,4"dicarboxamide derivatives The invention is concerned with novel pyrroKdme-3>4-dicarboxamide derivatives of the formula (I) wherein X is N or C-R6; R1 is hydrogen, lower-alkyl, cycloalkyl> cydoalkyHower-alkyl, fhioro-lower-alkyl> hydroxy-lower-alkyl, CN-lower-alkyl, hydroxy substituted fluoro-lower-alkyl, lower-alkinyl, R10C(O)-, R10OC(O)-, N(R11,R12)C(O)-> R10OC(O)-lower-al3cyl3 N(Ra>R12)C(O)4ower-alkyl, R10-SO2, R10-SO2-lower-alkyl, NCR11^12)^©,, N(Ru,R12)-SO2-lower-alkyl? aryi-lower-alkyi, heteroaryl, heteroaryi-lower-alkyl, lower alkoxy-lower aDq^i, lower alkoxycarbonyl-cycloalk)d-lower aBcyl or heteroq^clyl-lower alkyl; R is hydrogen or lower-alkyl; R is aryl, aryl-lower-alkyl, heteroar}d or heteroaryl-lower-alkyl; R4 is hydrogen, lower-alkyl or hydroxy; R53 R55 R7 and R8 independently from each other are selected from the group consisting of hydrogen^ halogen, lower-alkyl, lower-alkoxy, fiuoro-lower-alkyl, fluoro-lower-alkyloxy or CN; R9 is aryl, heterocyclyl, heteroaryl or heterocyclyl-C(O)-; R is hydrogen, lower-allcyl, cydoalkyl, cydoalkyl-lower-alkyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-arkyl-SO2-lower-alkyl, aryl, aryl-lower-alkyl, heteroaryl/heteroaryl-lower-alkyl or heterocydyl; R and R independently from eadi other are sdected from the group consisting of hydrogen, lower-allcyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, cydoalkyi, cydoalkyl-lower-alkyl, aryl, aryl-lower-alkyl, heteroaryl and heteroaryl-lower-alkyl; or Ru and R12, together with the nitrogen atom to whidi they are attached, form a heterocydic ring selected from the group consisting of piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl, pyrrolinyl or azetidinyl, which heterocydic ring can optionally be substituted with lower-alkyl, halogen or hydroxy; and pharrnaceutically acceptable salts thereof. Further, the invention is concerned with a process for the manufacture of the above compounds, pharmaceutical preparations which contain such compounds as well as the use of these compounds for the production of pharmaceutical preparations. The compounds of formula (I) are active compounds and inhibit the coagulation factor Xa. These compounds consequently influence blood coagulation. They therefore inhibit the formation of thrombi and can be used for the treatment and/or prevention of thrombotic disorders, such as amongst others, arterial and venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease (PAOD), unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke (cerebral thrombosis) due to atrial fibrillation, inflammation and arteriosclerosis. They have potentially benefit in the treatment of acute vessel closure associated with thrombolytic therapy and restenosis, e.g. after transluminal coronary angioplasty (PTCA) or bypass grafting of the coronary or peripheral arteries and in the maintenance of vascular access patency in long term hemodialysis patients. F.Xa inhibitors of this invention may form part of a combination therapy with an anticoagulant with a different mode of action or with a platelet aggregation inhibitor or with a thrombolytic agent. Furthermore, these compounds have an effect on tumour cells and prevent metastases. They can therefore also be used as antitumour agents. Other inhibitors of factor Xa, which are not structurally related to the compounds of the present invention, had previously been suggested for the inhibition of the formation of thrombi and for the treatment of related diseases (WO 03/045912). However, there is still a need for novel factor Xa inhibitors which exhibit improved pharmacological properties, e.g. an improved selectivity towards coagulation factor Xa. The present invention provides the novel compounds of formula (I) which are factor Xa inhibitors The compounds of the present invention unexpectedly inhibit coagulation factor Xa and also exhibit unproved pharmacological properties compared to other compounds already known in the art. Unless otherwise indicated, the following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein. In this specification the term "lower" is used to mean a group consisting of one to seven, preferably of one to four carbon atom(s). The term £Chalogen" refers to fluorine, chlorine, bromine and iodine, with fluorine, chlorine and bromine being preferred. The term "alky!", alone or in combination with other groups, refers to a branched or straight-chain monovalent saturated aliphatic hydrocarbon radical of one to twenty carbon atoms> preferably one to sixteen carbon atoms, more preferably one to ten carbon atoms. Lower-alkyl groups as described below also are preferred alkyl groups. The term "lower- alkyPj alone or in combination with other groups, refers to a branched or straight-chain monovalent alkyl radical of one to seven carbon atoms, preferably one to four carbon atoms. This term is further exemplified by such radicals as methyl, ethyl, n-propyl, isopropyl, n-butyl, i-butyl, t-butyl. Lower-alkyl groups can optionally be substituted, e.g, by hydroxy or CN. Such substituted lower-alkyl-groups are referred to as "hydroxy-lower-alkyl" or "CN-lower-alkyl" respectively. Other possible optional substituents are e.g. halogen. Unsubstituted lower-alkyl groups are preferred. The term "fluoro-lower-alkyl" refers to lower-allcyl groups which are mono-or multiply substituted with fluorine. Examples of fluoro-lower-alkyl groups are e.g. CFH2, CF2H3 CF3, CF3CH2, CF3(CH2)2, (CF3)2CH and CF2H-CF2. The term "cycloalkyT refers to a monovalent carbocyclic radical of 3 to 10 carbon atoms, preferably 3 to 6 carbon atoms, such as cyclopropyl, cydobutyl, cyclopentyl, or cydohexyl. The term "alkoxy" refers to the group R3-O-> wherein RJ is an alkyi. The term 'lower-alkoxy* refers to the group R'-O-, wherein R' is a lower-aBcyL The term "thio-alkoxy" refers to the group R'-S-, wherein R' is an alkyl. The term "thio-lower-alkoxy" refers to the group R'-S-, wherein R* is a lower-alkyL The term "fluoro-lower-alkoxy" refers to the group R"-O-, wherein R" is fluoro-lower-alkyl. Examples of fluoro-lower-alkoxy groups are e.g. CFH2-O, CF2H-O, CF3-O, CF3CH2-O, CF3(CH2)2-O, (CF3)2CH-O, and CF2H-CF2-O. The term "alkenyT, alone or in combination with other groups, stands for a straight-chain or branched hydrocarbon residue comprising an olefinic bond and 2 to 20, preferably 2 to 16 carbon atoms, more preferably 2 to 10 carbon atoms. Lower-alkenyl groups as described below also are preferred alkenyl groups. The term 'lower-alkenyT refers to a straight-chain or branched hydrocarbon residue comprising an olefinic bond and 2 to 7, preferably 2 to 4 carbon atoms, such as e.g. 2-propenyL The term "alkinyl", alone or in combination with other groups, stands for a straight-chain or branched hydrocarbon residue comprising a tripple bond and up to 20, preferably up to 16 carbon atoms. The term "lower-alkinyl" refers to a straight-chain or branched hydrocarbon residue comprising a tripple bond and 2 to 7, preferably 2 to 4 carbon atoms, such as e.g. 2-propinyl. Lower-alkinyl groups can be substitutedj e.g. by hydroxy. The term "alkylene" refers to a straight chain or branched divalent saturated aliphatic hydrocarbon group of 1 to 20 carbon atoms, preferably 1 to 16 carbon atoms, more preferably up to 10 carbon atoms. Lower-alkylene groups as described below also are preferred alkylene groups. The term "lower-alkylene" refers to a straight chain or branched divalent saturated aliphatic hydrocarbon group of 1 to 7, preferably i to 6 or 3 to 6 carbon atoms. Straight chain alkylene or lower-allryiene groups are preferred. The term "aryl" relates to the phenyl or naphthyl group> preferably the phenyl group, which can optionally be substituted by 1 to 5 , preferably 1 to 3, substituents independently selected from the group consisting of lower-alkenyl, lower-alkinyl, dioxo-lower-alkylene (forming e.g. a benzodioxyl group), halogen, hydroxy, CN, CF3, NH2, N(H, lower-alkyl), N(lower-alkyl)2, aminocarbonyl, carboxy, NO2, lower-alkoxy, thio-lower-alkoxy, lower-alkylsufonyl, aminosulfonyl, lower-alkylcarbonyl, lower-alkylcarbonyloxy, lower-alkoxycarbonyl, lower-alkyl-carbonyl-NH, fluoro-lower-alkyl, fluoro-lower-alkoxy, lower-alkoxy-carbonyl-lower-alkoxy, cafboxy-lower-alkoxy, carbamoyl-lower-alkoxy, hydroxy-lower-alkoxy, NH2-lower-alkoxy, N(H, lower-alky^-lower-alkoxy, N (lower-alkyl)2-lower' alkoxy, benzyloxy-lower-alkoxy, mono- or di-lower alkyl substituted amino-sulfonyl and lower-alkyl which can optionally be substituted with halogen, hydroxy, NH2> N(H, lower-alkyl) or N(lower-alkyl)2? preferably selected from the group consisting of lower-alkenyi, lower-alkinyl, dioxo-lower-alkylene (forming e.g. a benzodioxyl group), halogen, hydroxy, CN, CF3> NH2, N(H> lower-alkyl), N(lower-alkyl)2> aminocarbonyl, carboxy, NO2> lower-alkoxy, thio-loM^er-alkoxy, lower-alkylsufonyl, aminosulfonyl, lower-alkylcarbonyl, lower-alkylcarbonyloxy, lower-alkoxycarbonyl, lower-alkyl-cafbonyl-NH5 fluoro-lower-alkyl, fluoro-lower-alkoxy, lower-alkoxy-carbonyl-lower-alkoxy, carboxy-lower-alkoxy, carbamoyl-lower-alkoxy, hydroxy-lower-alkoxy, NH2-lower-a]koxy, N(H, lower-alkyl)-lower-alkoxy, N(lower-alkyl)2-lower-alkoxy, benzyloxy-lower-alkoxy and, lower-alkyl which can optionally be substituted with halogen, hydroxy, NH2> N(H, lower-alkyl) or N(lower-alkyl)2.. Preferred substituents are halogen, lower-alkoxy, fluoro-lower-alkoxy, thio-lower-alkoxy, and amino. The term "heterocydyT as used herein denotes non-aromatic monocyclic heterocycles with 4 or 6 ring members, which comprise 1, 2 or 3 hetero atoms selected from nitrogen, oxygen and sulfur. A hetero atom can be -SO- or -SO2-. Examples of suitable heterocycles are pyrrolidinyl, oxopyrrolidinyl, isoxazolidinyl, isoxazolinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, 2-oxo-piperidinyl, 3-oxo-morpholinyl, 2-oxo-piperazinyl, 2-oxo-oxazolidinyl, 2-oxo-azetidinyl, piperazinyl, morpholinyl, pyranyl, tetrahydrop'jTranyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-thiazolyl. Preferred heterocydes are, morpholinyl, 3-oxo-morpholinyl, 2-oxo-piperazinyl and 2-oxo-piperidinyl. A heterocyclyl group may have a substitution pattern as described earlier in connection with the term "aryl". One or two ring member carbon atoms of a heterocyclyl group maybe replaced with a carbonyl group. The term "heteroaryl" refers to an aromatic 5 to 6 membered monocyclic ring or 9 to 10 membered bicyclic ring which can comprise 1,2, 3 or 4> preferably 1, 2 or 3 atoms selected from nitrogen, oxygen and/or sulphur, such as foryl, pyridyl, pyridazinyl, oxo-pyridazinyl, pyrimidinyl, 2-oxo-pyridinyl, 2-oxo-pyrimidinyl pyrazinyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1,2,3-thiadiazolyl, benzoimidazolyl, indolyl, indazolyl, Preferred heteroaryl groups are 2-oxo-pyridinyL, 2-oxo-pyrimidinyl, pyridinyl, and indolyl. A heteroaryl group may have a substitution pattern as described earlier in connection with the term "aryT. Preferred substituents are halogen, lower-alkyl, lower-alkoxy or CN. One or two ring member carbon atoms of a heteroaryl group maybe replaced with a carbonyl group. The term "mono-lower alkyl substituted amino" and "di-lower alkyl substituted amino* refer to -NHR and -NRR5 respectively, wherein R and RJ independent from each other are lower alkyl. Preferred radicals for the chemical groups whose definitions are given above axe those specifically exemplified in Examples. Compounds of formula (I) can form pharmaceutically acceptable acid addition salts. Examples of such pharmaceutically acceptable salts are salts of compounds of formula (I) with physiologically compatible mineral acids, such as hydrochloric add, sulphuric add, sulphurous add or phosphoric add; or with organic adds, such as methanesulphonic acid, p-toluenesulphonic add, acetic add, lactic add, trifluoroacetic add, citric acid, fumaric acid, maleic acid, tartaric add, succinic add or salicylic add. The term "pharmaceutically acceptable salts" refers to such salts. Compounds of formula (I) in which a COOH group is present can further form salts with bases. Examples of such salts are alkaline, earth-alkaline and ammonium salts such as e.g. Na-, K-, Ca- and Trimethylammoniumsalt The term "pharmaceutically acceptable salts" also refers to such salts. Acid addition salts as described above are preferred. In detail, the present invention relates to compounds of formula (I) X is N or C-R6; R1 is hydrogen, lower-alkyl, cycloalkyl, cycloalkyl-lower-alkyl, fluoro-lower-alkyl, hydroxy-lower-alkyl, CN-lower-alkyl, hydroxy substituted fluoro-lower-alkyl, lower-alkinyl, R10C(O)-, R10OC(O)-, N(Rn,R12)C(O)-, R10OC(OHower-alkyl, N(Ru,R12)C(OHower-aIkyl, R10-SO2, R20-SO2-lower-alkyl, N(R11 J112)-SO2, N(R11 Jl12)-SO2-lower.alkyi, aryl-lower-alkyl, heteroaryi, heteroaryl-lower-alkyl, lower alkoxy-lower alkyl, lower alkoxycarbonyi-q^cloalkyl-lower alkyi or keterocyclyl-lower alkyl; R is hydrogen or lower-alkyl; R is arylj aryl-lower-allcyl, heteroar^'i or heteroaryi-lower-alkyl; R4 is hydrogen, lower-alkyl or hydroxy; R5> R6, R7 and R8 independently from each other are selected from the group consisting of hydrogen, halogen, lower-alkyl, lower-alkoxy, fluoro-lower-alkyl, fluoro-lower-alkyloxy or CN; R9 is arjd, heterocyclyl, heteroaryl or heterocyclyl-C(O)-; R10 is hydrogen, lower-alkyl, cycloalkyl, cycloalkyl-lower-alkyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkyl-SO2-lower-alkyl, aryl, aryl-lower-alkyl, heteroaryl, heteroaryl-lower-alkyl or heterocydyl; Ru and R12 independently from each other are selected from the group consisting of hydrogen, lower-alkyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, cycloalkyl, q^cloalkyl-lower-alkyl, aryl, aryl-lower-alkyl, heteroaryl and heteroaryl-lower-alkyl; or R and R , together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from the group consisting of piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl, pyrrolinyl or azetidinyl, -which heterocyclic ring can optionally be substituted "with lower-alkyl, halogen or hydroxy, and pharmaceuticafly acceptable salts thereof Preferably R1 is hydrogen, lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, fluoro-lower alkyl, hydroxy-lower alkyl, CN-lower alkyl, hydroxy substituted fluoro-lower alkyl, lower alkinyl, R10C(O)-, R10OC(O)^ N(Rn,R12)C(O)-, R10OC(O)-lower alkyl, N(Rn,R12)C(O)-lower alkyl, R10-SO2, R10-SO2-lower alkyl, N(RU5R12)-SO2? N(Rn,R12)-SO2-lower alkyl, ar)i-lower alkyl, heteroaryl or heteroaryl-lower alkyl; R10 is hydrogen, lower alkyl, cydoalkyl, q^doalkyl-lower alkyl, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkyl-SO2-lower alkyl, aryl, aryl-lower alkyl, heteroaryl or heteroaryl-lower alkyl. Compounds of formula (I) are individually preferred and physiologically acceptable salts thereof are individually preferred, with the compounds of formula . (I) being particularly preferred. The compounds of formula (I) have at least two asymmetric C atoms and can therefore exist as an enantiomeric mixture, diastereomeric mixture or as optically pure compounds. Preferred are compounds which are 3R,4R-pyrrolidine-3,4-dicarboxylic acid derivatives. One preferred embodiment of the present invention therefore relates to compounds of formula (I) as defined above, characterised by formula (la) wherein R1, R2, R3, R4, R5> R7, R8, R9 and X are as defined above, and pharmaceutically acceptable salts thereof. Preferred compounds of formula (I) are those, wherein R1 is hydrogen, lower-alkyl, fluoro-lower-alkyl, hydroxy-lower-alkyl, CN-lower-alkyi, HC(O)~, lower-aUcyl-CXO)-, lower-allcoxy-C(O)-? lower-alkoxy-C(O)-lower-aIkyI, NH2-C(O)-lower-alkyl, lower-aIkyl-NH-C(O)-lower-alkyl, NH2-SO2, lower-alkyl-SO2, fluoro-lower-aIkyl-SO2, N(lower-alkyl)2-SO2 or pyrrolidino-C(O)-. Compounds as defined above, wherein R1 is lower-alkyl, fluoro-lower-alkyl, lower-alkyl-SO2) fluoro-lower-alkyl-SO2, N(lower-alkyl)2-SO2, lower-alkoxy-C(O)- or HC(O)-, are more preferred, with those compounds as defined above, wherein R1 is 2,2-difluoro-ethyl, ethanesulfonyl, methanesulfonyl, propylsulfonyl, isopropylsulfonyl, 2,2,2-trifluoro-ethylsulfonyl, isopropyl, N(CH3)2-SO2) ethoxy-carbonyl, or formyl, being particularly preferred. In another preferred embodiment of the present invention, R is hydrogen. Furthermore, compounds as defined above, wherein R is phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, NH2, lower-alkoxy and fluoro-lower-alkoxy, or R is benzyl optionally substituted with halogen, or R is pyridinyl optionally substituted with halogen, or R is indolyl, are preferred. Particularly preferred are those compounds, wherein R is phenyl substituted with halogen or R3 is pyridinyl substituted with halogen. Most preferably, R3 is 4-dbloro-phenyl or 5-chloro-pyridin-2-yl. In a further preferred embodiment of the present invention, R4 is hydrogen. Another preferred embodiment of the present invention relates to compounds of formula (I) as defined above, wherein X is C-R6 and R6 is as defined above. Preferably, X is C-R6 and R5, R6, R7 and R8 independently from each other are selected from the group consisting of hydrogen and halogen. More preferably, X is C-R6, R6 is halogen, R5, R7 and R8 are hydrogen. Most preferably, X is C-R6, R6 is fluorine, R5, R7 and R8 are hydrogen. The invention especially embraces compounds of formula (I) as described above, wherein R9 is aryl, heterocyclyl or heteroaryl. Those compounds, wherein R9 is heteroaryl, are preferred. A preferred heteroaryl group for R9 is one selected from the group consisting of furyl, pyridyl, pyridazinyl, oxo-pyridazinyl, pyrimidinyl, 2-oxo-pyridinyl, 2-oxo-pyrimidinyl pyrazinyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1,2,3-thiadiazolyl, benzoimidazolyl, indolyl and indazolyl. 2-oxo-2H-pyridin-1-yl is particularly preferred. In particular, preferred compounds are the compounds of formula (I) described in the examples as individual compounds as well as pharmaceutically acceptable salts thereof. Preferred compounds of formula (I) are those selected from the group consisting of (3R,4R)-l-(2,2>2-Trifluoro-ethyl)-pyrroHdine-3>4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H«pyridin-l-yl)-phenyl]-ainide}, (3R>4R)-l-(2>2-Difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H»pyridin-l-yl)-phenyl]-amide}, (3R>4R)-l-Sulfamoyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-p37ridin-l-yl)-phenyl] -amide}, (3R,4R)-l-Sulfamoyl-pyrrolidine-3>4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)Tridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Eiianesulfonyl-pyrroHdiiie-3,4-dicarboxylicadd3-[(4-cUoro-^^ amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R,4R)-l-Methanesiilfonyl-pyrrolidine-3,4--dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Isopropyl-pyrroUdine-3,4-dicarboxylicacid3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R>4R)-l-Methanesulfonyl-p')?rrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-p)T:rolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p}rridin-l-yl)-phenyl]-amide}, (3R,4R)-1-Meikylcarbamoylmetk^ add 3-[(4-chloro phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)7ridin-l-yl)*phenyl]-amide}, (31MI0-3-(4-Chloro-phenylca^ phenylcarbamoylj-pyrrolidine-l-cafboxj^lic acid methyl ester, (3R?4R)-l-(2-Hydroxy-ethyl)-pyrrolidine-334-dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H"pyridin-l-yl)-phenyl]-amide}, 1rans-(3RSJ4RS)"l-MethanesulfonyI-pyiToHdine-3)4-dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluorO"4-(2-oxo-2H-pyridin-l-yI)-phenyl]-amide}> (3RJ4R)-l-Met±ianesulfonyl-pyrroHdine-3?4-dicarbox)7iic add 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(3-methox7-2-oxo-2H'pyridin-l-yl)-phenyl] -airu.de}> (3R)4R)-l-Acetyi-pyrrolidine-3,4-dicarboxyiic add 3-[(4-chloro-phenyl)-amide] 4-{[4-(3-methoxy-2-oxo-2H-pyridin-I-yI)-phenyI]-amide}> tTajis-(3RS>4RS)-I-Cyanomethyl-p)Trolidine-3>4-dicarbox7iic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yi)-phenyI]-amide}, txaxis-(3RS4RS)-l-Carbamoyimethyl-p}7rrolidine-3>4"dicarboxylic add 3-[(4-chloro-phenyi)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin*-l-yl)*phenyl]-amide}, trans-CSRS^Sj-l-CS^jS-Trifluoro-propy^-p^olidine-S^-dicarboxyiic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluora-4-(2-oxo-2H-pyridin-l-yl}-p3ienyl]-amide}, (3R)4R)-l-Formyl-pyrrolidine-3,4-dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R>4R)-l-Methanesulfonyl-pyrroUdine-3)4-dicarboxylic add 3-[(4-cbloro-3-fiuoro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)Tidin-l-yl)-phenyl]-amide}} (3R)4R)-l-Meiiianesiilfonyl-pyrroIidine-3J4-dicarboxylLC add 3-[(4-chloro-2-fluoro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p}T:idin-l-yl)-plienyl]-amide}? trans-(3RS,4RS)-{3-(4-Chloro-phenylcarbamoyI)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyi]-p)7rrolidin-l-yl}-acetic add ethyl ester, (3R,4R)-l-Methanesulfon}i-pyrroKdine-3)4-dicarboxylic add 3-[(3-fluoro-4-methoxy-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyi]-ainide}s (3R,4R)-l-Methanesulfonyl-p)7rrolidine-3>4-dicarboxylic add 3-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} 4-[(lH-indol-5-yl)-amide], (3R,4R)-l-Methanesulfonyl-p)7rrolidine-3>4-dicarboxylic add 3-[(2-amino-4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-pyrroHdine-3s4-dicarboxylic add 3-{[2-fluoro-4-(2-oxo-2H-pyridin-1 -yl) -phenyi] - amide} 4- [ (4-methoxy-phenyl) - amide], (3R,4R)-I-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic add 3-[(4-chloro-phenyl)"amide] 4-[(3-fluoro-4-morpholin-4-yl-phenyl)-amide], (3S4S)-l-Methanesidfonyl-pyrrolidine-3>4-dicarbox7lic acid 3-[ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-plienyl]-amide}) (3R,4R)-l-Methanesulfonyl-p-5TTolidine-3>4-dicarboxylic acid 3-[(3-chloro-4-metitioxy-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyi]-ainide}5 (SR^^-l-Metiianesulfonyl-pyrroHdine-S^-dicarboxylic acid 3-[(4-chloro-phenyl)-methyl-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yi)-phenyl]-ainide}, (3R54R)-l-Methanesulfonyl-pyrrolidiiie-354-dicarboxylic acid 3-{ [2-fluoro-4-(2-oxo-2H-pyridin-1 -yl)-phenyl] -amide} 4- [(IH-indazol-5-yl)-amide], (3R>4R)"l-Methanesulfonyl-pyrrolidine-3>4--dicarbox5rlic acid 3-[(4-chloro-phenyl)-amide] 4-[(3-fluoro-4-[ 1,2,4]triazol-1 -yl-phenyl)-hydroxy-amide] 5 (3R>4R)-l-Methanesulfonyi-pyrrolidine-3?4-dicarboxylic add 3-[(4-chloro phenyl)-amide] 4-{[3-fluoro-4-(2-metiiyl-iiiiidazol-l-yl)-phenyl]-amide}> (3R,4R)-Pyrrolidine-3J4-dicarboxylic acid3-[(4-chloro-phenyi)-amide] 4-[(3-fluoro-2'-methylsulfanyl-biphenyl-4-yl)-amide], (3R>4R)-l-Methanesulfonyl-p)T:roHdine-3)4-dicarboxylic add 3-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} 4-[(4-methoxy-phenyl)-methyl-amide], (3R>4R)-l*Meiiaiiesulfoii)d-pyrrolidine-3)4-dicarboxylic add 3-(4-chloro-benzyiamide) 4-{[2-fluoro-4-(2-oxo-2H-p)oidiii-l-yi)-phenyl]-amide}, (3R,4R)-l-Metianesulfonyl-pyrrolidine-3,4-dicarboxyiic add 3-{[2-fluoro-4-(2-oxo-2H-p)Tidin-l-yl)-phenyl]-amide} 4-[(4-trifluoromethoxy-phenyl)-amide], (3R,4R)-l-(Propane-2-sulfonyl)-pyrroHdine-3,4-dicarboxylicadd3-[(4-diloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R,4R)-l-(2,2>2-Trifluoro-eiiianesulfonyl)-pyrroKdine-3,4--dicarbox)4icadd3-[(4-chloro-phenyl)-amidej 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yI)-phenyl]-amide}, (3R,4R)-l-Dimettylsulfamoyl-pyrrolidiae-3)4-dicarboxjdic acid 3-[(4-chloro-phen}d)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-3-(4-CHoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidine-l-carboxylic acid ethyl ester, (3R,4R)-3-(4-CKloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yI)-phenylcarbamoyl]-pyrrolidine-l-carbox}dic acid propyl ester, (3R,4R)-l-(Pyrrolidine-l-carbonyl)-pyrrolidine-3)4-dicarboxylic acid 3-[(4-chloro-phen"yi)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin- l-yl)-phenyl] -amide}, (3R,4R)- l-Metlianesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2)6-difluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}3 (3R,4R)-l-Meiiiaiiesulfoiiyl-p)7rrolidine-3>4-dicarboxylic add 3-[(4-chloro-phenyi)-amide] 4-{[2-fluoro-4-(6-oxo-6H-pyridazin-l-yl)-phenyl]-amide}> (3R,4R)-l-Methanesulfonyi-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro- phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-piperidin-l-7l)-phenyl]-amide}) (3R,4R)-l-Propanesulfonyl-pyrrolidine-3,4-dicarboxyiic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyI]-amide}, and (3R54R)-l-(2-Huoro-etiiyl)-pyrroHdine-3>4-dicarboxylic acid 3-[(4-chloro-phenyi)-amide] 4-{ [2-£luoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R54R)-Pyrrolidine-3J4"dicaxboX57iic add 3-[(4-chloro-phenyl)-ainide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yI)-phenyi]-amide}3 (3RJ4R)-3-(4-CHoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidine-l-carbosy]ic acid tert-butyl ester, (3R,4R)-Pyrrolidine-3,4-dicarboxyiic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4- (2-oxo-2H-pyridin-1 -yl)-phenyl] -amide}, (3 S,4S)-1-MetkanesiiLfonyl-pyrro^ amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R?4R)-l-Methanesulfonyi-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [4-(2?5-dihydro-p"5T:role-l-carbonyl)-phenyl]-amide}, (3R,4R)-l-Me1±Lanesulfonyi-pyrrolidine-334-dicarbo3qiic acid 3-[(4-chloro-phen"jd)-amide] 4-{[3-(morpholine«4-sulfonyl)-phenyl]-ainide}, (3R>4R)-l-Methanesulfonyi-pyrroHdine-3>4-dicarbox7^^ acid 3-[(4-chloro-phenyl)-ainide] 4-{[3-(4-methyl-pipera2ine-l-sulfonyi)-phenyl]-amide}, (3R,4R)-l-Metiianesulfonyl-pyrroUdine-3>4-dicarboxyiic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(morph.oline-4-carbonyl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-pyrrolidine-334-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(4-metiiyl-piperazine-l-carbonyl)-phenyl]-amide}; (3R,4R)-l-Methanesulfonyl-p)Trolidine-3?4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [4-(tliiomorpholine-4-carbonyl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-pyrroHdine-3?4-dicarbox5dicacid3-[(4-chloro-phenyi)-amide] 4-{ [4-(4-ethyi-piperazine-l-carbonyl)-phenyl] -amide}, (3R,4R)-l-Me1iianesulfonyl-pyrrolidiiie-3>4-dicarboxyiic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(4,4-difluoro-piperidine-l-carbonyl)-phenyl]-amide}, (3R,4R)-l-Meiiianesulfonyl-pyrrolidine-3)4-dicarbox)^lic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(4-fluoro-piperidine-l-carbonyl)-phenyl]-amide}, (3R,4R)-l-Metiianesulfonyl-pyrroHdine-3>4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(l-ox7-pyridin-2-yl)-phenyl]-amide}, (3R,4R)-l-(2)2-Difluoroethyl)-pyrrolidine-3,4-dicarbox7lic acid 3- [(5-chloro-pyridiB-2-yl)-amide] 4*{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Isopropyl-pyrroUdine-3)4-dicarbox7Kcacid3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} and pharmaceutically acceptable salts thereof. Particularly preferred compounds of formula (I) are those selected from the group consisting of (3R)4R)-l-(2>2-Difluoro-ethyl)-p)rrrolidine-3>4-dicarbox7Kc acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R»4R)-l-Eihaxiesulfonyl-pyrrolidine-334-dicarboxylic acid 3-[(4-chloro-phenyI)-amide] 4-{[2»fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-ainide}J (3R54R)-l-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R) -1 -Isopropyl-pyrrolidine-3?4-dicarboxylic acid 3- [ (4-chloro-phenyl) -amide] 4'{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyI]-amide}> (3R)4R)-l-Methanesulfonyl-pyrrolidine-3>4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2"fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}5 (3R,4R) -1 -Formyl-pyrroIidine-S^-dicarboxylic acid 3- [ (4-chloro-phenyl) -amide] 4-{ [2-fluoro-4-(2'Oxo-2H-pyridin-1 -yl)~phenyl] -amide}, (3R,4R)-l-(Propane-2-sulfonyl)-p}nTolidine-3>4-dicarboxylicacid3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)TidiQ-l-yl)-phenyl]-amide}, (3R,4R)-l-(272)2-Trifiuoro-ethanestdfonyl)-pyrroHdine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R?4R)-l-Dime1i)4sulfamoyl-pyrrolidine-3)4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R,4R)-3-(4-Chloro-phenylcarbamoyl)-4-[2-fluoro-4'(2-oxo-2H-pyridin-l-yl)-phenylcarbamoylj-p'jTTolidine-l-carboxylic acid ethyl ester, and (3R,4R)-l-Propanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R)4R)-l-(2>2-Difluoroethyl)-pyrrolidine-3,4-dicarbox5rlic acid 3-[(5-chloro-p")T:idin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Isopropyl-pyrroHdine-3,4-dicarbox5rUcacid3-[(5-cUoro-pyridin-2--yI)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} and pharmaceutically acceptable salts thereof. It will be appreciated that the compounds of general formula (I) in this invention may be derivatised at functional groups to provide derivatives which are capable of conversion back to the parent compound in vivo. The invention further relates to a process for the manufacture of compounds of formula (I) as defined above, which process comprises a) reacting a compound of formula (II) with a compound LG-R\ or b) reacting a compound of formula (III) with a compound NHRR or c) reacting a compound of formula (IV) with a compound of formula (V) wherein R1, R2, R3, R4, R5, R7, R8, R9, and X have the significances given above and LG is a leaving group. The reaction of a compound of formula (II) with a compound LG-R1 is conveniently carried out in a solvent such as e.g. dichloromethane, THF, acetonitrile, DMF, DMA, DMSO, NMP etc. with bases like DIEA, triethylamine, pyridine, N-methylmorpholine, Na2CO3> K2CO3, CS2CO3 etc. Suitable leaving groups are well known in the art, e.g. halogenides, triflates, para-nitrophenolates or -mesylates. Suitable reaction conditions for the reaction of a compound of formula (IE) with, a compound NHR R or of a compound of formula (IV) "with a compound of formula (V) are well known to the person skilled in the art Such reactions can be carried out in a solvent such as e.g. dichloromethane, DMF, acetonitrile, THF> NMP, DMA, etc. and in the presence of an activating amide coupling reagent like EDC, DIC, DCQ GDI, TBTU, HBTUrEEDQ, CIP, HOBt, HATU, PyBOP, PyBrOP, BOP, BOP-C1, TFFH, isobutylcarbamoyl chloride, etc. at a suitable temperature, which can e.g. be chosen in the range of -10°C - 120°C. Moreover, the invention further relates to another process for the manufacture of compounds of formula (I) as defined above, which process comprises d) Reacting a compound of formula (VI) or (VTII) with a compound of formula (Vll)or (V), respectively: wherein R1, R2, R3> R4, R5, R7, R8, R9, and X have the significances given above, LG is a leaving group and R is lower alkyl, cycloalkyl or cycloalkyl-lower alkyL Suitable reaction conditions for the reaction of a compound of formula (VI) with, a compound NHR R are well known to the person skilled in the art. Such reactions can be carried out in a solvent such as e.g. DMF, acetonitrile, THF, toluene, heptane, and in the'presence of a strong base like trialkyl alumina, NaH, LiHMDS, KHMDS at a suitable temperature, which can e.g. be chosen in the range of-10°C-120°C. In all general reaction descriptions the saponification process can be also avoided. Reactions from the ester to the corresponding amides are also possible in each reaction sequence 2c) throughout 2f). General synthetic processes. 1. Synthesis of pym>Bdine-3,4-dicarboxylic acid scaffolds: General Procedure: An N-protected glycine derivative such as e.g. N-benzyl glycine is condensed with a source for formaldehyde like paraformaldehyde in a suitable solvent like benzene, toluene, xylene, DMF> DMA, DMSO or acetonitrile at elevated temperatures between 60-150 °C to the corresponding azomethine ylide. This species undergoes cycloaddition reactions with a suitable ester of fumaric acid like the corresponding diethyl ester or dimethyl ester in a one-pot procedure to yield the corresponding N-protected trans racemic mixture of pyrrolidine-3,4-dicarboxylic acid diesters. The N-protecting group is changed to the corresponding Boc- or Z-protecting group via cleavage of the first N-pxotecting group via e.g. catalytical hydrogenation. For this the protected pyrrolidine is dissolved in a suitable solvent like methanol, ethanol, THF or ethyl acetate followed by addition of a catalyst like Pd/C (e.g. 10%) to the mixture. After that a hydrogen atmosphere is generated to cleave the first N-protecting group. The free amine is then again protected by addition of B0C2O or Z-Cl, respectively. The last step is the complete saponification of the diester to the corresponding diadd. The pyrrolidine diester is dissolved in suitable solvent system like methanol, ethanols THF, l,4-dioxane> water or mixtures thereof and a base like LiOH, NaOH, KOH, Na2CO3, K2CO3 or CS2CO3 is added. Monohydrolysis can be performed using enantioselective enzymes or chiral bases in suitable solvents already described ox in buffered aqueous systems. 2, Modifactions of pyrrolidine scaffolds: a) Starting from N'Boc-pyrrolidine-3>4-dicarboxylic acids, introduction of R2-NH-R3 General Procedure: N-protected pyrrolidine-3,4-dicarboxylic acid is dissolved in a suitable solvent like dichloromethane, DMF, acetonitrile, THF, NMP, DMA, etc, and activated with an amide coupling reagent like EDC, DIC, DCC, CDI, TBTU, HBTU, EEDQ, CIP, HOBt, HATU, PyBOP, PyBrOP, BOP, BOP-C1, TFFH, etc. at -10°C - 120°C. By adding one to two equivalents of the amine R -NH-R the corresponding monoamide is obtained after reaction for 0.5-120 h at -10°C to 120 °C. Repetition of this reaction by using the same coupling reagents as mentioned above or transformation of the acid into the corresponding acid chloride or anhydride by means of oxalyl chloride, thionylchloride, isobutylcarbamoyl chloride or related reagents, with R4-NH-Y yields the corresponding diamide. After deprotection under standard conditions like treatment with acids (e.g. HC1, trifluoracetic acid, HBr in glacial acetic acid) or hydrogenation in the case of the Z-protecting group the unprotected pyrrolidine-l,3-dicarboxamide is reacted "with suitable reagents to introduce R1. Suitable reagents LG-R include alkylhalogenides (chlorides, bromides, iodides), -trifLates, -para-nitrophenolates, -mesylates, acidchlorides, sulfonic acid chlorides, carbamoylchlorides, sulfamides, sulfamidoylchlorides, aldehydes, ketones etc. and can be reacted in solvents like dichloromethane, THF, acetonitrile, DMF, DMA, DMSO> NMP etc. with bases like DIEA, triethylamine, pyridine, N-methylmorpholine, Na2CO3) K2CO3, Cs2CO3 etc. b) Starting from N-Boc-pyrrolidine-S^dicarboxyiic acids, introduction of R4-NH- Y General Procedure: Like 2a) "with a different order of the reaction sequence. c) Starting from £,i?~N-Boc-pyrroMine-3,4-dicarboxylic acid-3-ethylester> introduction of R2-NH-R3 General Procedure: Like 2a) with a different order of the reaction sequence and saponifi cation at step 2 as described for procedure 1. d) Starting from iJ,-R-N-Boc-pyrrolidine-3,4-dicarboxylic acid-3-ethylester, introduction of R4-NH-Y General Procedure: Like 2c) with a different order of the reaction sequence. e) Starling from iU^-N-Boc-pyrrolidine-34-dicarbo:xylic acid-3-ethylester, introduction of R2-NH-R3 and R1 J Chiral I chiral 00 0^0 H Chira! i, u M Deprotection \ / /\ fl " r^N R3 \ / Q + WSB R3 W N-Y >0 HD^>=0 K >*O R2' ^0 cT o o^ ra o o J) ?1 CWrai 'j11 Chiral N N LG_R1 ^ N 1. Saponification f N —- R^ )—( R3, M. N —/ 'ci= O 2. Amide formation ■ N —/ '^ o R2' o O R4 R2' Xo M ) N-Y R4' V General Procedure: Like 2c) -with a different order of the reaction sequence. f) Starting from^i^-N-Boc-pyrrolidiiie-S^-dicarboxylic atid-3-ethylester, introduction of R4-NH-Y and R1 General Procedure: Like 2c) with a different order of the reaction sequence. Analogous reactions can be performed with the corresponding S,S enatioiners. Insofar as their preparation is not described in the examples, the compounds of formula (I) as well as all intermediate products can be prepared according to analogous methods or according to the methods set forth above. Starting materials are commercially available or known in the art Furthermore, the invention relates to compounds of formula (I) as defined above, when manufactured by a process as described above. In another embodiment, the invention relates to the intermediates, the compounds of formula (H), (III) or (IV) wherein R1, R2, R3, R4, R5, R7, R8, R9 and X have the significances given above. As described above, the compounds of formula (I) are active compounds and inhibit the coagulation factor Xa. These compounds consequently influence both platelet activation which is induced by this factors and plasmatic blood coagulation. They therefore inhibit the formation of thrombi and can be used for the treatment and/or prevention of thrombotic disorders, such as, amongst others, arterial and venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease (PAOD)> unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke (cerebral thrombosis) due to atrial fibrillation, inflammation and arteriosclerosis. The compounds of the present invention can also be used in the treatment of acute vessel closure associated with thrombolytic therapy and restenosis, e.g. after transluminal coronary angioplasty (PTCA) or bypass grafting of the coronary or peripheral arteries and in the maintenance of vascular access patency in long term hemodialysis patients. F.Xa inhibitors of this invention may form part of a combination therapy "with an anticoagulant with a different mode of action or with a platelet aggregation inhibitor or with a thrombolytic agent. Furthermore, these compounds have an effect on tumour cells and prevent metastases. They can therefore also be used as antitumoux agents. Prevention and/or treatment of thrombotic disorders, particularly arterial or deep vein thrombosis, is the preferred indication. The invention therefore also relates to pharmaceutical compositions comprising a compound as defined above and a pharmaceutically acceptable carrier and/or adjuvant The invention likewise embraces compounds as described above for use as therapeutically active substances, especially as therapeutically active substances for the treatment and/or prophylaxis of diseases which are associated with the coagulation factor Xa, particularly as therapeutically active substances for the treatment and/or prophylaxis of thrombotic disorders, arterial thrombosis, venous thrombosis, deep vein thrombosis, peripheral arterial ocdusive disease, unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke due to atrial fibrillation, inflammation, arteriosclerosis, acute vessel closure associated with thrombolytic therapy or restenosis, and/or tumour In another preferred embodiment, the invention relates to a method for the therapeutic and/or prophylactic treatment of diseases which are associated with the coagulation factor Xa, particularly for the therapeutic and/or prophylactic treatment of thrombotic disorders, arterial thrombosis, venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease, unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke due to atrial fibrillation, inflammation, arteriosclerosis, acute vessel closure associated Math thrombolytic therapy or restenosis, and/or tumour, which method comprises administering a compound as defined above to a human being or animal. The invention also embraces the use of compounds as defined above for the therapeutic and/or prophylactic treatment of diseases which are associated with the coagulation factor Xa, particularly for the therapeutic and/or prophylactic treatment of thrombotic disorders, arterial thrombosis, venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease, unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke due to atrial fibrillation, inflammation, arteriosclerosis, acute vessel closure associated with thrombolytic therapy or restenosis, and/or tumour. The invention also relates to the use of compounds as described above for the preparation of medicaments for the therapeutic and/or prophylactic treatment of diseases which are asscociated with the coagulation factor Xa, particularly for the therapeutic and/or prophylactic treatment of thrombotic disorders, arterial thrombosis, venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease, unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism* stroke due to atrial fibrillation, inflammation, arteriosclerosis, acute vessel closure associated with thrombolytic therapy or iestenosiSy and/or tumour. Such medicaments comprise a compound as described above. The inhibition of the coagulation factor Xaby the compounds of the present invention can be demonstrated with the aid of a chromogenic peptide substrate assay as described hereinafter. Factor Xa activity was measured spectrophotometrically in microtiter plates in a final volume of 150 pi using the following conditions: Inhibition of human factor Xa (Enzyme Research Laboratories) was tested at an enzyme concentration of 3 nM using the chromogenic substrate S-2222 (Chromogenix AB, Molndal, Sweden) at 200 nM. The reaction kinetics of lite enzyme and the substrate were linear with both time and the enzyme concentration. The inhibitors were dissolved in DMSO and tested at various concentrations up to 100 pM. The inhibitors were diluted using HNPT buffer consisting of HEPES lOOmM, NaCl 140mM, PEG 6000 0.1%-and Tween 80 0.02%, pH 7.8. The cleavage of S-2222 by human factor Xa was followed at 405 nm for 5 minutes at room temperature. The velocity of the reaction was determined by the autoreader from the slope of the linear regression fit to 7 time points (1 minute). The initial velocity for each inhibitor concentration was determined by the slope of at least 4 time points in the linear phase by a linear regression fit (mOD/min ). Apparent dissociation constants K* were calculated according to Cheng and Prusoff [Cheng, Y. G; Prusoff, W. H. Relationship between the inhibition constant (KO and the concentration of the inhibitor that causes 50 percent inhibition (IC50) of an enzyme reaction. Biochem. Pharmacol 1973,22, 3099-3108.] based on the IC50 and the respective Km, determined previously (K* = IC50/ (1+S/Km)). The Km for the substrate used was determined under the conditions of the test with at least 5 substrate concentrations ranging from 0.5 to 15 times Km. [Lottenberg R, Hall JA, Blinder M> Binder EP, Jackson CM., The action of thrombin on peptide p-nitroanilide substrates. Substrate selectivity and examination of hydrolysis under different reaction conditions. Biochim Biophys Ada. 1983 Feb 15; 742(3):539-57]. according to Eadie [Eadie G.S. The inhibition of cholinesterase by physostigmine and prostigmine. J. Biol. Chem, 1942,146, 85-93.]. The Km for S-2222 amounted to 613 fiM. The activity of the low molecular weight substances can, moreover be characterized in the "prothrombin time" (PT) clotting test. The substances are prepared as a 10 mM solution in DMSO and thereafter made up to the desired dilution in the same solvent Thereafter, 0.25 ml of human plasma (obtained from whole blood anticoagulated with 1/10 volume of 108 mM Na citrate) was placed in the instrument-specific sample container. In each case 5 yd of each dilution of the substance-dilution series was then mixed with the plasma provided. This plasma/inhibitor mixture was incubated at 37°C for 2 minutes. Thereafter, there were pipetted to the semi-automatic device (ACL, Automated Coagulation Laboratory (Instrument Laboratory)) 50 pi of plasma/ inhibitor mixture in the measurement container. The clotting reaction was initiated by the addition of 0.1 ml of Dade® Innovin® (recombinant human tissue factor combined with calcium buffer and synthetic phospholipids, Dade Behring, Inc., Cat. B4212-50). The time up to the fibrin cross-linking was determined photooptically from the ACL. The inhibitor concentration, which brought about a doubling of the PT clotting time, was determined by fitting the data to an exponential regression (XLfit). The compounds of the present invention can furthermore be characterised by the Activated Partial Thromboplastin time (aPTT). This coagulation test can e.g. be run on the ACL 300 Coagulation System (Instrumentation Laboratory) automatic analyzer. The substances are prepared as a 10 mM solution in DMSO and thereafter made up to the desired dilution in the same solvent. The test is performed with the Dade® Actin® FS Activated PTT reagent (purified soy phosphatides in l.OxlO^M ellagic acid, stabilizers and preservative, Dade Behring, Inc., Cat. B4218-100) Thereafter, 0.25 ml aliquots of human plasma (obtained from whole blood anticoagulated with 1/10 volume of 108 mM Na citrate) are spiked with 5 pi of test compound in at least 6 concentrations. 50 pi plasma at 4°C containing 1/50 vol. inhibitor in solvent are incubated with 50 pi Dade® Actin® FS Activated PTT reagent in water at 37°C for 3 min., then 50 pi CaCl2.2H2O 25 mM in water at 37°C are added. The time up to the fibrin cross-linking was determined photooptically from the ACL. The inhibitor concentration, which brought about a doubling of the APTT clotting time, was determined by fitting the data to an exponential regression (XLfit). The Ki values of the active compounds of the present invention preferably amount to about 0.001 to 50 pM, especially about 0.001 to 1 jiM. The PT values preferably amount to about 1 to 100 pM, especially to about 1 to 10 pM. The aPTT values preferably amount to about 1 to 100 pM, especially to about 1 to 10 pM. The compounds of formula I and/or their pharmaceuticaUy acceptable salts can be used as medicaments, e.g. in the form of pharmaceutical preparations for enteral, parenteral or topical administration. They can be administered, for example, perorally* e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions, rectally, e.g. in the form of suppositories, parenterally, e.g. in the form of injection solutions or suspensions or infusion solutions, or topically, e.g. in the form of ointments, creams or oils. Oral administration is preferred. The production of the pharmaceutical preparations can be effected in a manner which will be familiar to any person skilled in the art by bringing the described compounds of formula I and/or their pharmaceuticaUy acceptable salts, optionally in combination with other therapeutically valuable substances, into a galenical administration form together with suitable, non-toxic, inert, therapeutically compatible solid or liquid carrier materials and, if desired, usual pharmaceutical adjuvants. Suitable carrier materials are not only inorganic carrier materials, but also organic carrier materials. Thus, for example, lactose, corn starch or derivatives thereof, talc, stearic acid or its salts can be used as carrier materials for tablets, coated tablets, dragees and hard gelatine capsules. Suitable carrier materials for soft gelatine capsules are, for example, vegetable oils, waxes, fats and semi-solid and liquid polyols (depending on the nature of the active ingredient no carriers might, however, be required in the case of soft gelatine capsules). Suitable carrier materials for the production of solutions and syrups are, for example, water, polyols, sucrose, invert sugar and the like. Suitable carrier materials for injection solutions are, for example, water, alcohols, polyols, glycerol and vegetable oils. Suitable carrier materials for suppositories are, for example, natural or hardened oils, waxes, fats and semi-liquid or liquid polyols. Suitable carrier materials for topical preparations are glycerides, semi-synthetic and synthetic glycerides, hydrogenated oils, liquid waxes, liquid paraffins, liquid fatty alcohols, sterols, polyethylene glycols and cellulose derivatives. Usual stabilizers, preservatives, wetting and emulsifying agents, consistency-improving agents, flavour-improving agents, salts for varying the osmotic pressure, buffer substances, solubilizers, colorants and masking agents and antioxidants come into consideration as pharmaceutical adjuvants. The dosage of the compounds of formula I can vary within wide limits depending on the disease to be controlled, the age and the individual condition of the patient and the mode of administration, and will, of course, be fitted to the individual requirements in each particular case. For adult patients a daily dosage of about 1 to 1000 mg, especially about 1 to 300 mg, comes into consideration. Depending on severity of the disease and the precise pharmacokinetic profile the compound could be administered with one or several daily dosage units, e.g. in 1 to 3 dosage units. The pharmaceutical preparations conveniently contain about 1-500 mg, preferably 1-100 mg, of a compound of formula I. The following Examples serve to illustrate the present invention in more detail. They are, however, not intended to limit its scope in any manner. Examples Example 1 trans-(3RS,4RS)-l-Methanesulfo^ acid 3-[(4- chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p^Ti.din-l-yl)-phenyl]-ainide} According to the general method 2a) Stepl: trai2S'(3RSy4RS)'l'Benzyl-p)n'olidme-3}4-dicarhox}dic add diethyl ester la Fumaric acid diethylester (21.6 g; 0.126 mol) is dissolved in toluene (900 ml) and heated at 105 °C. A mixture of N-benzylglycine (25 g; 0.151 mol) and paraformaldehyde (25.36 g; 0.844 mol) is added in 4 g portions to the refluxing solution. After completion of the addition the mixture is heated for 18 h at 105°C. The mixture is then evaporated to dryness and suspended in n-hexane. The insoluble material is filtered off and the remaining solution is evaporated to dryness. The crude product is used for the next step without further purification. Yield: 32.5 g (70.3 %), ESI-MS: m/z = 306 [M+H]+ Step 2: traiis-(3RS,4RS)-Pyrrolidine-l,3,4-tricarbox)dic acid tert-butyl ester diethyl ester lb Under argon-atmosphere compound la (32.5 g; 0.106 mol) and di-£er£-butyldicarbonat (24.4 g; 0.112 mol) are dissolved in ethanol (650 ml). After that palladium on charcoal (10%; 3.4 g; 0.0034 mol) is added under argon-atmosphere and the argon-atmosphere is changed to hydrogen-atmosphere. After 2 h at 25°C the hydrogenation is completed and palladium on charcoal is filtered off. The filtrate is evaporated to dryness and the residue is purified with flash chromatography over silica gel (700 g) using n-heptane/ethyl acetate (2:1) as eluent. Yield: 25.4 g (75.7 %), ESI-MS: m/z = 316 [M+H]+ Step 3: trans-(3RS>4RSyPyrrolidine'l)3i4-tricarboxylic acid tert-butyl ester 1c Compound lb (1 g> 3.17 mmol) was dissolved in of THF (8 ml), and 80 mL of water was added. The reaction mixture was immersed in an ice-water bath and cooled to 0 C. To this reaction mixture, 96 ml of 0.25 N NaOH was added in small portions with stirring until the consumption of the starting diester was detected by thin-layer chromatography. The reaction was stirred at the same temperature for about 30 min to 1 h> and the reaction mixture was acidified with 1 N HC1 at 0 °Q saturated with NaCl, extracted with ethyl acetate four times (each 100 ml), and dried with sodium sulfate. The organic phase is evaporated to dryness and dried in vacuo. Yield: 0.68 g (82.7%), ESI-MS: m/z = 258 [M-H]" Step 4: trzii.&-(3RS>4RS)-4-(4-Chlorophenylcarbamoyl)-fy add 1-tert-butyl ester Id Compound lc (2.25 g; 9 mmol) is suspended in acetonitriie (30 ml) and N,N-diisopropyl ethyl amin (3.03 ml; 17 mmol) is added at 25 °C. After 20 min a dear solution is obtained and 1 -(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDCI (2.0 g; 10 mmol) and 1-hydroxybenzotriazole HOBt (1.41 g; 10 mmol) is added After stirring for 30 min at 25°C 4-chloroaniline (1.11 g; 9 mmol) is added to the reaction mixture. The mixture is stirred for 18 h at 25°C, evaporated to dryness and dissolved in ethyl acetate (100 ml). The organic phase is washed with 0.1 N HC1 (2 x 100 ml), water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. Yield: 1.08 g (33.7%), ESI-MS: m/z = 368 [M-H]", C]-pattern Step 5: l~(4-Amino-3-fluoro--phenyl)-lH-pyridin'2-o?te le 4-Bromo-2-fluoroaniline (13.0 g; 68 mmol), 2-hydroxypyridine (9.11 g; 96 mmol), 8-hydroxyquinoline (1.5 g; 10 mmol) are dissolved under argon in DMSO (40 ml). To this solution K2CO3 (10.4 g; 75 mmo!) and Cul (1.95 g; 10 mmol) are added and the resulting suspension is heavily stirred under argon at 150°C for 18 h. The mixture is evaporated to dryness under reduced pressure and the final residue is chromatographed over silica gel (400 g) using dichloromethane/methanol as eluents. The obtained crude product is recrystallized with diethyl ether to yield an off-white solid. Yield:'2.80 g (20.0 %), ESI-MS: m/z = 205 [M+H]+ Step 6: tran$-(3RS,4RS)-Pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)' amide] 4-{{2-fluoro~4-(2~oxo-2H-pyridin-l-yl)-phertyl]-amide} hydrochloride If Compound Id (0,8 g; 2 mmol) is dissolved in thionylchloride (3.93 ml; 54 mmol), after 30 min stirring at 25 °C l-(4-amino-3-fluoro-phenyl)-lH-pyridin-2-one (compound le, 0.443 g; 2 mmol) is added under cooling. The mixture is stirred for 18 h at 25 °C, evaporated to dryness and recrystallized from diethyl ether yielding compound I/as light brown solid as hydrochloride. Yield: 0.872 g (81.8 %), ESI-MS: m/z = 455 [M+Hr> Cl-pattern Step 7: traiis-(3RSy4RS)'l'Me^ia7iesulfonyl-pynolidine'334-dicarboxylic acid 3-[(4-chloro~phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)~phenyl]-amide} Ig Compound If (803 mg; 0.177 mmol) is dissolved in acetonitrile (3 ml) under addition of N>N-diisopropyl ethyl amine (45.75 mg; 61.8 \xl; 0.354 mmol). Methanesulfonylchloride (40.6 mg; 0.354 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 11.2 mg (11.9 %), ESI-MS: m/z = 533 [M+H]+, Cl-pattern Example 2 trans-(3RS>4RS)-l-Fonnyl»p)TTondine»354-dicarboxyHcacid3-[(4-cUoro-phenyl)-amide] 4-{[2-fluoro-4~(2-oxo-2H-pyridin-l-yl)-phenyI]-amide} The compound of example 2 was prepared as described for example 1 with the exception of step 7 Step 7: tra7i$-(3RS,4RS)-l-Fonn)d~p)rrolidine-3,4-dicarboxylic add 3-[(4-chloro-phenyl)-amidt] 4-{{2-fluoro-4-(2-oxO'2H-pyridin-l-yl)-phenyl]-amide} 2 . Compound If (80.3 mg; 0.177 mmol) is dissolved in acetonitrile (3 ml) under addition of N,N-diisopropyl ethyl amine (22.9 mg; 30.9 yl; 0.177 mmol). 4-Nitrophenylfonniate (29.6 mg; 0.177 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 13.8 mg (16.1 %), ESI-MS: m/z = 483 [M+H]+> Cl-pattern Example 3 trans-(3RS>4RS)-{3-(4-Chloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidin-l-yl}-acetic acid ethyl ester The compound of example 3 was prepared as described for example 1 with the exception of step 7 Step 7: trans-(3RS,4RS)-{3-(4-Chbro-phenylcarbamoyl)-4'[2-flu^ pyridiit-~l-yl)-phenylcarbamoyl]--pyrrolidin-l-yl}-acetic add ethyl ester 3 Compound If (80,3 mg; 0.177 mmol) and K2CO3 (69.0 mg; 0.5 mmol) are suspended in acetonitrile (3 ml). After that bromo acetic acid ethyl ester (32.5 mg; 0.195 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC . chromatography. Yield* 18.8 mg (19.6 %), ESI-MS: m/z = 541 [M+Hf5 Cl-pattern Example 4 trans-(3RS,4RS)- l-Carbamoylmethyl-p^TroHdine-S^dicarboxyiic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxO"2H-pyridin-l"yl)-phen7l]»amide} The compound of example 4 was prepared as described for example 1 -with the exception of step 7 Step 7: Uans-(3RS>4RS)A-Carbamoylmethyl-pynolid^ add 3-[(4- chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-pheiiyl]-amide} 4 Compound If (80.3 mg; 0.177 mmol) and K2CO3 (69.0 ing; 0.5 mmol) are suspended in acetonitrile (3 ml). After that 2-bromo-acetamide (27.0 mg; 0.195 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 10.8 mg (11.9 %), ESI-MS: m/z = 512 [M+H]+> Cl-pattern Example 5 trans-(3RS,4RS)-l-Cyanomethyl-pyrrolidine-3,4-dicarboxylic acid 3- [(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-1 -yl)-phenyl]-amide} The compound of example 5 was prepared as described for example 1 with the exception of step 7 Step 7: trans- (3RS,4RS)-1-Cyanomethyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4~(2-oxO'2H-pyridi7t-l~yl)-phenyl]-amide} 5 Compound If (80.3 mg; 0.177 mmol) and K2CO3 (69.0 mg; 0.5 mmol) are suspended in acetonitrile (3 ml). After that 2-bromo-acetonitrile (23.4 mg; 0.195 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 10.4 mg (11.9 %), ESI-MS: m/z = 494 [M+H]+, Cl-pattern Example 6 lxans-(3RS,4RS)-l-(3,33-Trifluoro-propyl)-pyrroHdine-354-dicarbosylic acid 3- [(4-chloro-phenyl)-amide]-4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]- amide} The compound of example 6 was prepared as described for example 1 with the exception of step 7 Step 7: tram-(3RS,4RS)-l-(3,3,3-TrifiuoTO-propyl)-p)rro^ add 3-[(4-chhro-phenyl)-amide]-4-{[2-ffa 6 Compound If (80.3 ing; 0.177 mmol) and K2CO3 (69.0 mg; 0.5 mmol) are suspended in acetonitrile (3 ml). After that 3-bromo-l,l,l-txifluoropropane (34.5 mg; 0.195 mmol) and Ag2O (45.2 mg; 0.195 mmol) is added and the mixture is stirred for 18 h at 80 °C The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 19.7 mg (20.2 %), ESI-MS: m/z = 551 [M+H]+, Cl-pattern Example 7 (3R,4R)-l-Metiianesiilfon7l-pyrrolidine-3,4-dicarbox7lic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yi)-phenyl]-amide} According to general method 2c) Step 1: (3R,4R)-Pyrrolidine-ly3,4-tricarboxylic add-1-tert-butyl ester-3-ethyl ester 7a The stereoselective mono saponification of the racernic mixture of compound lb to compound 7a and the correpsonding S,S-enantiomer is described in: R.M. Rodriguez Sarmiento, B. Wirz, H. Iding, Tetrahedron Asymmetry, 14> 2003, 1547-1551. Step 2a: (3RAR)'4~(4-Chlorophe7zylcarbamoyl)'p)Trolidi?te'lf3-dicarboxylic acid 1-tert-butyl ester- 3-ethyl ester 7b Compound 7a (4.91 g; 17.1 mmol) is suspended in acetonitrile (25 ml) and N,N-diisopropyl ethyl amin (3.58 ml; 20.5 mmol) is added at 0 °C. Bis (2-oxo-3-oxazolidinyl) phosphinic chloride BOP-C1 (5.22 g; 20.5 mmol) is added as a solid and after stirring for 30 min at 0°C 4-chloroaniline (2.18 g; 17.1 mmol) is added to the reaction mixture. The mixture is stirred for 2 h at 0°C, evaporated to dryness and dissolved in ethyl acetate (ml). The organic phase is washed with 0.1 N HC1 (2 x ml), with saturated aquous Na2CC>3 solution, water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography. Yield: 4.7 g (69.3 %), ESI-MS: m/z = 395 [M-H]"> Cl-pattern Step 2b: (3RJ4R)-4'(4'Chlorophenylcarbamoyl)-pynolidine-l>3'dicarboxylic acid 1-tert-butyl ester 7c The ester obtained from step 2a (4.07 g; 10.3 mmol) is dissolved in a mixture of THF/water (1:1; 40 ml). LiOH monohydrate (0.947 g; 22.6 mmol) is added to the mixture and complete saponification is obtained after stirring for 18 h at 25°C. The mixture is acidified with. IN aq. HC1 and diluted with ethyl acetate (100 ml). The organic phase is washed with brine (100 ml) and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. Yield: 3.28 g (86.7 %)> ESI-MS: m/z = 367 [M-H]\ Cl-pattern Step 3: (3R,4R)-Pyrrolidine'3}4~dicarboxyUc acid 3-[(4-chloro-pheityl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} hydrochloride 7d Compound 7c (2.2 g; 5.96 mmol) is dissolved in thionylchloride (10 ml) and stirred at 25°C for 30 min. After that l-(4-amino-3-fluoro-phenyl)-lH-pyridin-2-one (compound le; 1.22 g; 5.96 mmol) is added and the reaction mixture is stirred for 18 h at ambient temperature. The mixture is evaporated to dryness and the crude product is recrystallized from diethylether several times to yield compound 7d as light brown solid Yield: 2.92 g (99.7 %), ESI-MS: m/z = 455 [M+H]+, Cl-pattern Step 4: (3RAR)'l-MethaiiesulfonyUp)nrolidme'3A'dicarboxylic add 3-[(4-chloro-pheityl)-a?nide] 4~{[2-fluoro-4-(2-oxo-2H-pyridinA~yiyphaiyl]-amide} 7e Compound 7d (300 mg; 0.61 mmol) is dissolved in acetonitrile (5 ml) under addition of N,N-diisopropyl ethyl amine (210 pi; ■ 1.22- mmol). -Methanesulfonylchloride (140 mg; 1.22 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 170 mg (5.22 %), ESI-MS: m/z = 533 [M+H]+, Cl-pattern Example 8 (SR^^-l-Ethanesulfonyl-pyrrolidine-Sj^dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-£luoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 8 was prepared according to the methods described for example 7. ESI-MS: m/z = 547 [M+H]+> Cl-pattern Example 9 (3R,4R)-l-Propanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyI]-amide} The compound of example 9 was prepared according to the methods described for example 7. ESI-MS: m/z = 561 [M+H]+, Cl-pattern Example 10 (3R)4R)-l-(Propane-2-sulfonyI)-pyrrolidine-3J4-dicarbox7lic acid 3-[(4-chloro-phenyi)-amide] 4-{[2-fluoro-4- (2-oxo-2H-pyridin-1 -yl)-phenyl] -amide} The compound of example 10 was prepared according to the methods described for example 7. ESI-MS: m/z = 561 [M+H]+, Cl-pattern Example 11 (3R>4R)-l«(2>2>2"Trifluoro-ethanesulfonyl)-pyrroUdine-3>4-dica^^ acid 3- [ (4-chloro-phenyl)-amide] 4-{ [2-fluoro-4- (2-oxo-2H-pyridin- l-yl)-phenyl] - amide} The compound of example 11 was prepared according to the methods described for example 7. ESI-MS: m/z = 601 [M+H]+, Cl-pattern Example 12 (SR^RJ-l-Dimethylsulfainoyl-pyrrolidine-S^dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4- {[2-fluoro-4- (2-oxo-2H-pyridin* 1 -yl)-phenyl] - amide} The compound of Example 12 was prepared according to the methods described for example 7. ESI-MS: m/z = 562 [M+H]+, Cl-pattern Example 13 (3R,4R)«l-Acetyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4»chIoro-phenyI)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of Example 13 was prepared according to the methods described for example 7. ESI-MS: m/z = 497 [M+H]+, Cl-pattern Example 14 (3R,4R>3- (4-Chloro-phenylcarbamoyl)-4- [2-fluoro-4- (2-oxo-2H-pyridin- l-yl)-phenylcaxbamoyl] -pyrrolidine-1 -carboxylic acid methyl ester The compound of example 14 was prepared according to the methods described for example 7. ESI-MS: m/z = 513 [M+H]+, Cl-pattern Example 15 (3R»4R)-1- (2-Fluoro-ethyl)-pyrrolidine-3 ,4-dicarboxylic acid 3- [ (4-dhloro-phenyl)-amide] 4-{[2~fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 15 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in acetonitrile (2 ml) under addition K2CO3 (56 mg; 0.4 mmol). 2-Fluoroethylbromide (59 mg; 0.41 mmol) and Ag2O (47 mg; 0.2 mmol) is added to the reaction mixture. The mixture is stirred at 80°C until a fall conversion to example 23 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 20 mg (18.9 %), ESI-MS: m/z = 501 [M+H]+, Cl-pattern Example 16 (3R,4R)-3-(4-CUoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamo)d]-pyrrolidine*l-carboxyKc acid ethyl ester The compound of example 16 was prepared according to the methods described for example 7. ESI-MS: m/z = 527 [M+H]+> ei-patterrr Example 17 (3R>4R)-3-(4-CWoro-phenyIcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-p^din-l-yl)-phenylcarbamoylj-pyrrolidine-l-carboxylic acidpropyl ester The compound of example 17 was prepared according to the methods described for example 7, ESI-MS: m/z = 541 [M+H]+> Cl-pattern Example 18 (3R,4R)-3-(4»Chloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidine-l-carboxylic acid isopropyl ester The compound of example 18 was prepared according to the methods described for example 7. ESI-MS: m/z = 541 [M+H]^, Cl-pattern Example 19 (3R»4R)- l-(Pyrrolidine- l-carbonyl)-pyrrolidine-3,4-dicarboxyiic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H"pyridin-l«yl)-phenyL]-amide} The compound of example 19 was prepared according to the methods described for example 7. ESI-MS: m/z = 552 [M+H]\ Cl-pattern Example 20 (3 S,4S)-1 -Methanesulfonyl-pyrrolidine-3>4-dicarboxylic acid 3- [(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4- (2-oxo-2H-pyridin-1 -yl)~phenyl]-amide} The compound of example 20 was prepared according to the methods described for example 7 starting from the (3S, 4S)-enantiomer. ESI-MS: m/z = 533 [M+H]+> Cl-pattern Example 21 (3R,4R)-l-Sxdfamoyl-pyrrolidine-3>4-dicarboxylic acid 3-[(4n:hloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l"yl)"phenyl]-amide} The compound of example 21 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in diglyme (1 ml). The mixture is heated at 160 °C and a solution of sulfamide (23 mg; 0.24 mmol) in diglyme (1 ml) is dropped to the reaction mixture within 5 min. The reaction mixture is heated at 160 °C until a full conversion to example 21 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC Yield: 4 mg (3.7 %), ESI-MS: m/z = 534 [MH-H]+5 Cl-pattern Example 22 (3R)4R)-l*Formylpyrrolidine'3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4- {[ 2-fluoro-4- (2-oxo-2H-pyridin-1 -yl) -phenyl] -amide} The compound of example 22 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in acetonitrile (2 ml) under addition of N>N-diisopropyl ethyl amine (30 (il; 0.2 mmol). Formic acid-4-nitrophenyi ester (34 mg; 0.2 mmol) is added to the reaction mixture. The mixture is stirred at ambient temperature until a full conversion to example 22 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 40.4 mg (41.1 %), ESI-MS: m/z = 483 [M+H]+, Cl-pattern Example 23 (3R>4R)-l-(2,2>2-Trifluoro-ethyI)-pyrrolidine-3,4-dicafboxjdic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-ainide} The compound of example 23 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (80 mg; 0.16 mmol) is dissolved in dichloromethane (2 ml) under addition of NJSI-diisopropyl ethyl amine (60 \sl; 0.41 mmol). 2>2>2-Trifluoroethyltriflate (57 mg; 0.24 mmol) is added to the reaction mixture. The mixture is stirred at ambient temperature until a full conversion to example 23 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 10.0 mg (11.4 %), ESI-MS: m/z = 537 [M+H]+, Cl-pattern Example 24 (3R,4R)- l-(2>2-Difluoro-ethyl)-pyrrolidine-3>4-dicarboxylic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p^Tidin-l-yl)-phenyl]-amide} The compound of example 24 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in acetonitrile (2 ml) under addition K2CO3 (56 mg; 0.4 mmol). 2,2-Difluoroethylbromide (59 mg; 0.41 mmol) and Ag^O (47 mg; 0.2 rnrnol) is added to the reaction mixture. The mixture is stirred at 80°C until a full conversion to example 23 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 20 mg (18.9 %), ESI-MS: m/z = 519 [M+H]+, Cl-pattern Example 25 ■ (3R)4R)-l-(2-Hydroxy-etiiyl)-pyrroUdhie--3)4-dicarl)Oxylic acid 3- [(4-chloro-phenyl)-amide] 4-{[2-£luoro-4-(2-oxo-2H-pyridin-l-yi)-phenyi]»ainide} The compound of example 25 was prepared according to the methods described for example 24. ESI-MS: m/z = 500 [M+H]+, Cl-pattern Example 26 (3R,4R)-1-Methylcarbamoy]meft^ acid 3-[(4- chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 26 was prepared according to the methods described for example 24. ESI-MS: m/z = 526 [M+H]+, Cl-pattern Example 27 (3R,4R)-l-Isopropyl-pyrrolidine"3J4-dicafboxylic acid 3~[(4-chloro-phenyl)-ainide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 27 was prepared according to the methods described for example 24 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in a mixture of methanol and acetic acid (9:1; 2 ml). Aceton (24 mg; 0.41 mmol) is added and the reaction mixture is stirred for 30 min at 25°C. After that NaBH3CN (45 mg; 0.71 mmol) is added to the mixture. After stirring for 18 h at ambient temperature the reaction mixture is treated once again with aceton (24 mg; 0.41 mmol) and NaBHsCN (45 mg; 0.71 mmol) and stirred at 80 °C for 18 h. After that the mixture is evaporated to dryness and purified with preparative HPLC. Yield: 3 mg (3 %), ESI-MS: m/z = 497 [M+H]+, Cl-pattern Example 28 (3R)4R)-l-Methanesulfonyl-pyrroIidine-3,4-dicarboxylic acid 3-{[2-fLuoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} 4-[(lH-indol-5-yl)-amide] According to general method 2d) Step 1: (3RAR)'Pyrrolidine-l,3A-tricarbox)rlic acid-1-tert-butyl ester-3-ethyl ester 7a The stereoselective mono saponification of the racemic mixture of compound 1b to compound 7a and the correpsonding S,S-enantiomer is described in: R.M. Rodriguez Sanniento, B. Wirz, H. Iding, Tetrahedron Asymmetry, 14, 2003, 1547-1551. Step 2: (3RM)-4'[2-Fluoro~4-(2'OXo-2H'pyndin'l-yl)-phenykarbamoyl]-py7Tolidine-l,3-dicarbox)dic add 1 -tert-butyl ester 3-ethyl ester 28b Compound 7a (1.85 g; 6 mmol) is suspended in acetonitrile (20 ml) and N,N-diisopropyl ethyl amin (1.65 ml; 10 mmol) is added at 25 °C. BOP-C1 (2.46 g; 10 mmol) is added as a solid and after stirring for 30 min at 25°C l-(4-amino-3-fluoro-phenyl)-lH-pyridin-2-one (1.45 g; 7 mmol) is added to the reaction mixture. The mixture is stirred for 4 d at 25°C, evaporated to dryness and dissolved in ethyl acetate (200 ml). The organic phase is washed 'with 2 N HC1 (50 ml), with 10% aqueous Na2CC>3 solution, water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography. Yield: 1.77 g (58.1 %), ESI-MS: m/z = 472 [M-H]- Step 3: (3R,4R)-4- [2-¥luoro-4- (2-oxo-2H-pyridin-1 -yl)-phmylcarbamoyl]-pyrrolidine-3-carbox)>lic add ethyl ester hydrochloride 28c Compound 28b (5.37 g; 11 mmol) is dissolved in 6 N HC1 in isopropanol (42 ml) and the mixture is stirred for 2 h at 25°C. The mixture is evaporated to dryness and the crude product is recrystallized from diethylether several times to yield compound 28c as an off-white solid. Yield: 4.89 g (105.2%), ESI-MS: m/z = 374 [M+H]+ Step 4: (3R,4R)-4-[2-Muoro-4-(2-oxo-2H-p)ridi77'l-yl)-phe7rylca^ methane-sulfonyl-pyrrolidiiie-3-carboxylic add ethyl ester 28d Compound 28c (3.1 g; 8 mmol) is suspended in acetonitrile (20 ml) under addition of N,N-diisopropyl ethyl amine (3.24 ml; 19 mmol). Methanesulfonylchloride (1.3 g; 11 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dqmess and purified by silica gel chromatography. Yield: 3.5 g (102.5 %), ESI-MS: m/z = 450 [M-H]~ Step 5: (3R,4R)-4-[2-Ruoro-4-(2-oxo-2H-pyridi77'l-yl)-phenylcarbamoyl]-l-methane~sulfonyl-pyrrolidine-3-carboxylic add 28e Compound 28d (3.7 g; 8 mmol) is dissolved in a mixture of 1,4-dioxane/water (1:1; 30 ml). LiOH monohydrate (1.03 g; 25 mmol) is added.to the mixture and complete saponification is obtained after stirring for 24 h at 25°C. The mixture is evaporated to dryness- and dissolved in ethyl acetate and the product is extracted with saturated aqueous Na2CO3 solution. The aqueous phase is cooled to 10 °C and acidified with 25% aqueous HC1 solution until pH = 1. The product is extracted several times with ethylacetate (3 x 100 ml). The combined organic phases are washed with brine and dried over Na2SC>4. After filtration the organic phase is evaporated to dryness. Yield: 1.57 g (45.2 %), ESI-MS: m/z = 422 [M-H]" Step 6: (SR^yi'MethaiiesulfonyJ'pyrrolidiyte'S^dicarboxylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridin-l~yl)~phmyl]-amide} 4-[(lH-indol-5-yl)-amide] 28f Compound 28e (100 mg; 0.236 mmol) is suspended in acetonitrile (1 ml) and N,N-diisopropyl ethyl amin (60 |ii; 0.354 mmol) is added at 25 °C. BOP-C1 (90 rng; 0. 354 mmol) is added as a solid and after stirring for 30 min at 25°C 5-amino indole (34 mg; 0.286 mmol) is added to the reaction mixture. The mixture is stirred for 18 h at 25°C, evaporated to dryness and purified by silica gel chromatography. Yield: 88 mg (69.3 %), ESI-MS: m/z = 538 [M+Hf Example 29 (3R^R)-l-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridin-1 -yl) -phenyl] -amide} 4- [ (4-methoxy-phenyl) -amide] The compound of example 29 was prepared according to the methods described for example 28. ESI-MS: m/z = 529 [M+H]+ Example 30 (3R,4R)- l-MethanesulfonyI-pyrrolidine-3,4"dicarboxylic acid 3- [(3-chloro-4-methoxy-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)7ridin-l-yl)-phenyl]-amide} The compound of example 30 was prepared according to the methods described for example 28. ESI-MS: m/z = 563 [M-f H]+, Cl-Pattern Example 31 (3R,4R)- l-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3- [ (3-fluoro~4-methoxy-phenyl)-ainide] 4- {[2-fluoro-4-(2-oxo-2H-pyridin-1 -yl)-phenyl] -amide} The compound of example 31 was prepared according to the methods described for example 28. ESI-MS: m/z = 547 [M+H]+ Example 32 (3RJ4R)-l-MeAanesiilfon7l-pyrroKdine--3)4-dicarboxyiic acid 3-[(4-chloro-3-£luoro-phenyl)-ajnide]4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yi)-phenyl]-ainide} The compound of example 32 was prepared according to the methods described for example 28. ESI-MS: m/z = 551 [M+H]+, Cl-Pattern Example 33 (3R54R)-l-Methanesxilfon7l-pyrrolidine-3)4-dicarbox7lic acid 3-[(4-chloro-2-ftuoro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 33 was prepared according to the methods described for example 28. ESI-MS: m/z = 551 [M+H]+, Cl-Pattern Example 34 (3R,4R)-l-Methanesulfonyl-pyrrolidine-3>4-dicarboxylic acid 3-[(2-amino-4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 34 was prepared according to the methods described for example 28. ESI-MS: m/z = 548 [M+H]+> Cl-Pattern Example 35 (3R)4R)-l-Methanesulfonyl-pyrroIidine-3,4-dicarboxyUc acid 3-[(4-chloro-phenyl)-methyl-ainide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)«phenyl]»amide} The compound of example 35 was prepared according to the methods described for example 28. ESI-MS: m/z = 547 [M-hH]+, Cl-Pattern Example 36 (3R?4R)-l-Methanesxdfonyl-pyrrolidine-3,4-dicarboxylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}4-[(lH-indazol-5-yl)-amide] The compoimd of example 36 was prepared according to the methods described for example 28. ESI-MS: m/z = 539 [M+H]+ (3R)4R)-l-MetiiajQesulfon7l-pyrroUdine-3)4-dic^xboxyiic acid 3-[(5-chloro-pyridin-2-yi)-amide] 4-{ [2-fluoro«4- (2-oxo-2H-pyridin-1 -yl)-phenyl] -amide} The compound of example 37 was prepared according to the methods described for example 28 with the exception of step 6. Step 6: Compound 28e (35 mg; 0.083 mmol) is dissolved under argon in thionylchlorid (0.03 ml; 0.413 mmol) to generate the corresponding acidchlorid. The mixture is stirred for 30 min at 25 °G 2-Amino-chloro pyridine is dissolved in THF and NaH suspension in oil (55%; 24 mg; 0.58 mmol) is added under hydrogen evolution. The mixture is stirred for 30 min at 25°C. The corresponding addchloride solution is added to the reaction mixture of the deprotonated 2-amino-chloro pyridine. The combined suspensions are stirred for 7 d at 25°C. The reaction suspension is evaporated to dryness and purified by silica gel chromatography. Yield: 36 mg (81.5 %), ESI-MS: m/z = 534 [M+H]+, Cl-Pattern Example 38 (3R,4R)*l-Methanesulfonyl-pyrrolidine-3>4-dicarbox5iic acid 3-(4-chloro-benzylamide) 4- {[2-fluoro-4~ (2-oxo-2H-pyridin~l -yl)-phenyl] -amide} The compound of example 38 was prepared according to the methods described for example 28. ESI-MS: m/z = 547 [M+H]+, Cl-Pattern Example 39 (3R,4R)-l-Methanesxilfonyl"pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro- phenyl)-amide] 4-{[2-fluoro-4-(3-methoxy-2-oxo-2H-pyridin-l-yl)-phenyl]- amide} According to general method 2e) Step 1; (3R,4R)-P)nTolidine-l,3t4-triearboxyIic add-1-tert-butyl ester-3-ethyl ester 7a The stereoselective mono saponification of the racemic mixture of compound ib to compound 7a and the correpsonding S,S-enantiomer is described in: R.M. Rodriguez Sarmiento, B. Wirz, H. Iding, Tetrahedron Asymmetry, 14, 2003, 1547-1551. Step 2a: (3R,4R)-4-(4-Chlorophenylcarba?noyl)'p)nrolidine-l,3-dicarboxylic acid 1-tert-butyl ester-3-ethyl ester 39 b Compound 7a (1 g; 3.48 mmol) is suspended in acetonitrile (7 ml) and N,N-diisopropyl ethyl amin (1.22 ml; 6.96 mmol) is added at 25 °C. BOP-Q (1.772 g; 6.96 mmol) is added as a solid and after stirring for 30 min at 25°C 4-chloroaniline (0.444 g; 3.48 mmol) is added to the reaction mixture. The mixture is stirred for 18 h at 25°C, evaporated to dryness and dissolved in ethyl acetate (100 ml). The organic phase is washed with with saturated aquous Na2CO3 solution (100 ml), 2 N HC1 (50 ml), water and brine and dried over Na2SC>4, The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography Yield: 0.5 g (36.2 %), ESI-MS: m/z = 395 [M-H]", Cl-pattern Step 3: (3R,4R)-4-(4^Chloro-phe?iylcarbamoyl)-pyrrolidine-3-carboxylic acid ethyl ester hydrochloride 39c Compound 39b (1.6 g; 4.03 mmol) is dissolved in 6N HQ in isopropanol (12.5 ml) and the reaction mixture is stirred for 2 h at 25°C. The reaction mixture is evaporated to dryness and the crude product is crystallized twice from diethylether to yield an off-white solid. Yield: 1.44 g (107.2 %), ESI-MS: m/z = 297 [M+H]+, Cl-Pattern Step 4: (3RAR)-4-(4-Chloro-phehylcarbamdyl)-l-methanesulfonyl-p)n^ carboxylic add ethyl ester 39d Compound 39c (1.44 g; 4.32 mmol) is dissolved in acetonitrile (10 ml) under addition of N,N-diisopropyl ethyl amine (2200 jxl; 12.96 mmol). Methanesulfonylchloride (990 mg; 8.64 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with silica gel chromatography Yield: 0.895 g (55.3 %), ESI-MS: m/z = 375 [M+H]+, Cl-pattern Step 5: (3Ri4R)-4'(4'Chloro'phenylcarbamoyiyi-methanesulfonyl'pyn^ carboxylic add 39e Compound 39d (0.9 g; 2.4 mmol) is dissolved in a mixture of 1,4-dioxane/water (1:1; 15 ml). LiOH monohydxate (0.302 g; 7.2 mmol) is added as a solid and the mixture is stirred for 18 at 25 °C. The mixture is evaporated to dryness and dissolved in ethyl acetate and the product is extracted with saturated aqueous Na2CC>3 solution. The aqueous phase is cooled to 10 °C and acidified with 25% aqueous HCl solution until pH = 1. The product is extracted several times with ethylacetate (3 x 100 ml). The combined organic phases are washed with brine and dried over Na^SO*. After filtration the organic phase is evaporated to dryness. Yield: 0.7 g (84.1 %), ESI-MS: m/z = 345 [M-H]", Cl-pattern Step 6: l~(4~Amino-3~fluoro-phenyl)~3-methox)>-lH-p)nidin-2~one 39f Compound 40f is prepared as described for compound le. ESI-MS: m/z = 345 [M-H]- Step 7: (3R,4R)-l-Metha7iesulfonyl-p)rrolidine-3}4~dicarboxylic acid 3~[(4-chloro-phenyl)-amide] 4'{[2-fluorO'4-(3'methoxy-2-oxO'2H'pyridm'l'yl)'phenyl]'amide} 39g Compound 39e (80 mg; 0.23 mmol) is suspended in acetonitrile (1 ml) and N,N-diisopropyl ethyl amin (47 jil; 0.277 mmol) is added at 25 °C. BOP-C1 (70.5 mg; 0.277 mmol) is added as a solid and after stirring for 30 min at 25°C l-(4-amino-3-fluoro-phenyl)-3-methoxy-lH-pyridin-2-one (53.9 mg; 0.23 mmol) is added to the reaction mixture. The mixture is stirred for 3 d at 25°C, evaporated to dryness and purified by preparative HPLG Yield: 1.9 mg (1.5 %), ESI-MS: m/z = 562 [M+H]+ Example 40 (3R,4R)-l-Metiianestilfonyl-pyrrolidine-3>4-dicarboxylic acid 3-[(4-chloro phenyl)-amide] 4-{[2,6-difluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 40 and l-(4-Amino-375-difluoro-phenyl)-3-methoxy-lH-pyridin-2-one were prepared according to the methods described for example 39. ESI-MS: xn/z = 550 [M+H]+ Example 41 (3R>4R)-1 -Methanesulfonyl-pyrrolidine-S^-dicafboxylic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(6-oxo-6H-pyridazin-1 -yl)-phenyl]-amide} The compound of example 41 and 2"(4-amino-3-fluoro-phenyl)-2H-pyridazin-3-one were prepared according to the methods described for example 39. ESI-MS: m/z = 533[M+H]+ Example 42 (3R,4R)- l-Methanesulfonyl-pyrrolidine-S^-dicarboxylic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fIuoro-4-(2-oxo-piperidin-l-yl)-phenyl]-amide} The compound of example 42 and l-(4-atnino-3-fluoro-phenyl)-piperidin-2-one were prepared according to the methods described for example 39. ESI-MS: m/z = 536 [M+H]+, Cl-pattern Example 43 (3R,4R)-l-Metiianesiilfon7l-pyrroHdine-3)4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-[(3-fluoro-4-morpholin-4-yl-phenyi)-amide] The compound of example 43 was prepared according to the methods described for example 39. 3-fluoro-4-morpholin-4-yl-phenylamine is commercially available. ESI-MS: m/z = 525 [M+H]+, Cl-pattern Example 44 (3R,4R)-l-Methanesulfonyl-pyrrolidine-3)4-dicarbox)rlic acid 3-[(4-chloro~ phenyi)-amide] 4-{[3-fluoro-4"(2-methyl-imidazol-l-yl)-phenyl]-amide} The compound of example 44 and 3-fluoro-4-(2-methyl-imidazol-l-yl)-phenylamine (CAS 209960-27-0) were prepared according to the methods described for example 39. ESI-MS: m/z = 519 [M+H]+, Cl-pattern Example 45 (3R,4R)- l-Methanesulfonyl-pyrrolidine-354-dicarboxylic acid 3- [ (4-chloro-phenyl)-amide] 4-[(3-£luoro-4- [ 1,2,4]triazol-1 -yl-phenyl)-hydroxy-amide] The compound of example 45 was prepared according to the methods described for example 39. N-(3-Fluoro-4-[l>2)4]triazol-l-yl-phenyl)-hydrox5damine is prepared according to CAS: 181997-13-7. ESI-MS: m/z = 523 [M+H]+> Cl-pattern Example 46 (3R,4R)-l-Methanesulfonyl-pyrrolidine-3>4-dicarboxylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridm-l-yl)-phenyl]-aimde}4^ The compound of example 46 was prepared according to the methods described for example 28. ESI-MS: m/z = 543 [M+Hf Example 47 (3R,4R)-l-Metiianesiilfonyl-pyrrolidine-3)4«dicarbosylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} 4-[(4-trifluoromethoxy-phenyl)-axnide] The compound of example 47 was prepared according to the methods described for example 28. ESI-MS: m/z = 583 [M+Hf Example 48 (SR^^-l-Metianesulfonyl-pyrrolidiae-S^dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(2-oxo-2H-pyridin-l-yl)-phenyi]-amide} The compound of example 48 was prepared according to the methods described for example 40. ESI-MS: m/z = 514 [M+H]+ Example 49 (3R>4R)-l-Cyclopropylmethyl--p^Trolidine-3)4-dicarbox}rlic acid 3-[ (4-chloro-phenyL)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 49 was prepared according to the methods described for example 24. ESI-MS: m/z = 508 [M+H]+ Example 50 (3R,4R)-l-MethanesiiIfonyl-pyrrolidine-3,4-dicarbo2ylic acid 3-[(4~chloro-phenyl)-amide] 4-[(3-fluoro-2!-methylsulfanyl-biphenyl-4-yI)-amide] The compound of example 50 was prepared according to the methods described for example 7 using compound CAS 209732-08-1 as amine. ESI-MS: m/z = 562 [M+H]+ Example 51 (3R>4R)-l-Methanesulfonyl-p}Trolidine-3)4-dicarboxylic acid 3-[(2!-fert-butylsulfamoyl-3-fluoro--biphenyl-4-yl)-ainide] 4- [(4~chloro-phenyl)-amide] The compound of example 51 was prepared according to the methods described for example 7 using CAS 209919-51-7 as amine. ESI-MS: m/z = 651 [M+H]+ Example 52 (3R,4R)-l-Meiiianesulfonyl-pyrroUdine-3,4-dicarboxylic acid 3-[(4-chloro- phenyl)-amide] 4-{[5-(2-ine&anesulfonyl-phenyI)-pyridm-2-yl]-ainide} The compound of example 52 was prepared according to the methods described for example 7 using compound CAS 793650-93-8 as amine. ESI-MS: m/z = 577 [M+H]+ Example 53 (3R,4R)-l-Methanesuifonyi-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(3-methyl-2-oxo-2H-pyridin-l-yl)-phenyI]-amide} The compound of example 53 was prepared according to the methods described for example 7. ESI-MS: m/z = 547 [M+H]+ Example 54 (3R,4R)-l-Metiianesuifon7l-pyrroHdine-3,4-dicarboxyiic acid 3-[(4~chloro-phenyl)-amide] 4-[(3-fluoro-2'-metlianesiilfonyl-biplieiiyi-4-7l)-anude] The compound of example 54 was prepared by oxidation of the compound of example 50. The compound of example 50 (39.53 mg; 0.07 mmol) is dissolved in ethyl acetate (2 ml) at 25 °C. To this solution mCPBA (30.34 mg; 2.5 equivalents) is added slowly and the mixture is stirred at 25 °C for 18 h. Purification with prep. HPLC. Yield: 8.15 mg (19.6%). ESI-MS: m/z = 594 [M+H]+ Example 55 (3R)4R)-3-(5-CMoro-pyridin-2-ylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l> yl)-phenylcarbamoyl]-pyrrolidine-l-carbox5rlic acid tert-butyl ester 2-Chloro-5-aminopyridine (3.258 g; 25 mmol) is dissolved in toluene (100 ml) under argon atmosphere. Within 10 min a solution of AlMe3 in toluene (2N> 12.8 ml) is added slowly. The mixture is stirred for 1 h at 25 °C. Compound 28b (10 g, 21 mmol) is added in one portion and the reaction mixture is heated under reflux for 2h. The obtained yellow suspension is cooled to 25 °C and diluted with THF (35 ml). For hydrolysis acetic acid (4.8 ml) is added and the suspension is stirred for 18 h. The obtained precipitate is filtered off, washed with toluene and TBME and dried in vacuo. Yield: 8.46 g (72%). ESI-MS: m/z = 556 [M+H]+ Example 56 (3R>4R)-l«Ethanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin- 2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 56 was prepared according to the methods described for example 7 starting from compound of example 55. ESI-MS: m/z = 547 [M+H] + Example 57 (3R)4R)-l-(2>2-Difluoroeth7l)-p)rrrolidine-3>4-dicarbo^lic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4~(2-oxo-2H-pyridin-l-yl)-phenyl]-ainide} The compound of example 57 is prepared according to the methods described for example 24 with the exception of step 3 and step 4: Step 3: (3R,4R)-pyrrolidine-334-dicarboxylic acid 3-[(5-chlorop)nidin-2-yl)-amide] 4~ {[2-fluoro-4~(2~oxo-2H-pyridin-l-yl)-phenyl]-amide} (compound 57a) The compound of example 55 (8.4 g; 15 mmol) is suspended in dioxane (50 ml) and 4N HC1 in dioxane is added (50 ml). After stirring at 25 °C for 50 min Boc-deavage is completed. The mixture is diluted with THF and neutralized with aqueous Na2CO3-solution. The free base (3R,4R)-p}aroBdine-3,4-dicarboxylic acid 3-[(5-chloropyxidin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyi]-amide} is extracted several times with THF/dichloroxnethane (1:1 vol). The organic phase is washed with saturated aqueous NaCl-solution> dried over Na2SO4 and evaporated to dryness to yield 4.1 g (59.5 %) of compound 57a. ESI-MS: m/z = ■ 455[M+H]+ Step 4: (3R}4R)'l'(2>2-Difluoroethyl)'p}rrolidiii€-3>4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4- {[2-fluoro-4- (2-oxo~2H-pyridin-1 -yl)-phenyl]-amide} Compound 57a (0.41 g; 0.9 mmol) is dissolved in dichloromethane (4 ml) and DIEA (0.233 ml) is added. To this mixture trifluoro-methanesulfonic acid 2>2-difluoro-ethyl ester (0.338 mg; 1.6 mmol), dissolved in 1 ml dichloromethane, is added in one portion. The mixture is stirred at 25 °C for 72 h. The organic phase is then washed with aqueous ammonium acetate and NaCl solution, dried over Na2SO4 and evaporated to dryness. The crude product is purified by flash chromatography over SiO2- Yield: 0.299 g (63.8 %). ESI-MS: m/z = 519 [M+H]+ Example 58 (3R,4R)-l-Methanesulfonyl-pyrrolidine-3?4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(l,l-dioxo-[l,2]thia2inan-2-yl)-phenyl]-ainide} The compound of example 58 was prepared according to the methods described for example 7 with the amine CAS 37441-49-9. ESI-MS: m/z = 555 [M-f-H]+ Example 59 (3R,4R)-l-MethanesiilfonyI-pyrroUdiiie-3,4-dicarbox7lic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-( 1 >l-dioxo-isothiazolidin-2-yI)-phenyI]-amide} The compound of example 59 was prepared according to the methods described for example 7 with the amine CAS 90556-91-5. ESI-MS: m/z = 541 [M-hH]+ Example 60 (3R,4R)-l-MetiiaBesulfonyl-pyrroHdine-34-dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{[2-methyl-4-(2-oxo-2H-pyridin-l~yl)-phenyl]-amide} The compound of example 60 was prepared according to the methods described for example 7 with the amine, l-(4-amino-3-methyl-phenyl)-lH-pyridin-2-one. ESI-MS: m/z = 529 [M+H]+ Example 61 (3R>4R)-l-MetiianesxiIfonyl-pyrrolidine-3>4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fiuoro-4-(3-oxo-morphoIin-4-yl)-phenyl]-amide} The compound of example 61 was prepared according to the methods described for example 7 with CAS 742073-22-9. ESI-MS: m/z = 539 [M+H]+ Example 62 (3R>4R)-l-Isopropyl-pyrrolidine-3)4-dicarboxyIic acid 3-[(5-dJoro-pyridin-2-yl)-amide] 4- {[2-fluoro-4- (2-oxo-2H-pyridin-1 -yl)-phenyl] - amide} The compound of example 62 was prepared according to the methods described for example 27. ESI-MS: m/z = 498 [M+H]+ Example 63 (3R,4R)-l-(4-Fluoro-benzyl)»pyrrolidine-3)4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2If-pyridin-l-yl)-phenyI]-amide} The compound of example 63 was prepared according to the methods described for example 27. ESI-MS: m/z = 563 [M+H]+ Example 64 (3R54R)-l-Metianesulfonyl-pyrroHdine«354-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-[(2-oxO"2H-[l,3!3bipyridinyl»6T-yl)-amide] The compound of example 64 was prepared according to the methods described for example 7 with the amine CAS 536747-63-4. ESI-MS: m/z = 516 [M+H]+ Example 65 (3R,4R)-l-Pyridin-2-ylmetiiyl-pyrrolidine-3,4-dicaTboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 65 was prepared according to the methods described for example 27. ESI-MS: m/z = 546 [M+H]+ Example 66 (S^^-l-Pyridin-S-ylmethyl-pyrroHdine-Sj^dicarboxyiic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyi]-amide} The compound of example 66 was prepared according to the methods described for example 27. ESI-MS: m/z = 546 [M+H]+ Example 67 (3R,4R)-l-Pyridin-4-ylinethyl-pyrrolidine-3,4"dicarboxylic acid 3-[(4-chloro- phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridiii-l-yI)-phenyl]-amide} The compound of example 67 was prepared according to the methods described for example 27. ESI-MS: m/z = 546 [M+H]+ Example 68 (3R,4R)-l-(2-Methoxy-ethyI)-pyrrolidine-3,4-dicarboxyKc acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 68 was prepared according to the methods described for example 24. ESI-MS: m/z = 513 [M+H]+ Example 69 (3R,4R)"l-(2-Fluoro-l-methyl-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H»pyridin-l-yl)-phenyl]-amide} The compound of example 69 was prepared according to the methods described for example 27. ESI-MS: m/z = 515 [M+H]+ Example 70 3-{(3R)4R)-3-(4-CUoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidin-l-yl}-propionic acid methyl ester The compound of example 70 was prepared according to the methods described for example 24. ESI-MS: m/z = 541 [M+H]+ Example 71 (3R>4R)-l-(3-Huoro-oxeten-3*ylme1^yi)-pyrrolidine-3,4-dicarbox7lic acid 3-[(4-chioro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2ii-pyridin-l~yl)-pherxyI]-ainide} The compound of example 71 was prepared according to the methods described for example 24 using 3-bromomethyl-3-fluoro-oxetane (compound 71 e) as alkylating agent ESI-MS: m/z = 543 [M+H]+ Synthesis of3-bromomethyl-3-fluoro-oxetane: a) 3-Benz)4oxy-2-methylene-l-propanol 71a: 2-Methylene-propane-l>3-diol (2.2 g; 24.96 nunol)and dibutyltin oxide (6.85 g; 27.96 mmol) were refluxed in chloroform/ methanol (100 ml 10:1) for 24 h to obtain a clear solution. The solvent was removed under reduced pressure to give the starmoxane derivative as a white solid. Cesium fluoride (7.25 g; 47.7 mmol) was added and the mixture was dried under high vacuum. To this reaction mixture, DMF (20 ml) and benzyl bromide (3.27 ml; 27.5 mmol) were added and the reaction mixture was stirred for 24 h at 25 °C. After that, the reaction mixture was heated at 50 °C for 1 h. The mixture is cooled to 25 °C and diluted with ethyl acetate (100 ml) and water (2 ml). The reaction mixture is stirred vigorously for 30 min and then filtered through a pad of celite to remove dibutyltin oxide. The filtrate was washed with water and then with brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography eluting with 20 % ethyl acetate/hexane to yield 2.6 g (60%) compound 71a) as oil. *H-NMR (CDC13): 5 7.36 - 7.28 (m, 5H)> 5.20 (s, 1H), 5.15 (s, 1H)> 4.51 (s, 2H), 4.19 (s,2H), 4.10 (s,2H). b) 3-Bromo-2-fluoro-2-(ben2yloxymethyl)propan-l-ol 71 b: A solution of 71 a) (3.9 g; 21.91 mmol) and triethylamine 3HF complex (5.29 g; 5.35 ml; 32.86 mmol) in dichloromethane (100 ml) was treated with NBS (4.28 g; 24.1 mmol) portion wise at -10 °C and stirred for 17 h. Subsequently the mixture was poured into ice-water (100 ml) and neutralized with 25% aqueous ammonia. The organic layer was separated, washed with 0.1 N HC1, followed by 5 % aqueous NaHCO3, dried and evaporated to dryness. The crude material was purified by silica gel chromatography (15 % ethyl acetate/hexane) to give 2.54 g (42%) of 71 b. :H-NMR (CDC13): 5 7.37 - 7.30 (m, 5H), 4.58 (s, 2H), 3.89 - 3.63 (m, 6H), GC~ MS: 276 (M*). c) 3-Fluoro-3-(benzyloxymethyl)oxetane 71 c: A mixture of 71 b (10 g; 36.10 mmol) and potassium carbonate (29.9 g; 216.9 mmol)) in dry acetonitrile (200 ml) is refluxed for 72 h. After that the reaction mixture is extracted with ethyl acetate, washed with brine, dried over Na2SC>4 and purified by silica gel column chromatography (10% ethyl acetate/hexane) to give 2.12 g (30%) of 71c. *H-NMR (CDCU): 6 7.38 - 7.30 (m, 5H), 4.77 (dd> 2H), 458 (dd, 2H), 3.81 (s, 1H), 3.76 (s, 1H), GC-MS: 196 (M+). d) 3-Fluoro-3-(hydroxymethyl)oxetane 71 d: A solution of 71 c (1.1 g; 5.61 mmol) in EtOH (10 ml) containing Pd/C (200 mg, 10%) and acetic acid (1 ml) was stirred for 24 h under hydrogen atmosphere (40 psi). The catalyst was filtered off and the filtrate was concentrated under reduced pressure to give compound 71 d (410 mg; 70%). ^-NMR (CDC13): 5 4.77 (dd, 2H), 4.57 (dd, 2H), 3.98 (s, 1H), 3.93 (s, 1H). e) 3-Bromomethyl~3-fluoro-oxetane 71 e: To a stirred solution of compound 71 d (500 mg; 4.72 mmol) CBr4 (1.95 g; 5.89 mmol) in dichloromethane (7 ml) was added portion "wise triphenylphosphine (1.85 g; 7.07 mmol) at 0 °C. After complete addition, the reaction mixture was stirred for additional 2 h, diluted with pentane and washed with 5% aq NaHCO3, brine and dried over Na2SC>4 .The solvent was removed under atmospheric pressure to give compound 71 e (406 mg, 51%). aH-NMR (CDCI3): 6 4.79 (dd, 2H), 4.56 (dd, 2H), 3.78 (s, 1H), 3.73 (s, 1H). Example 72 2-{(3R,4R)-3-(4'CUoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrroUdin-l-ylmethyl}-cyclopropanecarboxylic acid ethyl ester The compound of example 72 was prepared according to the methods described for example 24. ESI-MS: m/z = 581 [M+H]+ Example 73 (3R34R)-l-Thiophen-2-yimethyl-pyrrolidine-3,4-dicarboxyiic acid 3- [(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yI)-phenyl]-amide} The compound of example 73 was prepared according to the methods described for example 27. ESI-MS: m/z = 551 [M+H]+ Example 74 (3R,4R)-l-TMophen-3-ylme^ acid 3-[(4-chloro- phenyl)-amide] 4- {[2~fluoro-4-(2-oxo-2i?-pyridin-1 -yl)-phenyl] -amide} The compound of example 74 was prepared according to the methods described for example 27. ESI-MS: m/z = 551 [M+H]+ Example 75 (3R,4R)-l-Cyanomethy]-pyrrolidine-3?4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo"2H-p^idin-l-yl)"phenyl]-amide} The compound of example 75 was prepared according to the methods described for example 24. ESI-MS: m/z = 494 [M+H]+ Example 76 (3R,4R)-l-Metiiyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-methyl-amide] 4*{[2-fluoro*4-(2-oxo-2H-pyridin-l-yl)-phenyl]-methyl-amide} The compound of example 76 was prepared according to the methods described for example 24. ESI-MS: m/z = 494 [M-f H]+ Example 77 (3R,4R)-l-(2-Tetra^ol-l-yl-acetyI)-pyrrolidine-3,4-dicarboxylic acid 3-[(4-diloro-phenyI)-amide]4-{[2'fluoro-4-(2-oxo-2iJ-pyridin-l-yl)-phenyl]-ainide} The compound of example 77 was prepared according to the methods-described for example 13. ESI-MS: m/z = 565 [M+H]+ Example 78 (3RJ4R)-l-(2-lH-Tetrazol-5"yl-acetyl)-pyrrolidine-3,4-dicarbo^Uc acid 3-[(4-chloro-phenyl) - amide] 4- {[2-fluoro-4- (2-oxo-2H-pyridin-1 -yl) -phenyl] - amide} The compound of example 78 was prepared according to the methods described for example 13. ESI-MS: m/z = 565 [M+H]+ Example 79 (3R,4R)-l-(2,2-Difluoro-ethyI)«pyrroIidine-3,4-dicarboxylic acid 3-[(6-chloro-pyridazin-3-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2i?-pyridin-l-yl)-phenyl]-amide} The compound of example 79 was prepared according to the methods described for example 57. ESI-MS: m/z = 521 [M-f-H]+ Example 80 (3R>4R)-l-(2,2-Difluoro-etiy])-pyrrolidine»3,4-dicarboxylic acid 3-[(5-chloro-pyrimidin-2-yI)-amide] 4-{[2-fIuoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 80 was prepared according to the methods described for example 57. ESI-MS: m/z = 521 [M+H]+ Example 81 (3R54R)-l-(2,2-Difluoro-eth7l).pyrrolidine-3,4-dicarbox^Kc acid 3-[(5-chIoro-thiophen-2-yL)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 81 was prepared according to the methods described for example 57. ESI-MS: m/z = 525 [M+H]+ Example 82 (3R,4R)-l-Methanesidfon)i-pyn-olidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyi)-amide] 4-{ [4-{3-oxo-moi^holin-4-yl)-phenyl] -amide} The compound of example 82 was prepared according to the methods described for example 7 using as amine CAS 438056-69-0. ESI-MS: m/z = 521 [M+H]+ Example 83 (3R>4R)*3-(5-CWoro-pyridin-2-ylcarbamoyl)-4"[2-fluoro-4-(2-oxo-2H-pyridiii-l-yl)-phenylcafbamoyl]-pyrrolidine-l-carboxylic add methyl ester The compound of example 83 was prepared according to the methods described for example 57 and 14. ESI-MS: m/z = 514 [M+H]+ Example 84 (3R,4R)-l-Trifluoromethyl-pyrrolidine-3)4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 84 was prepared according to the methods described for example 57. ESI-MS: m/z = 524 [M+H]+ Example 85 (3R,4R)-l-(2>2,2-Trifluoro-ethyl)-p}Trolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-aniide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin"l-yl)-phenyl]-amide} The compound of example 85 was prepared according to the methods described for example 57. ESI-MS: m/z = 538 [M+H]+ Example A Film coated tablets containing the following ingredients can be manufactured in a conventional manner: Ingredients Per tablet Kernel: Compound of formula (I) 10.0 mg 200.0 mg Microcrystalline cellulose 23.5 mg 43.5 mg Lactose hydrous 60.0 mg 70.0 mg Povidone K30 12.5 mg 15.0 mg Sodium starch glycolate 12.5 mg 17.0 mg Magnesium stearate 1.5 mg 4.5 mg (Kernel Weight) 120.0 mg 350.0 mg Film Coat Hydroxypropyl methyl cellulose 3.5 mg 7.0 mg Polyethylene glycol 6000 0.8 mg 1.6 mg Talc 1.3 mg 2.6 mg Iron oxyde (yellow) 0.8 mg 1.6 mg Titan dioxide 0.8 mg 1.6 mg The active ingredient is sieved and mixed with rnicrocristalline cellulose and the mixture is granulated with a solution of polyvinylpyrrolidon in water. The granulate is mixed with sodium starch glycolate and magesiumstearate and compressed to yield kernels of 120 or 350 mg respectively. The kernels are lacquered with an aqueous solution / suspension of the above mentioned film coat. Example B Capsules containing the following ingredients can be manufactured in a conventional manner: Ingredients Per capsule Compound of formula (I) 25.0 mg Lactose 150.0 mg Maize starch 20.0 mg Talc 5.0 mg The components are sieved and mixed and filled into capsules of size 2. Example C Injection solutions can have the following composition: Compound of formula (I) 3.0 mg Polyethylene Glycol 400 150.0 mg Acetic Acid - ■ q.s. ad pH 5.0 Water for injection solutions ad 1.0 ml The active ingredient is dissolved in a mixture of Polyethylene Glycol 400 and water for injection (part). The pH is adjusted to 5.0 by Acetic Acid. The volume is adjusted to 1.0 ml by addition of the residual amount of water. The solution is filtered, filled into vials using an appropriate overage and sterilized. Example D Soft gelatin capsules containing the following ingredients can be manufactured in a conventional manner: Capsule contents Compound of formula (I) 5.0 mg Yellow wax 8.0 mg Hydrogenated Soya bean oil 8.0 mg Partially hydrogenated plant oils 34.0 mg Soya bean oil 110.0 mg Weight of capsule contents 165.0 mg Gelatin capsule Gelatin 75.0 mg Glycerol 85 % 32.0 mg Karion 83 8.0 mg (dry matter) Titan dioxide 0.4 mg Iron oxide yellow 1.1 mg The active ingredient is dissolved in a warm melting of the other ingredients and the mixture is filled into soft gelatin capsules of appropriate size. The filled soft gelatin capsules are treated according to the usual procedures. Example E Sachets containing the following ingredients can be manufactured in a conventional manner: Compound of formula (I) 50.0 mg Lactose, fine powder 1015.0 mg Microcristalline cellulose (AVICEL PH 102) 1400.0 mg Sodium cafboxymethyl cellulose 14.0 mg Polyvinylpyrrolidon K 30 10.0 mg Magnesiumstearate 10.0 mg Flavoring additives 1.0 mg The active ingredient is mixed with lactose, microcristalline cellulose and sodium carboxymethyl cellulose and granulated "with a mixture of polyvinylpyrrolidon in water. The granulate is mixed with magnesiumstearate and the flavouring additives and filled into sachets. Novel pyrroIidiDe-3,4"dicarboxamide derivatives The invention is concerned with novel pyrroKdme-3>4-dicarboxamide derivatives of the formula (I) wherein X is N or C-R6; R1 is hydrogen, lower-alkyl, cycloalkyl> cydoalkyHower-alkyl, fhioro-lower-alkyl> hydroxy-lower-alkyl, CN-lower-alkyl, hydroxy substituted fluoro-lower-alkyl, lower-alkinyl, R10C(O)-, R10OC(O)-, N(R11,R12)C(O)-> R10OC(O)-lower-al3cyl3 N(Ra>R12)C(O)4ower-alkyl, R10-SO2, R10-SO2-lower-alkyl, NCR11^12)^©,, N(Ru,R12)-SO2-lower-alkyl? aryi-lower-alkyi, heteroaryl, heteroaryi-lower-alkyl, lower alkoxy-lower aDq^i, lower alkoxycarbonyl-cycloalk)d-lower aBcyl or heteroq^clyl-lower alkyl; R is hydrogen or lower-alkyl; R is aryl, aryl-lower-alkyl, heteroar}d or heteroaryl-lower-alkyl; R4 is hydrogen, lower-alkyl or hydroxy; R53 R55 R7 and R8 independently from each other are selected from the group consisting of hydrogen^ halogen, lower-alkyl, lower-alkoxy, fiuoro-lower-alkyl, fluoro-lower-alkyloxy or CN; R9 is aryl, heterocyclyl, heteroaryl or heterocyclyl-C(O)-; R is hydrogen, lower-allcyl, cydoalkyl, cydoalkyl-lower-alkyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-arkyl-SO2-lower-alkyl, aryl, aryl-lower-alkyl, heteroaryl/heteroaryl-lower-alkyl or heterocydyl; R and R independently from eadi other are sdected from the group consisting of hydrogen, lower-allcyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, cydoalkyi, cydoalkyl-lower-alkyl, aryl, aryl-lower-alkyl, heteroaryl and heteroaryl-lower-alkyl; or Ru and R12, together with the nitrogen atom to whidi they are attached, form a heterocydic ring selected from the group consisting of piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl, pyrrolinyl or azetidinyl, which heterocydic ring can optionally be substituted with lower-alkyl, halogen or hydroxy; and pharrnaceutically acceptable salts thereof. Further, the invention is concerned with a process for the manufacture of the above compounds, pharmaceutical preparations which contain such compounds as well as the use of these compounds for the production of pharmaceutical preparations. The compounds of formula (I) are active compounds and inhibit the coagulation factor Xa. These compounds consequently influence blood coagulation. They therefore inhibit the formation of thrombi and can be used for the treatment and/or prevention of thrombotic disorders, such as amongst others, arterial and venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease (PAOD), unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke (cerebral thrombosis) due to atrial fibrillation, inflammation and arteriosclerosis. They have potentially benefit in the treatment of acute vessel closure associated with thrombolytic therapy and restenosis, e.g. after transluminal coronary angioplasty (PTCA) or bypass grafting of the coronary or peripheral arteries and in the maintenance of vascular access patency in long term hemodialysis patients. F.Xa inhibitors of this invention may form part of a combination therapy with an anticoagulant with a different mode of action or with a platelet aggregation inhibitor or with a thrombolytic agent. Furthermore, these compounds have an effect on tumour cells and prevent metastases. They can therefore also be used as antitumour agents. Other inhibitors of factor Xa, which are not structurally related to the compounds of the present invention, had previously been suggested for the inhibition of the formation of thrombi and for the treatment of related diseases (WO 03/045912). However, there is still a need for novel factor Xa inhibitors which exhibit improved pharmacological properties, e.g. an improved selectivity towards coagulation factor Xa. The present invention provides the novel compounds of formula (I) which are factor Xa inhibitors The compounds of the present invention unexpectedly inhibit coagulation factor Xa and also exhibit unproved pharmacological properties compared to other compounds already known in the art. Unless otherwise indicated, the following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein. In this specification the term "lower" is used to mean a group consisting of one to seven, preferably of one to four carbon atom(s). The term £Chalogen" refers to fluorine, chlorine, bromine and iodine, with fluorine, chlorine and bromine being preferred. The term "alky!", alone or in combination with other groups, refers to a branched or straight-chain monovalent saturated aliphatic hydrocarbon radical of one to twenty carbon atoms> preferably one to sixteen carbon atoms, more preferably one to ten carbon atoms. Lower-alkyl groups as described below also are preferred alkyl groups. The term "lower- alkyPj alone or in combination with other groups, refers to a branched or straight-chain monovalent alkyl radical of one to seven carbon atoms, preferably one to four carbon atoms. This term is further exemplified by such radicals as methyl, ethyl, n-propyl, isopropyl, n-butyl, i-butyl, t-butyl. Lower-alkyl groups can optionally be substituted, e.g, by hydroxy or CN. Such substituted lower-alkyl-groups are referred to as "hydroxy-lower-alkyl" or "CN-lower-alkyl" respectively. Other possible optional substituents are e.g. halogen. Unsubstituted lower-alkyl groups are preferred. The term "fluoro-lower-alkyl" refers to lower-allcyl groups which are mono-or multiply substituted with fluorine. Examples of fluoro-lower-alkyl groups are e.g. CFH2, CF2H3 CF3, CF3CH2, CF3(CH2)2, (CF3)2CH and CF2H-CF2. The term "cycloalkyT refers to a monovalent carbocyclic radical of 3 to 10 carbon atoms, preferably 3 to 6 carbon atoms, such as cyclopropyl, cydobutyl, cyclopentyl, or cydohexyl. The term "alkoxy" refers to the group R3-O-> wherein RJ is an alkyi. The term 'lower-alkoxy* refers to the group R'-O-, wherein R' is a lower-aBcyL The term "thio-alkoxy" refers to the group R'-S-, wherein R' is an alkyl. The term "thio-lower-alkoxy" refers to the group R'-S-, wherein R* is a lower-alkyL The term "fluoro-lower-alkoxy" refers to the group R"-O-, wherein R" is fluoro-lower-alkyl. Examples of fluoro-lower-alkoxy groups are e.g. CFH2-O, CF2H-O, CF3-O, CF3CH2-O, CF3(CH2)2-O, (CF3)2CH-O, and CF2H-CF2-O. The term "alkenyT, alone or in combination with other groups, stands for a straight-chain or branched hydrocarbon residue comprising an olefinic bond and 2 to 20, preferably 2 to 16 carbon atoms, more preferably 2 to 10 carbon atoms. Lower-alkenyl groups as described below also are preferred alkenyl groups. The term 'lower-alkenyT refers to a straight-chain or branched hydrocarbon residue comprising an olefinic bond and 2 to 7, preferably 2 to 4 carbon atoms, such as e.g. 2-propenyL The term "alkinyl", alone or in combination with other groups, stands for a straight-chain or branched hydrocarbon residue comprising a tripple bond and up to 20, preferably up to 16 carbon atoms. The term "lower-alkinyl" refers to a straight-chain or branched hydrocarbon residue comprising a tripple bond and 2 to 7, preferably 2 to 4 carbon atoms, such as e.g. 2-propinyl. Lower-alkinyl groups can be substitutedj e.g. by hydroxy. The term "alkylene" refers to a straight chain or branched divalent saturated aliphatic hydrocarbon group of 1 to 20 carbon atoms, preferably 1 to 16 carbon atoms, more preferably up to 10 carbon atoms. Lower-alkylene groups as described below also are preferred alkylene groups. The term "lower-alkylene" refers to a straight chain or branched divalent saturated aliphatic hydrocarbon group of 1 to 7, preferably i to 6 or 3 to 6 carbon atoms. Straight chain alkylene or lower-allryiene groups are preferred. The term "aryl" relates to the phenyl or naphthyl group> preferably the phenyl group, which can optionally be substituted by 1 to 5 , preferably 1 to 3, substituents independently selected from the group consisting of lower-alkenyl, lower-alkinyl, dioxo-lower-alkylene (forming e.g. a benzodioxyl group), halogen, hydroxy, CN, CF3, NH2, N(H, lower-alkyl), N(lower-alkyl)2, aminocarbonyl, carboxy, NO2, lower-alkoxy, thio-lower-alkoxy, lower-alkylsufonyl, aminosulfonyl, lower-alkylcarbonyl, lower-alkylcarbonyloxy, lower-alkoxycarbonyl, lower-alkyl-carbonyl-NH, fluoro-lower-alkyl, fluoro-lower-alkoxy, lower-alkoxy-carbonyl-lower-alkoxy, cafboxy-lower-alkoxy, carbamoyl-lower-alkoxy, hydroxy-lower-alkoxy, NH2-lower-alkoxy, N(H, lower-alky^-lower-alkoxy, N (lower-alkyl)2-lower' alkoxy, benzyloxy-lower-alkoxy, mono- or di-lower alkyl substituted amino-sulfonyl and lower-alkyl which can optionally be substituted with halogen, hydroxy, NH2> N(H, lower-alkyl) or N(lower-alkyl)2? preferably selected from the group consisting of lower-alkenyi, lower-alkinyl, dioxo-lower-alkylene (forming e.g. a benzodioxyl group), halogen, hydroxy, CN, CF3> NH2, N(H> lower-alkyl), N(lower-alkyl)2> aminocarbonyl, carboxy, NO2> lower-alkoxy, thio-loM^er-alkoxy, lower-alkylsufonyl, aminosulfonyl, lower-alkylcarbonyl, lower-alkylcarbonyloxy, lower-alkoxycarbonyl, lower-alkyl-cafbonyl-NH5 fluoro-lower-alkyl, fluoro-lower-alkoxy, lower-alkoxy-carbonyl-lower-alkoxy, carboxy-lower-alkoxy, carbamoyl-lower-alkoxy, hydroxy-lower-alkoxy, NH2-lower-a]koxy, N(H, lower-alkyl)-lower-alkoxy, N(lower-alkyl)2-lower-alkoxy, benzyloxy-lower-alkoxy and, lower-alkyl which can optionally be substituted with halogen, hydroxy, NH2> N(H, lower-alkyl) or N(lower-alkyl)2.. Preferred substituents are halogen, lower-alkoxy, fluoro-lower-alkoxy, thio-lower-alkoxy, and amino. The term "heterocydyT as used herein denotes non-aromatic monocyclic heterocycles with 4 or 6 ring members, which comprise 1, 2 or 3 hetero atoms selected from nitrogen, oxygen and sulfur. A hetero atom can be -SO- or -SO2-. Examples of suitable heterocycles are pyrrolidinyl, oxopyrrolidinyl, isoxazolidinyl, isoxazolinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, 2-oxo-piperidinyl, 3-oxo-morpholinyl, 2-oxo-piperazinyl, 2-oxo-oxazolidinyl, 2-oxo-azetidinyl, piperazinyl, morpholinyl, pyranyl, tetrahydrop'jTranyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-thiazolyl. Preferred heterocydes are, morpholinyl, 3-oxo-morpholinyl, 2-oxo-piperazinyl and 2-oxo-piperidinyl. A heterocyclyl group may have a substitution pattern as described earlier in connection with the term "aryl". One or two ring member carbon atoms of a heterocyclyl group maybe replaced with a carbonyl group. The term "heteroaryl" refers to an aromatic 5 to 6 membered monocyclic ring or 9 to 10 membered bicyclic ring which can comprise 1,2, 3 or 4> preferably 1, 2 or 3 atoms selected from nitrogen, oxygen and/or sulphur, such as foryl, pyridyl, pyridazinyl, oxo-pyridazinyl, pyrimidinyl, 2-oxo-pyridinyl, 2-oxo-pyrimidinyl pyrazinyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1,2,3-thiadiazolyl, benzoimidazolyl, indolyl, indazolyl, Preferred heteroaryl groups are 2-oxo-pyridinyL, 2-oxo-pyrimidinyl, pyridinyl, and indolyl. A heteroaryl group may have a substitution pattern as described earlier in connection with the term "aryT. Preferred substituents are halogen, lower-alkyl, lower-alkoxy or CN. One or two ring member carbon atoms of a heteroaryl group maybe replaced with a carbonyl group. The term "mono-lower alkyl substituted amino" and "di-lower alkyl substituted amino* refer to -NHR and -NRR5 respectively, wherein R and RJ independent from each other are lower alkyl. Preferred radicals for the chemical groups whose definitions are given above axe those specifically exemplified in Examples. Compounds of formula (I) can form pharmaceutically acceptable acid addition salts. Examples of such pharmaceutically acceptable salts are salts of compounds of formula (I) with physiologically compatible mineral acids, such as hydrochloric add, sulphuric add, sulphurous add or phosphoric add; or with organic adds, such as methanesulphonic acid, p-toluenesulphonic add, acetic add, lactic add, trifluoroacetic add, citric acid, fumaric acid, maleic acid, tartaric add, succinic add or salicylic add. The term "pharmaceutically acceptable salts" refers to such salts. Compounds of formula (I) in which a COOH group is present can further form salts with bases. Examples of such salts are alkaline, earth-alkaline and ammonium salts such as e.g. Na-, K-, Ca- and Trimethylammoniumsalt The term "pharmaceutically acceptable salts" also refers to such salts. Acid addition salts as described above are preferred. In detail, the present invention relates to compounds of formula (I) X is N or C-R6; R1 is hydrogen, lower-alkyl, cycloalkyl, cycloalkyl-lower-alkyl, fluoro-lower-alkyl, hydroxy-lower-alkyl, CN-lower-alkyl, hydroxy substituted fluoro-lower-alkyl, lower-alkinyl, R10C(O)-, R10OC(O)-, N(Rn,R12)C(O)-, R10OC(OHower-alkyl, N(Ru,R12)C(OHower-aIkyl, R10-SO2, R20-SO2-lower-alkyl, N(R11 J112)-SO2, N(R11 Jl12)-SO2-lower.alkyi, aryl-lower-alkyl, heteroaryi, heteroaryl-lower-alkyl, lower alkoxy-lower alkyl, lower alkoxycarbonyi-q^cloalkyl-lower alkyi or keterocyclyl-lower alkyl; R is hydrogen or lower-alkyl; R is arylj aryl-lower-allcyl, heteroar^'i or heteroaryi-lower-alkyl; R4 is hydrogen, lower-alkyl or hydroxy; R5> R6, R7 and R8 independently from each other are selected from the group consisting of hydrogen, halogen, lower-alkyl, lower-alkoxy, fluoro-lower-alkyl, fluoro-lower-alkyloxy or CN; R9 is arjd, heterocyclyl, heteroaryl or heterocyclyl-C(O)-; R10 is hydrogen, lower-alkyl, cycloalkyl, cycloalkyl-lower-alkyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkyl-SO2-lower-alkyl, aryl, aryl-lower-alkyl, heteroaryl, heteroaryl-lower-alkyl or heterocydyl; Ru and R12 independently from each other are selected from the group consisting of hydrogen, lower-alkyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, cycloalkyl, q^cloalkyl-lower-alkyl, aryl, aryl-lower-alkyl, heteroaryl and heteroaryl-lower-alkyl; or R and R , together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from the group consisting of piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl, pyrrolinyl or azetidinyl, -which heterocyclic ring can optionally be substituted "with lower-alkyl, halogen or hydroxy, and pharmaceuticafly acceptable salts thereof Preferably R1 is hydrogen, lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, fluoro-lower alkyl, hydroxy-lower alkyl, CN-lower alkyl, hydroxy substituted fluoro-lower alkyl, lower alkinyl, R10C(O)-, R10OC(O)^ N(Rn,R12)C(O)-, R10OC(O)-lower alkyl, N(Rn,R12)C(O)-lower alkyl, R10-SO2, R10-SO2-lower alkyl, N(RU5R12)-SO2? N(Rn,R12)-SO2-lower alkyl, ar)i-lower alkyl, heteroaryl or heteroaryl-lower alkyl; R10 is hydrogen, lower alkyl, cydoalkyl, q^doalkyl-lower alkyl, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkyl-SO2-lower alkyl, aryl, aryl-lower alkyl, heteroaryl or heteroaryl-lower alkyl. Compounds of formula (I) are individually preferred and physiologically acceptable salts thereof are individually preferred, with the compounds of formula . (I) being particularly preferred. The compounds of formula (I) have at least two asymmetric C atoms and can therefore exist as an enantiomeric mixture, diastereomeric mixture or as optically pure compounds. Preferred are compounds which are 3R,4R-pyrrolidine-3,4-dicarboxylic acid derivatives. One preferred embodiment of the present invention therefore relates to compounds of formula (I) as defined above, characterised by formula (la) wherein R1, R2, R3, R4, R5> R7, R8, R9 and X are as defined above, and pharmaceutically acceptable salts thereof. Preferred compounds of formula (I) are those, wherein R1 is hydrogen, lower-alkyl, fluoro-lower-alkyl, hydroxy-lower-alkyl, CN-lower-alkyi, HC(O)~, lower-aUcyl-CXO)-, lower-allcoxy-C(O)-? lower-alkoxy-C(O)-lower-aIkyI, NH2-C(O)-lower-alkyl, lower-aIkyl-NH-C(O)-lower-alkyl, NH2-SO2, lower-alkyl-SO2, fluoro-lower-aIkyl-SO2, N(lower-alkyl)2-SO2 or pyrrolidino-C(O)-. Compounds as defined above, wherein R1 is lower-alkyl, fluoro-lower-alkyl, lower-alkyl-SO2) fluoro-lower-alkyl-SO2, N(lower-alkyl)2-SO2, lower-alkoxy-C(O)- or HC(O)-, are more preferred, with those compounds as defined above, wherein R1 is 2,2-difluoro-ethyl, ethanesulfonyl, methanesulfonyl, propylsulfonyl, isopropylsulfonyl, 2,2,2-trifluoro-ethylsulfonyl, isopropyl, N(CH3)2-SO2) ethoxy-carbonyl, or formyl, being particularly preferred. In another preferred embodiment of the present invention, R is hydrogen. Furthermore, compounds as defined above, wherein R is phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, NH2, lower-alkoxy and fluoro-lower-alkoxy, or R is benzyl optionally substituted with halogen, or R is pyridinyl optionally substituted with halogen, or R is indolyl, are preferred. Particularly preferred are those compounds, wherein R is phenyl substituted with halogen or R3 is pyridinyl substituted with halogen. Most preferably, R3 is 4-dbloro-phenyl or 5-chloro-pyridin-2-yl. In a further preferred embodiment of the present invention, R4 is hydrogen. Another preferred embodiment of the present invention relates to compounds of formula (I) as defined above, wherein X is C-R6 and R6 is as defined above. Preferably, X is C-R6 and R5, R6, R7 and R8 independently from each other are selected from the group consisting of hydrogen and halogen. More preferably, X is C-R6, R6 is halogen, R5, R7 and R8 are hydrogen. Most preferably, X is C-R6, R6 is fluorine, R5, R7 and R8 are hydrogen. The invention especially embraces compounds of formula (I) as described above, wherein R9 is aryl, heterocyclyl or heteroaryl. Those compounds, wherein R9 is heteroaryl, are preferred. A preferred heteroaryl group for R9 is one selected from the group consisting of furyl, pyridyl, pyridazinyl, oxo-pyridazinyl, pyrimidinyl, 2-oxo-pyridinyl, 2-oxo-pyrimidinyl pyrazinyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1,2,3-thiadiazolyl, benzoimidazolyl, indolyl and indazolyl. 2-oxo-2H-pyridin-1-yl is particularly preferred. In particular, preferred compounds are the compounds of formula (I) described in the examples as individual compounds as well as pharmaceutically acceptable salts thereof. Preferred compounds of formula (I) are those selected from the group consisting of (3R,4R)-l-(2,2>2-Trifluoro-ethyl)-pyrroHdine-3>4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H«pyridin-l-yl)-phenyl]-ainide}, (3R>4R)-l-(2>2-Difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H»pyridin-l-yl)-phenyl]-amide}, (3R>4R)-l-Sulfamoyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-p37ridin-l-yl)-phenyl] -amide}, (3R,4R)-l-Sulfamoyl-pyrrolidine-3>4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)Tridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Eiianesulfonyl-pyrroHdiiie-3,4-dicarboxylicadd3-[(4-cUoro-^^ amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R,4R)-l-Methanesiilfonyl-pyrrolidine-3,4--dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Isopropyl-pyrroUdine-3,4-dicarboxylicacid3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R>4R)-l-Methanesulfonyl-p')?rrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-p)T:rolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p}rridin-l-yl)-phenyl]-amide}, (3R,4R)-1-Meikylcarbamoylmetk^ add 3-[(4-chloro phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)7ridin-l-yl)*phenyl]-amide}, (31MI0-3-(4-Chloro-phenylca^ phenylcarbamoylj-pyrrolidine-l-cafboxj^lic acid methyl ester, (3R?4R)-l-(2-Hydroxy-ethyl)-pyrrolidine-334-dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H"pyridin-l-yl)-phenyl]-amide}, 1rans-(3RSJ4RS)"l-MethanesulfonyI-pyiToHdine-3)4-dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluorO"4-(2-oxo-2H-pyridin-l-yI)-phenyl]-amide}> (3RJ4R)-l-Met±ianesulfonyl-pyrroHdine-3?4-dicarbox)7iic add 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(3-methox7-2-oxo-2H'pyridin-l-yl)-phenyl] -airu.de}> (3R)4R)-l-Acetyi-pyrrolidine-3,4-dicarboxyiic add 3-[(4-chloro-phenyl)-amide] 4-{[4-(3-methoxy-2-oxo-2H-pyridin-I-yI)-phenyI]-amide}> tTajis-(3RS>4RS)-I-Cyanomethyl-p)Trolidine-3>4-dicarbox7iic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yi)-phenyI]-amide}, txaxis-(3RS4RS)-l-Carbamoyimethyl-p}7rrolidine-3>4"dicarboxylic add 3-[(4-chloro-phenyi)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin*-l-yl)*phenyl]-amide}, trans-CSRS^Sj-l-CS^jS-Trifluoro-propy^-p^olidine-S^-dicarboxyiic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluora-4-(2-oxo-2H-pyridin-l-yl}-p3ienyl]-amide}, (3R)4R)-l-Formyl-pyrrolidine-3,4-dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R>4R)-l-Methanesulfonyl-pyrroUdine-3)4-dicarboxylic add 3-[(4-cbloro-3-fiuoro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)Tidin-l-yl)-phenyl]-amide}} (3R)4R)-l-Meiiianesiilfonyl-pyrroIidine-3J4-dicarboxylLC add 3-[(4-chloro-2-fluoro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p}T:idin-l-yl)-plienyl]-amide}? trans-(3RS,4RS)-{3-(4-Chloro-phenylcarbamoyI)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyi]-p)7rrolidin-l-yl}-acetic add ethyl ester, (3R,4R)-l-Methanesulfon}i-pyrroKdine-3)4-dicarboxylic add 3-[(3-fluoro-4-methoxy-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyi]-ainide}s (3R,4R)-l-Methanesulfonyl-p)7rrolidine-3>4-dicarboxylic add 3-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} 4-[(lH-indol-5-yl)-amide], (3R,4R)-l-Methanesulfonyl-p)7rrolidine-3>4-dicarboxylic add 3-[(2-amino-4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-pyrroHdine-3s4-dicarboxylic add 3-{[2-fluoro-4-(2-oxo-2H-pyridin-1 -yl) -phenyi] - amide} 4- [ (4-methoxy-phenyl) - amide], (3R,4R)-I-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic add 3-[(4-chloro-phenyl)"amide] 4-[(3-fluoro-4-morpholin-4-yl-phenyl)-amide], (3S4S)-l-Methanesidfonyl-pyrrolidine-3>4-dicarbox7lic acid 3-[ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-plienyl]-amide}) (3R,4R)-l-Methanesulfonyl-p-5TTolidine-3>4-dicarboxylic acid 3-[(3-chloro-4-metitioxy-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyi]-ainide}5 (SR^^-l-Metiianesulfonyl-pyrroHdine-S^-dicarboxylic acid 3-[(4-chloro-phenyl)-methyl-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yi)-phenyl]-ainide}, (3R54R)-l-Methanesulfonyl-pyrrolidiiie-354-dicarboxylic acid 3-{ [2-fluoro-4-(2-oxo-2H-pyridin-1 -yl)-phenyl] -amide} 4- [(IH-indazol-5-yl)-amide], (3R>4R)"l-Methanesulfonyl-pyrrolidine-3>4--dicarbox5rlic acid 3-[(4-chloro-phenyl)-amide] 4-[(3-fluoro-4-[ 1,2,4]triazol-1 -yl-phenyl)-hydroxy-amide] 5 (3R>4R)-l-Methanesulfonyi-pyrrolidine-3?4-dicarboxylic add 3-[(4-chloro phenyl)-amide] 4-{[3-fluoro-4-(2-metiiyl-iiiiidazol-l-yl)-phenyl]-amide}> (3R,4R)-Pyrrolidine-3J4-dicarboxylic acid3-[(4-chloro-phenyi)-amide] 4-[(3-fluoro-2'-methylsulfanyl-biphenyl-4-yl)-amide], (3R>4R)-l-Methanesulfonyl-p)T:roHdine-3)4-dicarboxylic add 3-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} 4-[(4-methoxy-phenyl)-methyl-amide], (3R>4R)-l*Meiiaiiesulfoii)d-pyrrolidine-3)4-dicarboxylic add 3-(4-chloro-benzyiamide) 4-{[2-fluoro-4-(2-oxo-2H-p)oidiii-l-yi)-phenyl]-amide}, (3R,4R)-l-Metianesulfonyl-pyrrolidine-3,4-dicarboxyiic add 3-{[2-fluoro-4-(2-oxo-2H-p)Tidin-l-yl)-phenyl]-amide} 4-[(4-trifluoromethoxy-phenyl)-amide], (3R,4R)-l-(Propane-2-sulfonyl)-pyrroHdine-3,4-dicarboxylicadd3-[(4-diloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R,4R)-l-(2,2>2-Trifluoro-eiiianesulfonyl)-pyrroKdine-3,4--dicarbox)4icadd3-[(4-chloro-phenyl)-amidej 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yI)-phenyl]-amide}, (3R,4R)-l-Dimettylsulfamoyl-pyrrolidiae-3)4-dicarboxjdic acid 3-[(4-chloro-phen}d)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-3-(4-CHoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidine-l-carboxylic acid ethyl ester, (3R,4R)-3-(4-CKloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yI)-phenylcarbamoyl]-pyrrolidine-l-carbox}dic acid propyl ester, (3R,4R)-l-(Pyrrolidine-l-carbonyl)-pyrrolidine-3)4-dicarboxylic acid 3-[(4-chloro-phen"yi)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin- l-yl)-phenyl] -amide}, (3R,4R)- l-Metlianesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2)6-difluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}3 (3R,4R)-l-Meiiiaiiesulfoiiyl-p)7rrolidine-3>4-dicarboxylic add 3-[(4-chloro-phenyi)-amide] 4-{[2-fluoro-4-(6-oxo-6H-pyridazin-l-yl)-phenyl]-amide}> (3R,4R)-l-Methanesulfonyi-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro- phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-piperidin-l-7l)-phenyl]-amide}) (3R,4R)-l-Propanesulfonyl-pyrrolidine-3,4-dicarboxyiic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyI]-amide}, and (3R54R)-l-(2-Huoro-etiiyl)-pyrroHdine-3>4-dicarboxylic acid 3-[(4-chloro-phenyi)-amide] 4-{ [2-£luoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R54R)-Pyrrolidine-3J4"dicaxboX57iic add 3-[(4-chloro-phenyl)-ainide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yI)-phenyi]-amide}3 (3RJ4R)-3-(4-CHoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidine-l-carbosy]ic acid tert-butyl ester, (3R,4R)-Pyrrolidine-3,4-dicarboxyiic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4- (2-oxo-2H-pyridin-1 -yl)-phenyl] -amide}, (3 S,4S)-1-MetkanesiiLfonyl-pyrro^ amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R?4R)-l-Methanesulfonyi-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [4-(2?5-dihydro-p"5T:role-l-carbonyl)-phenyl]-amide}, (3R,4R)-l-Me1±Lanesulfonyi-pyrrolidine-334-dicarbo3qiic acid 3-[(4-chloro-phen"jd)-amide] 4-{[3-(morpholine«4-sulfonyl)-phenyl]-ainide}, (3R>4R)-l-Methanesulfonyi-pyrroHdine-3>4-dicarbox7^^ acid 3-[(4-chloro-phenyl)-ainide] 4-{[3-(4-methyl-pipera2ine-l-sulfonyi)-phenyl]-amide}, (3R,4R)-l-Metiianesulfonyl-pyrroUdine-3>4-dicarboxyiic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(morph.oline-4-carbonyl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-pyrrolidine-334-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(4-metiiyl-piperazine-l-carbonyl)-phenyl]-amide}; (3R,4R)-l-Methanesulfonyl-p)Trolidine-3?4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [4-(tliiomorpholine-4-carbonyl)-phenyl]-amide}, (3R,4R)-l-Methanesulfonyl-pyrroHdine-3?4-dicarbox5dicacid3-[(4-chloro-phenyi)-amide] 4-{ [4-(4-ethyi-piperazine-l-carbonyl)-phenyl] -amide}, (3R,4R)-l-Me1iianesulfonyl-pyrrolidiiie-3>4-dicarboxyiic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(4,4-difluoro-piperidine-l-carbonyl)-phenyl]-amide}, (3R,4R)-l-Meiiianesulfonyl-pyrrolidine-3)4-dicarbox)^lic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(4-fluoro-piperidine-l-carbonyl)-phenyl]-amide}, (3R,4R)-l-Metiianesulfonyl-pyrroHdine-3>4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(l-ox7-pyridin-2-yl)-phenyl]-amide}, (3R,4R)-l-(2)2-Difluoroethyl)-pyrrolidine-3,4-dicarbox7lic acid 3- [(5-chloro-pyridiB-2-yl)-amide] 4*{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Isopropyl-pyrroUdine-3)4-dicarbox7Kcacid3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} and pharmaceutically acceptable salts thereof. Particularly preferred compounds of formula (I) are those selected from the group consisting of (3R)4R)-l-(2>2-Difluoro-ethyl)-p)rrrolidine-3>4-dicarbox7Kc acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R»4R)-l-Eihaxiesulfonyl-pyrrolidine-334-dicarboxylic acid 3-[(4-chloro-phenyI)-amide] 4-{[2»fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-ainide}J (3R54R)-l-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R) -1 -Isopropyl-pyrrolidine-3?4-dicarboxylic acid 3- [ (4-chloro-phenyl) -amide] 4'{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyI]-amide}> (3R)4R)-l-Methanesulfonyl-pyrrolidine-3>4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2"fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}5 (3R,4R) -1 -Formyl-pyrroIidine-S^-dicarboxylic acid 3- [ (4-chloro-phenyl) -amide] 4-{ [2-fluoro-4-(2'Oxo-2H-pyridin-1 -yl)~phenyl] -amide}, (3R,4R)-l-(Propane-2-sulfonyl)-p}nTolidine-3>4-dicarboxylicacid3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)TidiQ-l-yl)-phenyl]-amide}, (3R,4R)-l-(272)2-Trifiuoro-ethanestdfonyl)-pyrroHdine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R?4R)-l-Dime1i)4sulfamoyl-pyrrolidine-3)4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl] -amide}, (3R,4R)-3-(4-Chloro-phenylcarbamoyl)-4-[2-fluoro-4'(2-oxo-2H-pyridin-l-yl)-phenylcarbamoylj-p'jTTolidine-l-carboxylic acid ethyl ester, and (3R,4R)-l-Propanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R)4R)-l-(2>2-Difluoroethyl)-pyrrolidine-3,4-dicarbox5rlic acid 3-[(5-chloro-p")T:idin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}, (3R,4R)-l-Isopropyl-pyrroHdine-3,4-dicarbox5rUcacid3-[(5-cUoro-pyridin-2--yI)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} and pharmaceutically acceptable salts thereof. It will be appreciated that the compounds of general formula (I) in this invention may be derivatised at functional groups to provide derivatives which are capable of conversion back to the parent compound in vivo. The invention further relates to a process for the manufacture of compounds of formula (I) as defined above, which process comprises a) reacting a compound of formula (II) with a compound LG-R\ or b) reacting a compound of formula (III) with a compound NHRR or c) reacting a compound of formula (IV) with a compound of formula (V) wherein R1, R2, R3, R4, R5, R7, R8, R9, and X have the significances given above and LG is a leaving group. The reaction of a compound of formula (II) with a compound LG-R1 is conveniently carried out in a solvent such as e.g. dichloromethane, THF, acetonitrile, DMF, DMA, DMSO, NMP etc. with bases like DIEA, triethylamine, pyridine, N-methylmorpholine, Na2CO3> K2CO3, CS2CO3 etc. Suitable leaving groups are well known in the art, e.g. halogenides, triflates, para-nitrophenolates or -mesylates. Suitable reaction conditions for the reaction of a compound of formula (IE) with, a compound NHR R or of a compound of formula (IV) "with a compound of formula (V) are well known to the person skilled in the art Such reactions can be carried out in a solvent such as e.g. dichloromethane, DMF, acetonitrile, THF> NMP, DMA, etc. and in the presence of an activating amide coupling reagent like EDC, DIC, DCQ GDI, TBTU, HBTUrEEDQ, CIP, HOBt, HATU, PyBOP, PyBrOP, BOP, BOP-C1, TFFH, isobutylcarbamoyl chloride, etc. at a suitable temperature, which can e.g. be chosen in the range of -10°C - 120°C. Moreover, the invention further relates to another process for the manufacture of compounds of formula (I) as defined above, which process comprises d) Reacting a compound of formula (VI) or (VTII) with a compound of formula (Vll)or (V), respectively: wherein R1, R2, R3> R4, R5, R7, R8, R9, and X have the significances given above, LG is a leaving group and R is lower alkyl, cycloalkyl or cycloalkyl-lower alkyL Suitable reaction conditions for the reaction of a compound of formula (VI) with, a compound NHR R are well known to the person skilled in the art. Such reactions can be carried out in a solvent such as e.g. DMF, acetonitrile, THF, toluene, heptane, and in the'presence of a strong base like trialkyl alumina, NaH, LiHMDS, KHMDS at a suitable temperature, which can e.g. be chosen in the range of-10°C-120°C. In all general reaction descriptions the saponification process can be also avoided. Reactions from the ester to the corresponding amides are also possible in each reaction sequence 2c) throughout 2f). General synthetic processes. 1. Synthesis of pym>Bdine-3,4-dicarboxylic acid scaffolds: General Procedure: An N-protected glycine derivative such as e.g. N-benzyl glycine is condensed with a source for formaldehyde like paraformaldehyde in a suitable solvent like benzene, toluene, xylene, DMF> DMA, DMSO or acetonitrile at elevated temperatures between 60-150 °C to the corresponding azomethine ylide. This species undergoes cycloaddition reactions with a suitable ester of fumaric acid like the corresponding diethyl ester or dimethyl ester in a one-pot procedure to yield the corresponding N-protected trans racemic mixture of pyrrolidine-3,4-dicarboxylic acid diesters. The N-protecting group is changed to the corresponding Boc- or Z-protecting group via cleavage of the first N-pxotecting group via e.g. catalytical hydrogenation. For this the protected pyrrolidine is dissolved in a suitable solvent like methanol, ethanol, THF or ethyl acetate followed by addition of a catalyst like Pd/C (e.g. 10%) to the mixture. After that a hydrogen atmosphere is generated to cleave the first N-protecting group. The free amine is then again protected by addition of B0C2O or Z-Cl, respectively. The last step is the complete saponification of the diester to the corresponding diadd. The pyrrolidine diester is dissolved in suitable solvent system like methanol, ethanols THF, l,4-dioxane> water or mixtures thereof and a base like LiOH, NaOH, KOH, Na2CO3, K2CO3 or CS2CO3 is added. Monohydrolysis can be performed using enantioselective enzymes or chiral bases in suitable solvents already described ox in buffered aqueous systems. 2, Modifactions of pyrrolidine scaffolds: a) Starting from N'Boc-pyrrolidine-3>4-dicarboxylic acids, introduction of R2-NH-R3 General Procedure: N-protected pyrrolidine-3,4-dicarboxylic acid is dissolved in a suitable solvent like dichloromethane, DMF, acetonitrile, THF, NMP, DMA, etc, and activated with an amide coupling reagent like EDC, DIC, DCC, CDI, TBTU, HBTU, EEDQ, CIP, HOBt, HATU, PyBOP, PyBrOP, BOP, BOP-C1, TFFH, etc. at -10°C - 120°C. By adding one to two equivalents of the amine R -NH-R the corresponding monoamide is obtained after reaction for 0.5-120 h at -10°C to 120 °C. Repetition of this reaction by using the same coupling reagents as mentioned above or transformation of the acid into the corresponding acid chloride or anhydride by means of oxalyl chloride, thionylchloride, isobutylcarbamoyl chloride or related reagents, with R4-NH-Y yields the corresponding diamide. After deprotection under standard conditions like treatment with acids (e.g. HC1, trifluoracetic acid, HBr in glacial acetic acid) or hydrogenation in the case of the Z-protecting group the unprotected pyrrolidine-l,3-dicarboxamide is reacted "with suitable reagents to introduce R1. Suitable reagents LG-R include alkylhalogenides (chlorides, bromides, iodides), -trifLates, -para-nitrophenolates, -mesylates, acidchlorides, sulfonic acid chlorides, carbamoylchlorides, sulfamides, sulfamidoylchlorides, aldehydes, ketones etc. and can be reacted in solvents like dichloromethane, THF, acetonitrile, DMF, DMA, DMSO> NMP etc. with bases like DIEA, triethylamine, pyridine, N-methylmorpholine, Na2CO3) K2CO3, Cs2CO3 etc. b) Starting from N-Boc-pyrrolidine-S^dicarboxyiic acids, introduction of R4-NH- Y General Procedure: Like 2a) "with a different order of the reaction sequence. c) Starting from £,i?~N-Boc-pyrroMine-3,4-dicarboxylic acid-3-ethylester> introduction of R2-NH-R3 General Procedure: Like 2a) with a different order of the reaction sequence and saponifi cation at step 2 as described for procedure 1. d) Starting from iJ,-R-N-Boc-pyrrolidine-3,4-dicarboxylic acid-3-ethylester, introduction of R4-NH-Y General Procedure: Like 2c) with a different order of the reaction sequence. e) Starling from iU^-N-Boc-pyrrolidine-34-dicarbo:xylic acid-3-ethylester, introduction of R2-NH-R3 and R1 J Chiral I chiral 00 0^0 H Chira! i, u M Deprotection \ / /\ fl " r^N R3 \ / Q + WSB R3 W N-Y >0 HD^>=0 K >*O R2' ^0 cT o o^ ra o o J) ?1 CWrai 'j11 Chiral N N LG_R1 ^ N 1. Saponification f N —- R^ )—( R3, M. N —/ 'ci= O 2. Amide formation ■ N —/ '^ o R2' o O R4 R2' Xo M ) N-Y R4' V General Procedure: Like 2c) -with a different order of the reaction sequence. f) Starting from^i^-N-Boc-pyrrolidiiie-S^-dicarboxylic atid-3-ethylester, introduction of R4-NH-Y and R1 General Procedure: Like 2c) with a different order of the reaction sequence. Analogous reactions can be performed with the corresponding S,S enatioiners. Insofar as their preparation is not described in the examples, the compounds of formula (I) as well as all intermediate products can be prepared according to analogous methods or according to the methods set forth above. Starting materials are commercially available or known in the art Furthermore, the invention relates to compounds of formula (I) as defined above, when manufactured by a process as described above. In another embodiment, the invention relates to the intermediates, the compounds of formula (H), (III) or (IV) wherein R1, R2, R3, R4, R5, R7, R8, R9 and X have the significances given above. As described above, the compounds of formula (I) are active compounds and inhibit the coagulation factor Xa. These compounds consequently influence both platelet activation which is induced by this factors and plasmatic blood coagulation. They therefore inhibit the formation of thrombi and can be used for the treatment and/or prevention of thrombotic disorders, such as, amongst others, arterial and venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease (PAOD)> unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke (cerebral thrombosis) due to atrial fibrillation, inflammation and arteriosclerosis. The compounds of the present invention can also be used in the treatment of acute vessel closure associated with thrombolytic therapy and restenosis, e.g. after transluminal coronary angioplasty (PTCA) or bypass grafting of the coronary or peripheral arteries and in the maintenance of vascular access patency in long term hemodialysis patients. F.Xa inhibitors of this invention may form part of a combination therapy "with an anticoagulant with a different mode of action or with a platelet aggregation inhibitor or with a thrombolytic agent. Furthermore, these compounds have an effect on tumour cells and prevent metastases. They can therefore also be used as antitumoux agents. Prevention and/or treatment of thrombotic disorders, particularly arterial or deep vein thrombosis, is the preferred indication. The invention therefore also relates to pharmaceutical compositions comprising a compound as defined above and a pharmaceutically acceptable carrier and/or adjuvant The invention likewise embraces compounds as described above for use as therapeutically active substances, especially as therapeutically active substances for the treatment and/or prophylaxis of diseases which are associated with the coagulation factor Xa, particularly as therapeutically active substances for the treatment and/or prophylaxis of thrombotic disorders, arterial thrombosis, venous thrombosis, deep vein thrombosis, peripheral arterial ocdusive disease, unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke due to atrial fibrillation, inflammation, arteriosclerosis, acute vessel closure associated with thrombolytic therapy or restenosis, and/or tumour In another preferred embodiment, the invention relates to a method for the therapeutic and/or prophylactic treatment of diseases which are associated with the coagulation factor Xa, particularly for the therapeutic and/or prophylactic treatment of thrombotic disorders, arterial thrombosis, venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease, unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke due to atrial fibrillation, inflammation, arteriosclerosis, acute vessel closure associated Math thrombolytic therapy or restenosis, and/or tumour, which method comprises administering a compound as defined above to a human being or animal. The invention also embraces the use of compounds as defined above for the therapeutic and/or prophylactic treatment of diseases which are associated with the coagulation factor Xa, particularly for the therapeutic and/or prophylactic treatment of thrombotic disorders, arterial thrombosis, venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease, unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism, stroke due to atrial fibrillation, inflammation, arteriosclerosis, acute vessel closure associated with thrombolytic therapy or restenosis, and/or tumour. The invention also relates to the use of compounds as described above for the preparation of medicaments for the therapeutic and/or prophylactic treatment of diseases which are asscociated with the coagulation factor Xa, particularly for the therapeutic and/or prophylactic treatment of thrombotic disorders, arterial thrombosis, venous thrombosis, deep vein thrombosis, peripheral arterial occlusive disease, unstable angina pectoris, myocardial infarction, coronary artery disease, pulmonary embolism* stroke due to atrial fibrillation, inflammation, arteriosclerosis, acute vessel closure associated with thrombolytic therapy or iestenosiSy and/or tumour. Such medicaments comprise a compound as described above. The inhibition of the coagulation factor Xaby the compounds of the present invention can be demonstrated with the aid of a chromogenic peptide substrate assay as described hereinafter. Factor Xa activity was measured spectrophotometrically in microtiter plates in a final volume of 150 pi using the following conditions: Inhibition of human factor Xa (Enzyme Research Laboratories) was tested at an enzyme concentration of 3 nM using the chromogenic substrate S-2222 (Chromogenix AB, Molndal, Sweden) at 200 nM. The reaction kinetics of lite enzyme and the substrate were linear with both time and the enzyme concentration. The inhibitors were dissolved in DMSO and tested at various concentrations up to 100 pM. The inhibitors were diluted using HNPT buffer consisting of HEPES lOOmM, NaCl 140mM, PEG 6000 0.1%-and Tween 80 0.02%, pH 7.8. The cleavage of S-2222 by human factor Xa was followed at 405 nm for 5 minutes at room temperature. The velocity of the reaction was determined by the autoreader from the slope of the linear regression fit to 7 time points (1 minute). The initial velocity for each inhibitor concentration was determined by the slope of at least 4 time points in the linear phase by a linear regression fit (mOD/min ). Apparent dissociation constants K* were calculated according to Cheng and Prusoff [Cheng, Y. G; Prusoff, W. H. Relationship between the inhibition constant (KO and the concentration of the inhibitor that causes 50 percent inhibition (IC50) of an enzyme reaction. Biochem. Pharmacol 1973,22, 3099-3108.] based on the IC50 and the respective Km, determined previously (K* = IC50/ (1+S/Km)). The Km for the substrate used was determined under the conditions of the test with at least 5 substrate concentrations ranging from 0.5 to 15 times Km. [Lottenberg R, Hall JA, Blinder M> Binder EP, Jackson CM., The action of thrombin on peptide p-nitroanilide substrates. Substrate selectivity and examination of hydrolysis under different reaction conditions. Biochim Biophys Ada. 1983 Feb 15; 742(3):539-57]. according to Eadie [Eadie G.S. The inhibition of cholinesterase by physostigmine and prostigmine. J. Biol. Chem, 1942,146, 85-93.]. The Km for S-2222 amounted to 613 fiM. The activity of the low molecular weight substances can, moreover be characterized in the "prothrombin time" (PT) clotting test. The substances are prepared as a 10 mM solution in DMSO and thereafter made up to the desired dilution in the same solvent Thereafter, 0.25 ml of human plasma (obtained from whole blood anticoagulated with 1/10 volume of 108 mM Na citrate) was placed in the instrument-specific sample container. In each case 5 yd of each dilution of the substance-dilution series was then mixed with the plasma provided. This plasma/inhibitor mixture was incubated at 37°C for 2 minutes. Thereafter, there were pipetted to the semi-automatic device (ACL, Automated Coagulation Laboratory (Instrument Laboratory)) 50 pi of plasma/ inhibitor mixture in the measurement container. The clotting reaction was initiated by the addition of 0.1 ml of Dade® Innovin® (recombinant human tissue factor combined with calcium buffer and synthetic phospholipids, Dade Behring, Inc., Cat. B4212-50). The time up to the fibrin cross-linking was determined photooptically from the ACL. The inhibitor concentration, which brought about a doubling of the PT clotting time, was determined by fitting the data to an exponential regression (XLfit). The compounds of the present invention can furthermore be characterised by the Activated Partial Thromboplastin time (aPTT). This coagulation test can e.g. be run on the ACL 300 Coagulation System (Instrumentation Laboratory) automatic analyzer. The substances are prepared as a 10 mM solution in DMSO and thereafter made up to the desired dilution in the same solvent. The test is performed with the Dade® Actin® FS Activated PTT reagent (purified soy phosphatides in l.OxlO^M ellagic acid, stabilizers and preservative, Dade Behring, Inc., Cat. B4218-100) Thereafter, 0.25 ml aliquots of human plasma (obtained from whole blood anticoagulated with 1/10 volume of 108 mM Na citrate) are spiked with 5 pi of test compound in at least 6 concentrations. 50 pi plasma at 4°C containing 1/50 vol. inhibitor in solvent are incubated with 50 pi Dade® Actin® FS Activated PTT reagent in water at 37°C for 3 min., then 50 pi CaCl2.2H2O 25 mM in water at 37°C are added. The time up to the fibrin cross-linking was determined photooptically from the ACL. The inhibitor concentration, which brought about a doubling of the APTT clotting time, was determined by fitting the data to an exponential regression (XLfit). The Ki values of the active compounds of the present invention preferably amount to about 0.001 to 50 pM, especially about 0.001 to 1 jiM. The PT values preferably amount to about 1 to 100 pM, especially to about 1 to 10 pM. The aPTT values preferably amount to about 1 to 100 pM, especially to about 1 to 10 pM. The compounds of formula I and/or their pharmaceuticaUy acceptable salts can be used as medicaments, e.g. in the form of pharmaceutical preparations for enteral, parenteral or topical administration. They can be administered, for example, perorally* e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions, rectally, e.g. in the form of suppositories, parenterally, e.g. in the form of injection solutions or suspensions or infusion solutions, or topically, e.g. in the form of ointments, creams or oils. Oral administration is preferred. The production of the pharmaceutical preparations can be effected in a manner which will be familiar to any person skilled in the art by bringing the described compounds of formula I and/or their pharmaceuticaUy acceptable salts, optionally in combination with other therapeutically valuable substances, into a galenical administration form together with suitable, non-toxic, inert, therapeutically compatible solid or liquid carrier materials and, if desired, usual pharmaceutical adjuvants. Suitable carrier materials are not only inorganic carrier materials, but also organic carrier materials. Thus, for example, lactose, corn starch or derivatives thereof, talc, stearic acid or its salts can be used as carrier materials for tablets, coated tablets, dragees and hard gelatine capsules. Suitable carrier materials for soft gelatine capsules are, for example, vegetable oils, waxes, fats and semi-solid and liquid polyols (depending on the nature of the active ingredient no carriers might, however, be required in the case of soft gelatine capsules). Suitable carrier materials for the production of solutions and syrups are, for example, water, polyols, sucrose, invert sugar and the like. Suitable carrier materials for injection solutions are, for example, water, alcohols, polyols, glycerol and vegetable oils. Suitable carrier materials for suppositories are, for example, natural or hardened oils, waxes, fats and semi-liquid or liquid polyols. Suitable carrier materials for topical preparations are glycerides, semi-synthetic and synthetic glycerides, hydrogenated oils, liquid waxes, liquid paraffins, liquid fatty alcohols, sterols, polyethylene glycols and cellulose derivatives. Usual stabilizers, preservatives, wetting and emulsifying agents, consistency-improving agents, flavour-improving agents, salts for varying the osmotic pressure, buffer substances, solubilizers, colorants and masking agents and antioxidants come into consideration as pharmaceutical adjuvants. The dosage of the compounds of formula I can vary within wide limits depending on the disease to be controlled, the age and the individual condition of the patient and the mode of administration, and will, of course, be fitted to the individual requirements in each particular case. For adult patients a daily dosage of about 1 to 1000 mg, especially about 1 to 300 mg, comes into consideration. Depending on severity of the disease and the precise pharmacokinetic profile the compound could be administered with one or several daily dosage units, e.g. in 1 to 3 dosage units. The pharmaceutical preparations conveniently contain about 1-500 mg, preferably 1-100 mg, of a compound of formula I. The following Examples serve to illustrate the present invention in more detail. They are, however, not intended to limit its scope in any manner. Examples Example 1 trans-(3RS,4RS)-l-Methanesulfo^ acid 3-[(4- chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p^Ti.din-l-yl)-phenyl]-ainide} According to the general method 2a) Stepl: trai2S'(3RSy4RS)'l'Benzyl-p)n'olidme-3}4-dicarhox}dic add diethyl ester la Fumaric acid diethylester (21.6 g; 0.126 mol) is dissolved in toluene (900 ml) and heated at 105 °C. A mixture of N-benzylglycine (25 g; 0.151 mol) and paraformaldehyde (25.36 g; 0.844 mol) is added in 4 g portions to the refluxing solution. After completion of the addition the mixture is heated for 18 h at 105°C. The mixture is then evaporated to dryness and suspended in n-hexane. The insoluble material is filtered off and the remaining solution is evaporated to dryness. The crude product is used for the next step without further purification. Yield: 32.5 g (70.3 %), ESI-MS: m/z = 306 [M+H]+ Step 2: traiis-(3RS,4RS)-Pyrrolidine-l,3,4-tricarbox)dic acid tert-butyl ester diethyl ester lb Under argon-atmosphere compound la (32.5 g; 0.106 mol) and di-£er£-butyldicarbonat (24.4 g; 0.112 mol) are dissolved in ethanol (650 ml). After that palladium on charcoal (10%; 3.4 g; 0.0034 mol) is added under argon-atmosphere and the argon-atmosphere is changed to hydrogen-atmosphere. After 2 h at 25°C the hydrogenation is completed and palladium on charcoal is filtered off. The filtrate is evaporated to dryness and the residue is purified with flash chromatography over silica gel (700 g) using n-heptane/ethyl acetate (2:1) as eluent. Yield: 25.4 g (75.7 %), ESI-MS: m/z = 316 [M+H]+ Step 3: trans-(3RS>4RSyPyrrolidine'l)3i4-tricarboxylic acid tert-butyl ester 1c Compound lb (1 g> 3.17 mmol) was dissolved in of THF (8 ml), and 80 mL of water was added. The reaction mixture was immersed in an ice-water bath and cooled to 0 C. To this reaction mixture, 96 ml of 0.25 N NaOH was added in small portions with stirring until the consumption of the starting diester was detected by thin-layer chromatography. The reaction was stirred at the same temperature for about 30 min to 1 h> and the reaction mixture was acidified with 1 N HC1 at 0 °Q saturated with NaCl, extracted with ethyl acetate four times (each 100 ml), and dried with sodium sulfate. The organic phase is evaporated to dryness and dried in vacuo. Yield: 0.68 g (82.7%), ESI-MS: m/z = 258 [M-H]" Step 4: trzii.&-(3RS>4RS)-4-(4-Chlorophenylcarbamoyl)-fy add 1-tert-butyl ester Id Compound lc (2.25 g; 9 mmol) is suspended in acetonitriie (30 ml) and N,N-diisopropyl ethyl amin (3.03 ml; 17 mmol) is added at 25 °C. After 20 min a dear solution is obtained and 1 -(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDCI (2.0 g; 10 mmol) and 1-hydroxybenzotriazole HOBt (1.41 g; 10 mmol) is added After stirring for 30 min at 25°C 4-chloroaniline (1.11 g; 9 mmol) is added to the reaction mixture. The mixture is stirred for 18 h at 25°C, evaporated to dryness and dissolved in ethyl acetate (100 ml). The organic phase is washed with 0.1 N HC1 (2 x 100 ml), water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. Yield: 1.08 g (33.7%), ESI-MS: m/z = 368 [M-H]", C]-pattern Step 5: l~(4-Amino-3-fluoro--phenyl)-lH-pyridin'2-o?te le 4-Bromo-2-fluoroaniline (13.0 g; 68 mmol), 2-hydroxypyridine (9.11 g; 96 mmol), 8-hydroxyquinoline (1.5 g; 10 mmol) are dissolved under argon in DMSO (40 ml). To this solution K2CO3 (10.4 g; 75 mmo!) and Cul (1.95 g; 10 mmol) are added and the resulting suspension is heavily stirred under argon at 150°C for 18 h. The mixture is evaporated to dryness under reduced pressure and the final residue is chromatographed over silica gel (400 g) using dichloromethane/methanol as eluents. The obtained crude product is recrystallized with diethyl ether to yield an off-white solid. Yield:'2.80 g (20.0 %), ESI-MS: m/z = 205 [M+H]+ Step 6: tran$-(3RS,4RS)-Pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)' amide] 4-{{2-fluoro~4-(2~oxo-2H-pyridin-l-yl)-phertyl]-amide} hydrochloride If Compound Id (0,8 g; 2 mmol) is dissolved in thionylchloride (3.93 ml; 54 mmol), after 30 min stirring at 25 °C l-(4-amino-3-fluoro-phenyl)-lH-pyridin-2-one (compound le, 0.443 g; 2 mmol) is added under cooling. The mixture is stirred for 18 h at 25 °C, evaporated to dryness and recrystallized from diethyl ether yielding compound I/as light brown solid as hydrochloride. Yield: 0.872 g (81.8 %), ESI-MS: m/z = 455 [M+Hr> Cl-pattern Step 7: traiis-(3RSy4RS)'l'Me^ia7iesulfonyl-pynolidine'334-dicarboxylic acid 3-[(4-chloro~phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)~phenyl]-amide} Ig Compound If (803 mg; 0.177 mmol) is dissolved in acetonitrile (3 ml) under addition of N>N-diisopropyl ethyl amine (45.75 mg; 61.8 \xl; 0.354 mmol). Methanesulfonylchloride (40.6 mg; 0.354 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 11.2 mg (11.9 %), ESI-MS: m/z = 533 [M+H]+, Cl-pattern Example 2 trans-(3RS>4RS)-l-Fonnyl»p)TTondine»354-dicarboxyHcacid3-[(4-cUoro-phenyl)-amide] 4-{[2-fluoro-4~(2-oxo-2H-pyridin-l-yl)-phenyI]-amide} The compound of example 2 was prepared as described for example 1 with the exception of step 7 Step 7: tra7i$-(3RS,4RS)-l-Fonn)d~p)rrolidine-3,4-dicarboxylic add 3-[(4-chloro-phenyl)-amidt] 4-{{2-fluoro-4-(2-oxO'2H-pyridin-l-yl)-phenyl]-amide} 2 . Compound If (80.3 mg; 0.177 mmol) is dissolved in acetonitrile (3 ml) under addition of N,N-diisopropyl ethyl amine (22.9 mg; 30.9 yl; 0.177 mmol). 4-Nitrophenylfonniate (29.6 mg; 0.177 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 13.8 mg (16.1 %), ESI-MS: m/z = 483 [M+H]+> Cl-pattern Example 3 trans-(3RS>4RS)-{3-(4-Chloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidin-l-yl}-acetic acid ethyl ester The compound of example 3 was prepared as described for example 1 with the exception of step 7 Step 7: trans-(3RS,4RS)-{3-(4-Chbro-phenylcarbamoyl)-4'[2-flu^ pyridiit-~l-yl)-phenylcarbamoyl]--pyrrolidin-l-yl}-acetic add ethyl ester 3 Compound If (80,3 mg; 0.177 mmol) and K2CO3 (69.0 mg; 0.5 mmol) are suspended in acetonitrile (3 ml). After that bromo acetic acid ethyl ester (32.5 mg; 0.195 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC . chromatography. Yield* 18.8 mg (19.6 %), ESI-MS: m/z = 541 [M+Hf5 Cl-pattern Example 4 trans-(3RS,4RS)- l-Carbamoylmethyl-p^TroHdine-S^dicarboxyiic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxO"2H-pyridin-l"yl)-phen7l]»amide} The compound of example 4 was prepared as described for example 1 -with the exception of step 7 Step 7: Uans-(3RS>4RS)A-Carbamoylmethyl-pynolid^ add 3-[(4- chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-pheiiyl]-amide} 4 Compound If (80.3 mg; 0.177 mmol) and K2CO3 (69.0 ing; 0.5 mmol) are suspended in acetonitrile (3 ml). After that 2-bromo-acetamide (27.0 mg; 0.195 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 10.8 mg (11.9 %), ESI-MS: m/z = 512 [M+H]+> Cl-pattern Example 5 trans-(3RS,4RS)-l-Cyanomethyl-pyrrolidine-3,4-dicarboxylic acid 3- [(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4-(2-oxo-2H-pyridin-1 -yl)-phenyl]-amide} The compound of example 5 was prepared as described for example 1 with the exception of step 7 Step 7: trans- (3RS,4RS)-1-Cyanomethyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4~(2-oxO'2H-pyridi7t-l~yl)-phenyl]-amide} 5 Compound If (80.3 mg; 0.177 mmol) and K2CO3 (69.0 mg; 0.5 mmol) are suspended in acetonitrile (3 ml). After that 2-bromo-acetonitrile (23.4 mg; 0.195 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 10.4 mg (11.9 %), ESI-MS: m/z = 494 [M+H]+, Cl-pattern Example 6 lxans-(3RS,4RS)-l-(3,33-Trifluoro-propyl)-pyrroHdine-354-dicarbosylic acid 3- [(4-chloro-phenyl)-amide]-4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]- amide} The compound of example 6 was prepared as described for example 1 with the exception of step 7 Step 7: tram-(3RS,4RS)-l-(3,3,3-TrifiuoTO-propyl)-p)rro^ add 3-[(4-chhro-phenyl)-amide]-4-{[2-ffa 6 Compound If (80.3 ing; 0.177 mmol) and K2CO3 (69.0 mg; 0.5 mmol) are suspended in acetonitrile (3 ml). After that 3-bromo-l,l,l-txifluoropropane (34.5 mg; 0.195 mmol) and Ag2O (45.2 mg; 0.195 mmol) is added and the mixture is stirred for 18 h at 80 °C The reaction mixture is evaporated to dryness and purified with preparative HPLC chromatography. Yield: 19.7 mg (20.2 %), ESI-MS: m/z = 551 [M+H]+, Cl-pattern Example 7 (3R,4R)-l-Metiianesiilfon7l-pyrrolidine-3,4-dicarbox7lic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yi)-phenyl]-amide} According to general method 2c) Step 1: (3R,4R)-Pyrrolidine-ly3,4-tricarboxylic add-1-tert-butyl ester-3-ethyl ester 7a The stereoselective mono saponification of the racernic mixture of compound lb to compound 7a and the correpsonding S,S-enantiomer is described in: R.M. Rodriguez Sarmiento, B. Wirz, H. Iding, Tetrahedron Asymmetry, 14> 2003, 1547-1551. Step 2a: (3RAR)'4~(4-Chlorophe7zylcarbamoyl)'p)Trolidi?te'lf3-dicarboxylic acid 1-tert-butyl ester- 3-ethyl ester 7b Compound 7a (4.91 g; 17.1 mmol) is suspended in acetonitrile (25 ml) and N,N-diisopropyl ethyl amin (3.58 ml; 20.5 mmol) is added at 0 °C. Bis (2-oxo-3-oxazolidinyl) phosphinic chloride BOP-C1 (5.22 g; 20.5 mmol) is added as a solid and after stirring for 30 min at 0°C 4-chloroaniline (2.18 g; 17.1 mmol) is added to the reaction mixture. The mixture is stirred for 2 h at 0°C, evaporated to dryness and dissolved in ethyl acetate (ml). The organic phase is washed with 0.1 N HC1 (2 x ml), with saturated aquous Na2CC>3 solution, water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography. Yield: 4.7 g (69.3 %), ESI-MS: m/z = 395 [M-H]"> Cl-pattern Step 2b: (3RJ4R)-4'(4'Chlorophenylcarbamoyl)-pynolidine-l>3'dicarboxylic acid 1-tert-butyl ester 7c The ester obtained from step 2a (4.07 g; 10.3 mmol) is dissolved in a mixture of THF/water (1:1; 40 ml). LiOH monohydrate (0.947 g; 22.6 mmol) is added to the mixture and complete saponification is obtained after stirring for 18 h at 25°C. The mixture is acidified with. IN aq. HC1 and diluted with ethyl acetate (100 ml). The organic phase is washed with brine (100 ml) and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. Yield: 3.28 g (86.7 %)> ESI-MS: m/z = 367 [M-H]\ Cl-pattern Step 3: (3R,4R)-Pyrrolidine'3}4~dicarboxyUc acid 3-[(4-chloro-pheityl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} hydrochloride 7d Compound 7c (2.2 g; 5.96 mmol) is dissolved in thionylchloride (10 ml) and stirred at 25°C for 30 min. After that l-(4-amino-3-fluoro-phenyl)-lH-pyridin-2-one (compound le; 1.22 g; 5.96 mmol) is added and the reaction mixture is stirred for 18 h at ambient temperature. The mixture is evaporated to dryness and the crude product is recrystallized from diethylether several times to yield compound 7d as light brown solid Yield: 2.92 g (99.7 %), ESI-MS: m/z = 455 [M+H]+, Cl-pattern Step 4: (3RAR)'l-MethaiiesulfonyUp)nrolidme'3A'dicarboxylic add 3-[(4-chloro-pheityl)-a?nide] 4~{[2-fluoro-4-(2-oxo-2H-pyridinA~yiyphaiyl]-amide} 7e Compound 7d (300 mg; 0.61 mmol) is dissolved in acetonitrile (5 ml) under addition of N,N-diisopropyl ethyl amine (210 pi; ■ 1.22- mmol). -Methanesulfonylchloride (140 mg; 1.22 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 170 mg (5.22 %), ESI-MS: m/z = 533 [M+H]+, Cl-pattern Example 8 (SR^^-l-Ethanesulfonyl-pyrrolidine-Sj^dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-£luoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 8 was prepared according to the methods described for example 7. ESI-MS: m/z = 547 [M+H]+> Cl-pattern Example 9 (3R,4R)-l-Propanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyI]-amide} The compound of example 9 was prepared according to the methods described for example 7. ESI-MS: m/z = 561 [M+H]+, Cl-pattern Example 10 (3R)4R)-l-(Propane-2-sulfonyI)-pyrrolidine-3J4-dicarbox7lic acid 3-[(4-chloro-phenyi)-amide] 4-{[2-fluoro-4- (2-oxo-2H-pyridin-1 -yl)-phenyl] -amide} The compound of example 10 was prepared according to the methods described for example 7. ESI-MS: m/z = 561 [M+H]+, Cl-pattern Example 11 (3R>4R)-l«(2>2>2"Trifluoro-ethanesulfonyl)-pyrroUdine-3>4-dica^^ acid 3- [ (4-chloro-phenyl)-amide] 4-{ [2-fluoro-4- (2-oxo-2H-pyridin- l-yl)-phenyl] - amide} The compound of example 11 was prepared according to the methods described for example 7. ESI-MS: m/z = 601 [M+H]+, Cl-pattern Example 12 (SR^RJ-l-Dimethylsulfainoyl-pyrrolidine-S^dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4- {[2-fluoro-4- (2-oxo-2H-pyridin* 1 -yl)-phenyl] - amide} The compound of Example 12 was prepared according to the methods described for example 7. ESI-MS: m/z = 562 [M+H]+, Cl-pattern Example 13 (3R,4R)«l-Acetyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4»chIoro-phenyI)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of Example 13 was prepared according to the methods described for example 7. ESI-MS: m/z = 497 [M+H]+, Cl-pattern Example 14 (3R,4R>3- (4-Chloro-phenylcarbamoyl)-4- [2-fluoro-4- (2-oxo-2H-pyridin- l-yl)-phenylcaxbamoyl] -pyrrolidine-1 -carboxylic acid methyl ester The compound of example 14 was prepared according to the methods described for example 7. ESI-MS: m/z = 513 [M+H]+, Cl-pattern Example 15 (3R»4R)-1- (2-Fluoro-ethyl)-pyrrolidine-3 ,4-dicarboxylic acid 3- [ (4-dhloro-phenyl)-amide] 4-{[2~fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 15 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in acetonitrile (2 ml) under addition K2CO3 (56 mg; 0.4 mmol). 2-Fluoroethylbromide (59 mg; 0.41 mmol) and Ag2O (47 mg; 0.2 mmol) is added to the reaction mixture. The mixture is stirred at 80°C until a fall conversion to example 23 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 20 mg (18.9 %), ESI-MS: m/z = 501 [M+H]+, Cl-pattern Example 16 (3R,4R)-3-(4-CUoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamo)d]-pyrrolidine*l-carboxyKc acid ethyl ester The compound of example 16 was prepared according to the methods described for example 7. ESI-MS: m/z = 527 [M+H]+> ei-patterrr Example 17 (3R>4R)-3-(4-CWoro-phenyIcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-p^din-l-yl)-phenylcarbamoylj-pyrrolidine-l-carboxylic acidpropyl ester The compound of example 17 was prepared according to the methods described for example 7, ESI-MS: m/z = 541 [M+H]+> Cl-pattern Example 18 (3R,4R)-3-(4»Chloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidine-l-carboxylic acid isopropyl ester The compound of example 18 was prepared according to the methods described for example 7. ESI-MS: m/z = 541 [M+H]^, Cl-pattern Example 19 (3R»4R)- l-(Pyrrolidine- l-carbonyl)-pyrrolidine-3,4-dicarboxyiic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H"pyridin-l«yl)-phenyL]-amide} The compound of example 19 was prepared according to the methods described for example 7. ESI-MS: m/z = 552 [M+H]\ Cl-pattern Example 20 (3 S,4S)-1 -Methanesulfonyl-pyrrolidine-3>4-dicarboxylic acid 3- [(4-chloro-phenyl)-amide] 4-{ [2-fluoro-4- (2-oxo-2H-pyridin-1 -yl)~phenyl]-amide} The compound of example 20 was prepared according to the methods described for example 7 starting from the (3S, 4S)-enantiomer. ESI-MS: m/z = 533 [M+H]+> Cl-pattern Example 21 (3R,4R)-l-Sxdfamoyl-pyrrolidine-3>4-dicarboxylic acid 3-[(4n:hloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l"yl)"phenyl]-amide} The compound of example 21 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in diglyme (1 ml). The mixture is heated at 160 °C and a solution of sulfamide (23 mg; 0.24 mmol) in diglyme (1 ml) is dropped to the reaction mixture within 5 min. The reaction mixture is heated at 160 °C until a full conversion to example 21 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC Yield: 4 mg (3.7 %), ESI-MS: m/z = 534 [MH-H]+5 Cl-pattern Example 22 (3R)4R)-l*Formylpyrrolidine'3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4- {[ 2-fluoro-4- (2-oxo-2H-pyridin-1 -yl) -phenyl] -amide} The compound of example 22 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in acetonitrile (2 ml) under addition of N>N-diisopropyl ethyl amine (30 (il; 0.2 mmol). Formic acid-4-nitrophenyi ester (34 mg; 0.2 mmol) is added to the reaction mixture. The mixture is stirred at ambient temperature until a full conversion to example 22 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 40.4 mg (41.1 %), ESI-MS: m/z = 483 [M+H]+, Cl-pattern Example 23 (3R>4R)-l-(2,2>2-Trifluoro-ethyI)-pyrrolidine-3,4-dicafboxjdic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-ainide} The compound of example 23 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (80 mg; 0.16 mmol) is dissolved in dichloromethane (2 ml) under addition of NJSI-diisopropyl ethyl amine (60 \sl; 0.41 mmol). 2>2>2-Trifluoroethyltriflate (57 mg; 0.24 mmol) is added to the reaction mixture. The mixture is stirred at ambient temperature until a full conversion to example 23 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 10.0 mg (11.4 %), ESI-MS: m/z = 537 [M+H]+, Cl-pattern Example 24 (3R,4R)- l-(2>2-Difluoro-ethyl)-pyrrolidine-3>4-dicarboxylic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p^Tidin-l-yl)-phenyl]-amide} The compound of example 24 was prepared according to the methods described for example 7 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in acetonitrile (2 ml) under addition K2CO3 (56 mg; 0.4 mmol). 2,2-Difluoroethylbromide (59 mg; 0.41 mmol) and Ag^O (47 mg; 0.2 rnrnol) is added to the reaction mixture. The mixture is stirred at 80°C until a full conversion to example 23 is observed. The reaction mixture is evaporated to dryness and purified with preparative HPLC. Yield: 20 mg (18.9 %), ESI-MS: m/z = 519 [M+H]+, Cl-pattern Example 25 ■ (3R)4R)-l-(2-Hydroxy-etiiyl)-pyrroUdhie--3)4-dicarl)Oxylic acid 3- [(4-chloro-phenyl)-amide] 4-{[2-£luoro-4-(2-oxo-2H-pyridin-l-yi)-phenyi]»ainide} The compound of example 25 was prepared according to the methods described for example 24. ESI-MS: m/z = 500 [M+H]+, Cl-pattern Example 26 (3R,4R)-1-Methylcarbamoy]meft^ acid 3-[(4- chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 26 was prepared according to the methods described for example 24. ESI-MS: m/z = 526 [M+H]+, Cl-pattern Example 27 (3R,4R)-l-Isopropyl-pyrrolidine"3J4-dicafboxylic acid 3~[(4-chloro-phenyl)-ainide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 27 was prepared according to the methods described for example 24 with the exception of step 4. Step 4: Compound 7d (100 mg; 0.2 mmol) is dissolved in a mixture of methanol and acetic acid (9:1; 2 ml). Aceton (24 mg; 0.41 mmol) is added and the reaction mixture is stirred for 30 min at 25°C. After that NaBH3CN (45 mg; 0.71 mmol) is added to the mixture. After stirring for 18 h at ambient temperature the reaction mixture is treated once again with aceton (24 mg; 0.41 mmol) and NaBHsCN (45 mg; 0.71 mmol) and stirred at 80 °C for 18 h. After that the mixture is evaporated to dryness and purified with preparative HPLC. Yield: 3 mg (3 %), ESI-MS: m/z = 497 [M+H]+, Cl-pattern Example 28 (3R)4R)-l-Methanesulfonyl-pyrroIidine-3,4-dicarboxylic acid 3-{[2-fLuoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} 4-[(lH-indol-5-yl)-amide] According to general method 2d) Step 1: (3RAR)'Pyrrolidine-l,3A-tricarbox)rlic acid-1-tert-butyl ester-3-ethyl ester 7a The stereoselective mono saponification of the racemic mixture of compound 1b to compound 7a and the correpsonding S,S-enantiomer is described in: R.M. Rodriguez Sanniento, B. Wirz, H. Iding, Tetrahedron Asymmetry, 14, 2003, 1547-1551. Step 2: (3RM)-4'[2-Fluoro~4-(2'OXo-2H'pyndin'l-yl)-phenykarbamoyl]-py7Tolidine-l,3-dicarbox)dic add 1 -tert-butyl ester 3-ethyl ester 28b Compound 7a (1.85 g; 6 mmol) is suspended in acetonitrile (20 ml) and N,N-diisopropyl ethyl amin (1.65 ml; 10 mmol) is added at 25 °C. BOP-C1 (2.46 g; 10 mmol) is added as a solid and after stirring for 30 min at 25°C l-(4-amino-3-fluoro-phenyl)-lH-pyridin-2-one (1.45 g; 7 mmol) is added to the reaction mixture. The mixture is stirred for 4 d at 25°C, evaporated to dryness and dissolved in ethyl acetate (200 ml). The organic phase is washed 'with 2 N HC1 (50 ml), with 10% aqueous Na2CC>3 solution, water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography. Yield: 1.77 g (58.1 %), ESI-MS: m/z = 472 [M-H]- Step 3: (3R,4R)-4- [2-¥luoro-4- (2-oxo-2H-pyridin-1 -yl)-phmylcarbamoyl]-pyrrolidine-3-carbox)>lic add ethyl ester hydrochloride 28c Compound 28b (5.37 g; 11 mmol) is dissolved in 6 N HC1 in isopropanol (42 ml) and the mixture is stirred for 2 h at 25°C. The mixture is evaporated to dryness and the crude product is recrystallized from diethylether several times to yield compound 28c as an off-white solid. Yield: 4.89 g (105.2%), ESI-MS: m/z = 374 [M+H]+ Step 4: (3R,4R)-4-[2-Muoro-4-(2-oxo-2H-p)ridi77'l-yl)-phe7rylca^ methane-sulfonyl-pyrrolidiiie-3-carboxylic add ethyl ester 28d Compound 28c (3.1 g; 8 mmol) is suspended in acetonitrile (20 ml) under addition of N,N-diisopropyl ethyl amine (3.24 ml; 19 mmol). Methanesulfonylchloride (1.3 g; 11 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dqmess and purified by silica gel chromatography. Yield: 3.5 g (102.5 %), ESI-MS: m/z = 450 [M-H]~ Step 5: (3R,4R)-4-[2-Ruoro-4-(2-oxo-2H-pyridi77'l-yl)-phenylcarbamoyl]-l-methane~sulfonyl-pyrrolidine-3-carboxylic add 28e Compound 28d (3.7 g; 8 mmol) is dissolved in a mixture of 1,4-dioxane/water (1:1; 30 ml). LiOH monohydrate (1.03 g; 25 mmol) is added.to the mixture and complete saponification is obtained after stirring for 24 h at 25°C. The mixture is evaporated to dryness- and dissolved in ethyl acetate and the product is extracted with saturated aqueous Na2CO3 solution. The aqueous phase is cooled to 10 °C and acidified with 25% aqueous HC1 solution until pH = 1. The product is extracted several times with ethylacetate (3 x 100 ml). The combined organic phases are washed with brine and dried over Na2SC>4. After filtration the organic phase is evaporated to dryness. Yield: 1.57 g (45.2 %), ESI-MS: m/z = 422 [M-H]" Step 6: (SR^yi'MethaiiesulfonyJ'pyrrolidiyte'S^dicarboxylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridin-l~yl)~phmyl]-amide} 4-[(lH-indol-5-yl)-amide] 28f Compound 28e (100 mg; 0.236 mmol) is suspended in acetonitrile (1 ml) and N,N-diisopropyl ethyl amin (60 |ii; 0.354 mmol) is added at 25 °C. BOP-C1 (90 rng; 0. 354 mmol) is added as a solid and after stirring for 30 min at 25°C 5-amino indole (34 mg; 0.286 mmol) is added to the reaction mixture. The mixture is stirred for 18 h at 25°C, evaporated to dryness and purified by silica gel chromatography. Yield: 88 mg (69.3 %), ESI-MS: m/z = 538 [M+Hf Example 29 (3R^R)-l-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridin-1 -yl) -phenyl] -amide} 4- [ (4-methoxy-phenyl) -amide] The compound of example 29 was prepared according to the methods described for example 28. ESI-MS: m/z = 529 [M+H]+ Example 30 (3R,4R)- l-MethanesulfonyI-pyrrolidine-3,4"dicarboxylic acid 3- [(3-chloro-4-methoxy-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-p)7ridin-l-yl)-phenyl]-amide} The compound of example 30 was prepared according to the methods described for example 28. ESI-MS: m/z = 563 [M-f H]+, Cl-Pattern Example 31 (3R,4R)- l-Methanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3- [ (3-fluoro~4-methoxy-phenyl)-ainide] 4- {[2-fluoro-4-(2-oxo-2H-pyridin-1 -yl)-phenyl] -amide} The compound of example 31 was prepared according to the methods described for example 28. ESI-MS: m/z = 547 [M+H]+ Example 32 (3RJ4R)-l-MeAanesiilfon7l-pyrroKdine--3)4-dicarboxyiic acid 3-[(4-chloro-3-£luoro-phenyl)-ajnide]4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yi)-phenyl]-ainide} The compound of example 32 was prepared according to the methods described for example 28. ESI-MS: m/z = 551 [M+H]+, Cl-Pattern Example 33 (3R54R)-l-Methanesxilfon7l-pyrrolidine-3)4-dicarbox7lic acid 3-[(4-chloro-2-ftuoro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 33 was prepared according to the methods described for example 28. ESI-MS: m/z = 551 [M+H]+, Cl-Pattern Example 34 (3R,4R)-l-Methanesulfonyl-pyrrolidine-3>4-dicarboxylic acid 3-[(2-amino-4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 34 was prepared according to the methods described for example 28. ESI-MS: m/z = 548 [M+H]+> Cl-Pattern Example 35 (3R)4R)-l-Methanesulfonyl-pyrroIidine-3,4-dicarboxyUc acid 3-[(4-chloro-phenyl)-methyl-ainide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)«phenyl]»amide} The compound of example 35 was prepared according to the methods described for example 28. ESI-MS: m/z = 547 [M-hH]+, Cl-Pattern Example 36 (3R?4R)-l-Methanesxdfonyl-pyrrolidine-3,4-dicarboxylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide}4-[(lH-indazol-5-yl)-amide] The compoimd of example 36 was prepared according to the methods described for example 28. ESI-MS: m/z = 539 [M+H]+ (3R)4R)-l-MetiiajQesulfon7l-pyrroUdine-3)4-dic^xboxyiic acid 3-[(5-chloro-pyridin-2-yi)-amide] 4-{ [2-fluoro«4- (2-oxo-2H-pyridin-1 -yl)-phenyl] -amide} The compound of example 37 was prepared according to the methods described for example 28 with the exception of step 6. Step 6: Compound 28e (35 mg; 0.083 mmol) is dissolved under argon in thionylchlorid (0.03 ml; 0.413 mmol) to generate the corresponding acidchlorid. The mixture is stirred for 30 min at 25 °G 2-Amino-chloro pyridine is dissolved in THF and NaH suspension in oil (55%; 24 mg; 0.58 mmol) is added under hydrogen evolution. The mixture is stirred for 30 min at 25°C. The corresponding addchloride solution is added to the reaction mixture of the deprotonated 2-amino-chloro pyridine. The combined suspensions are stirred for 7 d at 25°C. The reaction suspension is evaporated to dryness and purified by silica gel chromatography. Yield: 36 mg (81.5 %), ESI-MS: m/z = 534 [M+H]+, Cl-Pattern Example 38 (3R,4R)*l-Methanesulfonyl-pyrrolidine-3>4-dicarbox5iic acid 3-(4-chloro-benzylamide) 4- {[2-fluoro-4~ (2-oxo-2H-pyridin~l -yl)-phenyl] -amide} The compound of example 38 was prepared according to the methods described for example 28. ESI-MS: m/z = 547 [M+H]+, Cl-Pattern Example 39 (3R,4R)-l-Methanesxilfonyl"pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro- phenyl)-amide] 4-{[2-fluoro-4-(3-methoxy-2-oxo-2H-pyridin-l-yl)-phenyl]- amide} According to general method 2e) Step 1; (3R,4R)-P)nTolidine-l,3t4-triearboxyIic add-1-tert-butyl ester-3-ethyl ester 7a The stereoselective mono saponification of the racemic mixture of compound ib to compound 7a and the correpsonding S,S-enantiomer is described in: R.M. Rodriguez Sarmiento, B. Wirz, H. Iding, Tetrahedron Asymmetry, 14, 2003, 1547-1551. Step 2a: (3R,4R)-4-(4-Chlorophenylcarba?noyl)'p)nrolidine-l,3-dicarboxylic acid 1-tert-butyl ester-3-ethyl ester 39 b Compound 7a (1 g; 3.48 mmol) is suspended in acetonitrile (7 ml) and N,N-diisopropyl ethyl amin (1.22 ml; 6.96 mmol) is added at 25 °C. BOP-Q (1.772 g; 6.96 mmol) is added as a solid and after stirring for 30 min at 25°C 4-chloroaniline (0.444 g; 3.48 mmol) is added to the reaction mixture. The mixture is stirred for 18 h at 25°C, evaporated to dryness and dissolved in ethyl acetate (100 ml). The organic phase is washed with with saturated aquous Na2CO3 solution (100 ml), 2 N HC1 (50 ml), water and brine and dried over Na2SC>4, The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography Yield: 0.5 g (36.2 %), ESI-MS: m/z = 395 [M-H]", Cl-pattern Step 3: (3R,4R)-4-(4^Chloro-phe?iylcarbamoyl)-pyrrolidine-3-carboxylic acid ethyl ester hydrochloride 39c Compound 39b (1.6 g; 4.03 mmol) is dissolved in 6N HQ in isopropanol (12.5 ml) and the reaction mixture is stirred for 2 h at 25°C. The reaction mixture is evaporated to dryness and the crude product is crystallized twice from diethylether to yield an off-white solid. Yield: 1.44 g (107.2 %), ESI-MS: m/z = 297 [M+H]+, Cl-Pattern Step 4: (3RAR)-4-(4-Chloro-phehylcarbamdyl)-l-methanesulfonyl-p)n^ carboxylic add ethyl ester 39d Compound 39c (1.44 g; 4.32 mmol) is dissolved in acetonitrile (10 ml) under addition of N,N-diisopropyl ethyl amine (2200 jxl; 12.96 mmol). Methanesulfonylchloride (990 mg; 8.64 mmol) is added and the mixture is stirred for 18 h at 25 °C. The reaction mixture is evaporated to dryness and purified with silica gel chromatography Yield: 0.895 g (55.3 %), ESI-MS: m/z = 375 [M+H]+, Cl-pattern Step 5: (3Ri4R)-4'(4'Chloro'phenylcarbamoyiyi-methanesulfonyl'pyn^ carboxylic add 39e Compound 39d (0.9 g; 2.4 mmol) is dissolved in a mixture of 1,4-dioxane/water (1:1; 15 ml). LiOH monohydxate (0.302 g; 7.2 mmol) is added as a solid and the mixture is stirred for 18 at 25 °C. The mixture is evaporated to dryness and dissolved in ethyl acetate and the product is extracted with saturated aqueous Na2CC>3 solution. The aqueous phase is cooled to 10 °C and acidified with 25% aqueous HCl solution until pH = 1. The product is extracted several times with ethylacetate (3 x 100 ml). The combined organic phases are washed with brine and dried over Na^SO*. After filtration the organic phase is evaporated to dryness. Yield: 0.7 g (84.1 %), ESI-MS: m/z = 345 [M-H]", Cl-pattern Step 6: l~(4~Amino-3~fluoro-phenyl)~3-methox)>-lH-p)nidin-2~one 39f Compound 40f is prepared as described for compound le. ESI-MS: m/z = 345 [M-H]- Step 7: (3R,4R)-l-Metha7iesulfonyl-p)rrolidine-3}4~dicarboxylic acid 3~[(4-chloro-phenyl)-amide] 4'{[2-fluorO'4-(3'methoxy-2-oxO'2H'pyridm'l'yl)'phenyl]'amide} 39g Compound 39e (80 mg; 0.23 mmol) is suspended in acetonitrile (1 ml) and N,N-diisopropyl ethyl amin (47 jil; 0.277 mmol) is added at 25 °C. BOP-C1 (70.5 mg; 0.277 mmol) is added as a solid and after stirring for 30 min at 25°C l-(4-amino-3-fluoro-phenyl)-3-methoxy-lH-pyridin-2-one (53.9 mg; 0.23 mmol) is added to the reaction mixture. The mixture is stirred for 3 d at 25°C, evaporated to dryness and purified by preparative HPLG Yield: 1.9 mg (1.5 %), ESI-MS: m/z = 562 [M+H]+ Example 40 (3R,4R)-l-Metiianestilfonyl-pyrrolidine-3>4-dicarboxylic acid 3-[(4-chloro phenyl)-amide] 4-{[2,6-difluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 40 and l-(4-Amino-375-difluoro-phenyl)-3-methoxy-lH-pyridin-2-one were prepared according to the methods described for example 39. ESI-MS: xn/z = 550 [M+H]+ Example 41 (3R>4R)-1 -Methanesulfonyl-pyrrolidine-S^-dicafboxylic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(6-oxo-6H-pyridazin-1 -yl)-phenyl]-amide} The compound of example 41 and 2"(4-amino-3-fluoro-phenyl)-2H-pyridazin-3-one were prepared according to the methods described for example 39. ESI-MS: m/z = 533[M+H]+ Example 42 (3R,4R)- l-Methanesulfonyl-pyrrolidine-S^-dicarboxylic acid 3- [ (4-chloro-phenyl)-amide] 4-{[2-fIuoro-4-(2-oxo-piperidin-l-yl)-phenyl]-amide} The compound of example 42 and l-(4-atnino-3-fluoro-phenyl)-piperidin-2-one were prepared according to the methods described for example 39. ESI-MS: m/z = 536 [M+H]+, Cl-pattern Example 43 (3R,4R)-l-Metiianesiilfon7l-pyrroHdine-3)4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-[(3-fluoro-4-morpholin-4-yl-phenyi)-amide] The compound of example 43 was prepared according to the methods described for example 39. 3-fluoro-4-morpholin-4-yl-phenylamine is commercially available. ESI-MS: m/z = 525 [M+H]+, Cl-pattern Example 44 (3R,4R)-l-Methanesulfonyl-pyrrolidine-3)4-dicarbox)rlic acid 3-[(4-chloro~ phenyi)-amide] 4-{[3-fluoro-4"(2-methyl-imidazol-l-yl)-phenyl]-amide} The compound of example 44 and 3-fluoro-4-(2-methyl-imidazol-l-yl)-phenylamine (CAS 209960-27-0) were prepared according to the methods described for example 39. ESI-MS: m/z = 519 [M+H]+, Cl-pattern Example 45 (3R,4R)- l-Methanesulfonyl-pyrrolidine-354-dicarboxylic acid 3- [ (4-chloro-phenyl)-amide] 4-[(3-£luoro-4- [ 1,2,4]triazol-1 -yl-phenyl)-hydroxy-amide] The compound of example 45 was prepared according to the methods described for example 39. N-(3-Fluoro-4-[l>2)4]triazol-l-yl-phenyl)-hydrox5damine is prepared according to CAS: 181997-13-7. ESI-MS: m/z = 523 [M+H]+> Cl-pattern Example 46 (3R,4R)-l-Methanesulfonyl-pyrrolidine-3>4-dicarboxylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridm-l-yl)-phenyl]-aimde}4^ The compound of example 46 was prepared according to the methods described for example 28. ESI-MS: m/z = 543 [M+Hf Example 47 (3R,4R)-l-Metiianesiilfonyl-pyrrolidine-3)4«dicarbosylic acid 3-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} 4-[(4-trifluoromethoxy-phenyl)-axnide] The compound of example 47 was prepared according to the methods described for example 28. ESI-MS: m/z = 583 [M+Hf Example 48 (SR^^-l-Metianesulfonyl-pyrrolidiae-S^dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(2-oxo-2H-pyridin-l-yl)-phenyi]-amide} The compound of example 48 was prepared according to the methods described for example 40. ESI-MS: m/z = 514 [M+H]+ Example 49 (3R>4R)-l-Cyclopropylmethyl--p^Trolidine-3)4-dicarbox}rlic acid 3-[ (4-chloro-phenyL)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 49 was prepared according to the methods described for example 24. ESI-MS: m/z = 508 [M+H]+ Example 50 (3R,4R)-l-MethanesiiIfonyl-pyrrolidine-3,4-dicarbo2ylic acid 3-[(4~chloro-phenyl)-amide] 4-[(3-fluoro-2!-methylsulfanyl-biphenyl-4-yI)-amide] The compound of example 50 was prepared according to the methods described for example 7 using compound CAS 209732-08-1 as amine. ESI-MS: m/z = 562 [M+H]+ Example 51 (3R>4R)-l-Methanesulfonyl-p}Trolidine-3)4-dicarboxylic acid 3-[(2!-fert-butylsulfamoyl-3-fluoro--biphenyl-4-yl)-ainide] 4- [(4~chloro-phenyl)-amide] The compound of example 51 was prepared according to the methods described for example 7 using CAS 209919-51-7 as amine. ESI-MS: m/z = 651 [M+H]+ Example 52 (3R,4R)-l-Meiiianesulfonyl-pyrroUdine-3,4-dicarboxylic acid 3-[(4-chloro- phenyl)-amide] 4-{[5-(2-ine&anesulfonyl-phenyI)-pyridm-2-yl]-ainide} The compound of example 52 was prepared according to the methods described for example 7 using compound CAS 793650-93-8 as amine. ESI-MS: m/z = 577 [M+H]+ Example 53 (3R,4R)-l-Methanesuifonyi-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(3-methyl-2-oxo-2H-pyridin-l-yl)-phenyI]-amide} The compound of example 53 was prepared according to the methods described for example 7. ESI-MS: m/z = 547 [M+H]+ Example 54 (3R,4R)-l-Metiianesuifon7l-pyrroHdine-3,4-dicarboxyiic acid 3-[(4~chloro-phenyl)-amide] 4-[(3-fluoro-2'-metlianesiilfonyl-biplieiiyi-4-7l)-anude] The compound of example 54 was prepared by oxidation of the compound of example 50. The compound of example 50 (39.53 mg; 0.07 mmol) is dissolved in ethyl acetate (2 ml) at 25 °C. To this solution mCPBA (30.34 mg; 2.5 equivalents) is added slowly and the mixture is stirred at 25 °C for 18 h. Purification with prep. HPLC. Yield: 8.15 mg (19.6%). ESI-MS: m/z = 594 [M+H]+ Example 55 (3R)4R)-3-(5-CMoro-pyridin-2-ylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l> yl)-phenylcarbamoyl]-pyrrolidine-l-carbox5rlic acid tert-butyl ester 2-Chloro-5-aminopyridine (3.258 g; 25 mmol) is dissolved in toluene (100 ml) under argon atmosphere. Within 10 min a solution of AlMe3 in toluene (2N> 12.8 ml) is added slowly. The mixture is stirred for 1 h at 25 °C. Compound 28b (10 g, 21 mmol) is added in one portion and the reaction mixture is heated under reflux for 2h. The obtained yellow suspension is cooled to 25 °C and diluted with THF (35 ml). For hydrolysis acetic acid (4.8 ml) is added and the suspension is stirred for 18 h. The obtained precipitate is filtered off, washed with toluene and TBME and dried in vacuo. Yield: 8.46 g (72%). ESI-MS: m/z = 556 [M+H]+ Example 56 (3R>4R)-l«Ethanesulfonyl-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin- 2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 56 was prepared according to the methods described for example 7 starting from compound of example 55. ESI-MS: m/z = 547 [M+H] + Example 57 (3R)4R)-l-(2>2-Difluoroeth7l)-p)rrrolidine-3>4-dicarbo^lic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4~(2-oxo-2H-pyridin-l-yl)-phenyl]-ainide} The compound of example 57 is prepared according to the methods described for example 24 with the exception of step 3 and step 4: Step 3: (3R,4R)-pyrrolidine-334-dicarboxylic acid 3-[(5-chlorop)nidin-2-yl)-amide] 4~ {[2-fluoro-4~(2~oxo-2H-pyridin-l-yl)-phenyl]-amide} (compound 57a) The compound of example 55 (8.4 g; 15 mmol) is suspended in dioxane (50 ml) and 4N HC1 in dioxane is added (50 ml). After stirring at 25 °C for 50 min Boc-deavage is completed. The mixture is diluted with THF and neutralized with aqueous Na2CO3-solution. The free base (3R,4R)-p}aroBdine-3,4-dicarboxylic acid 3-[(5-chloropyxidin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyi]-amide} is extracted several times with THF/dichloroxnethane (1:1 vol). The organic phase is washed with saturated aqueous NaCl-solution> dried over Na2SO4 and evaporated to dryness to yield 4.1 g (59.5 %) of compound 57a. ESI-MS: m/z = ■ 455[M+H]+ Step 4: (3R}4R)'l'(2>2-Difluoroethyl)'p}rrolidiii€-3>4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4- {[2-fluoro-4- (2-oxo~2H-pyridin-1 -yl)-phenyl]-amide} Compound 57a (0.41 g; 0.9 mmol) is dissolved in dichloromethane (4 ml) and DIEA (0.233 ml) is added. To this mixture trifluoro-methanesulfonic acid 2>2-difluoro-ethyl ester (0.338 mg; 1.6 mmol), dissolved in 1 ml dichloromethane, is added in one portion. The mixture is stirred at 25 °C for 72 h. The organic phase is then washed with aqueous ammonium acetate and NaCl solution, dried over Na2SO4 and evaporated to dryness. The crude product is purified by flash chromatography over SiO2- Yield: 0.299 g (63.8 %). ESI-MS: m/z = 519 [M+H]+ Example 58 (3R,4R)-l-Methanesulfonyl-pyrrolidine-3?4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-(l,l-dioxo-[l,2]thia2inan-2-yl)-phenyl]-ainide} The compound of example 58 was prepared according to the methods described for example 7 with the amine CAS 37441-49-9. ESI-MS: m/z = 555 [M-f-H]+ Example 59 (3R,4R)-l-MethanesiilfonyI-pyrroUdiiie-3,4-dicarbox7lic acid 3-[(4-chloro-phenyl)-amide] 4-{[4-( 1 >l-dioxo-isothiazolidin-2-yI)-phenyI]-amide} The compound of example 59 was prepared according to the methods described for example 7 with the amine CAS 90556-91-5. ESI-MS: m/z = 541 [M-hH]+ Example 60 (3R,4R)-l-MetiiaBesulfonyl-pyrroHdine-34-dicarboxylic add 3-[(4-chloro-phenyl)-amide] 4-{[2-methyl-4-(2-oxo-2H-pyridin-l~yl)-phenyl]-amide} The compound of example 60 was prepared according to the methods described for example 7 with the amine, l-(4-amino-3-methyl-phenyl)-lH-pyridin-2-one. ESI-MS: m/z = 529 [M+H]+ Example 61 (3R>4R)-l-MetiianesxiIfonyl-pyrrolidine-3>4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fiuoro-4-(3-oxo-morphoIin-4-yl)-phenyl]-amide} The compound of example 61 was prepared according to the methods described for example 7 with CAS 742073-22-9. ESI-MS: m/z = 539 [M+H]+ Example 62 (3R>4R)-l-Isopropyl-pyrrolidine-3)4-dicarboxyIic acid 3-[(5-dJoro-pyridin-2-yl)-amide] 4- {[2-fluoro-4- (2-oxo-2H-pyridin-1 -yl)-phenyl] - amide} The compound of example 62 was prepared according to the methods described for example 27. ESI-MS: m/z = 498 [M+H]+ Example 63 (3R,4R)-l-(4-Fluoro-benzyl)»pyrrolidine-3)4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2If-pyridin-l-yl)-phenyI]-amide} The compound of example 63 was prepared according to the methods described for example 27. ESI-MS: m/z = 563 [M+H]+ Example 64 (3R54R)-l-Metianesulfonyl-pyrroHdine«354-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-[(2-oxO"2H-[l,3!3bipyridinyl»6T-yl)-amide] The compound of example 64 was prepared according to the methods described for example 7 with the amine CAS 536747-63-4. ESI-MS: m/z = 516 [M+H]+ Example 65 (3R,4R)-l-Pyridin-2-ylmetiiyl-pyrrolidine-3,4-dicaTboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 65 was prepared according to the methods described for example 27. ESI-MS: m/z = 546 [M+H]+ Example 66 (S^^-l-Pyridin-S-ylmethyl-pyrroHdine-Sj^dicarboxyiic add 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyi]-amide} The compound of example 66 was prepared according to the methods described for example 27. ESI-MS: m/z = 546 [M+H]+ Example 67 (3R,4R)-l-Pyridin-4-ylinethyl-pyrrolidine-3,4"dicarboxylic acid 3-[(4-chloro- phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridiii-l-yI)-phenyl]-amide} The compound of example 67 was prepared according to the methods described for example 27. ESI-MS: m/z = 546 [M+H]+ Example 68 (3R,4R)-l-(2-Methoxy-ethyI)-pyrrolidine-3,4-dicarboxyKc acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 68 was prepared according to the methods described for example 24. ESI-MS: m/z = 513 [M+H]+ Example 69 (3R,4R)"l-(2-Fluoro-l-methyl-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H»pyridin-l-yl)-phenyl]-amide} The compound of example 69 was prepared according to the methods described for example 27. ESI-MS: m/z = 515 [M+H]+ Example 70 3-{(3R)4R)-3-(4-CUoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrrolidin-l-yl}-propionic acid methyl ester The compound of example 70 was prepared according to the methods described for example 24. ESI-MS: m/z = 541 [M+H]+ Example 71 (3R>4R)-l-(3-Huoro-oxeten-3*ylme1^yi)-pyrrolidine-3,4-dicarbox7lic acid 3-[(4-chioro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2ii-pyridin-l~yl)-pherxyI]-ainide} The compound of example 71 was prepared according to the methods described for example 24 using 3-bromomethyl-3-fluoro-oxetane (compound 71 e) as alkylating agent ESI-MS: m/z = 543 [M+H]+ Synthesis of3-bromomethyl-3-fluoro-oxetane: a) 3-Benz)4oxy-2-methylene-l-propanol 71a: 2-Methylene-propane-l>3-diol (2.2 g; 24.96 nunol)and dibutyltin oxide (6.85 g; 27.96 mmol) were refluxed in chloroform/ methanol (100 ml 10:1) for 24 h to obtain a clear solution. The solvent was removed under reduced pressure to give the starmoxane derivative as a white solid. Cesium fluoride (7.25 g; 47.7 mmol) was added and the mixture was dried under high vacuum. To this reaction mixture, DMF (20 ml) and benzyl bromide (3.27 ml; 27.5 mmol) were added and the reaction mixture was stirred for 24 h at 25 °C. After that, the reaction mixture was heated at 50 °C for 1 h. The mixture is cooled to 25 °C and diluted with ethyl acetate (100 ml) and water (2 ml). The reaction mixture is stirred vigorously for 30 min and then filtered through a pad of celite to remove dibutyltin oxide. The filtrate was washed with water and then with brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography eluting with 20 % ethyl acetate/hexane to yield 2.6 g (60%) compound 71a) as oil. *H-NMR (CDC13): 5 7.36 - 7.28 (m, 5H)> 5.20 (s, 1H), 5.15 (s, 1H)> 4.51 (s, 2H), 4.19 (s,2H), 4.10 (s,2H). b) 3-Bromo-2-fluoro-2-(ben2yloxymethyl)propan-l-ol 71 b: A solution of 71 a) (3.9 g; 21.91 mmol) and triethylamine 3HF complex (5.29 g; 5.35 ml; 32.86 mmol) in dichloromethane (100 ml) was treated with NBS (4.28 g; 24.1 mmol) portion wise at -10 °C and stirred for 17 h. Subsequently the mixture was poured into ice-water (100 ml) and neutralized with 25% aqueous ammonia. The organic layer was separated, washed with 0.1 N HC1, followed by 5 % aqueous NaHCO3, dried and evaporated to dryness. The crude material was purified by silica gel chromatography (15 % ethyl acetate/hexane) to give 2.54 g (42%) of 71 b. :H-NMR (CDC13): 5 7.37 - 7.30 (m, 5H), 4.58 (s, 2H), 3.89 - 3.63 (m, 6H), GC~ MS: 276 (M*). c) 3-Fluoro-3-(benzyloxymethyl)oxetane 71 c: A mixture of 71 b (10 g; 36.10 mmol) and potassium carbonate (29.9 g; 216.9 mmol)) in dry acetonitrile (200 ml) is refluxed for 72 h. After that the reaction mixture is extracted with ethyl acetate, washed with brine, dried over Na2SC>4 and purified by silica gel column chromatography (10% ethyl acetate/hexane) to give 2.12 g (30%) of 71c. *H-NMR (CDCU): 6 7.38 - 7.30 (m, 5H), 4.77 (dd> 2H), 458 (dd, 2H), 3.81 (s, 1H), 3.76 (s, 1H), GC-MS: 196 (M+). d) 3-Fluoro-3-(hydroxymethyl)oxetane 71 d: A solution of 71 c (1.1 g; 5.61 mmol) in EtOH (10 ml) containing Pd/C (200 mg, 10%) and acetic acid (1 ml) was stirred for 24 h under hydrogen atmosphere (40 psi). The catalyst was filtered off and the filtrate was concentrated under reduced pressure to give compound 71 d (410 mg; 70%). ^-NMR (CDC13): 5 4.77 (dd, 2H), 4.57 (dd, 2H), 3.98 (s, 1H), 3.93 (s, 1H). e) 3-Bromomethyl~3-fluoro-oxetane 71 e: To a stirred solution of compound 71 d (500 mg; 4.72 mmol) CBr4 (1.95 g; 5.89 mmol) in dichloromethane (7 ml) was added portion "wise triphenylphosphine (1.85 g; 7.07 mmol) at 0 °C. After complete addition, the reaction mixture was stirred for additional 2 h, diluted with pentane and washed with 5% aq NaHCO3, brine and dried over Na2SC>4 .The solvent was removed under atmospheric pressure to give compound 71 e (406 mg, 51%). aH-NMR (CDCI3): 6 4.79 (dd, 2H), 4.56 (dd, 2H), 3.78 (s, 1H), 3.73 (s, 1H). Example 72 2-{(3R,4R)-3-(4'CUoro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenylcarbamoyl]-pyrroUdin-l-ylmethyl}-cyclopropanecarboxylic acid ethyl ester The compound of example 72 was prepared according to the methods described for example 24. ESI-MS: m/z = 581 [M+H]+ Example 73 (3R34R)-l-Thiophen-2-yimethyl-pyrrolidine-3,4-dicarboxyiic acid 3- [(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yI)-phenyl]-amide} The compound of example 73 was prepared according to the methods described for example 27. ESI-MS: m/z = 551 [M+H]+ Example 74 (3R,4R)-l-TMophen-3-ylme^ acid 3-[(4-chloro- phenyl)-amide] 4- {[2~fluoro-4-(2-oxo-2i?-pyridin-1 -yl)-phenyl] -amide} The compound of example 74 was prepared according to the methods described for example 27. ESI-MS: m/z = 551 [M+H]+ Example 75 (3R,4R)-l-Cyanomethy]-pyrrolidine-3?4-dicarboxylic acid 3-[(4-chloro-phenyl)-amide] 4-{[2-fluoro-4-(2-oxo"2H-p^idin-l-yl)"phenyl]-amide} The compound of example 75 was prepared according to the methods described for example 24. ESI-MS: m/z = 494 [M+H]+ Example 76 (3R,4R)-l-Metiiyl-pyrrolidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyl)-methyl-amide] 4*{[2-fluoro*4-(2-oxo-2H-pyridin-l-yl)-phenyl]-methyl-amide} The compound of example 76 was prepared according to the methods described for example 24. ESI-MS: m/z = 494 [M-f H]+ Example 77 (3R,4R)-l-(2-Tetra^ol-l-yl-acetyI)-pyrrolidine-3,4-dicarboxylic acid 3-[(4-diloro-phenyI)-amide]4-{[2'fluoro-4-(2-oxo-2iJ-pyridin-l-yl)-phenyl]-ainide} The compound of example 77 was prepared according to the methods-described for example 13. ESI-MS: m/z = 565 [M+H]+ Example 78 (3RJ4R)-l-(2-lH-Tetrazol-5"yl-acetyl)-pyrrolidine-3,4-dicarbo^Uc acid 3-[(4-chloro-phenyl) - amide] 4- {[2-fluoro-4- (2-oxo-2H-pyridin-1 -yl) -phenyl] - amide} The compound of example 78 was prepared according to the methods described for example 13. ESI-MS: m/z = 565 [M+H]+ Example 79 (3R,4R)-l-(2,2-Difluoro-ethyI)«pyrroIidine-3,4-dicarboxylic acid 3-[(6-chloro-pyridazin-3-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2i?-pyridin-l-yl)-phenyl]-amide} The compound of example 79 was prepared according to the methods described for example 57. ESI-MS: m/z = 521 [M-f-H]+ Example 80 (3R>4R)-l-(2,2-Difluoro-etiy])-pyrrolidine»3,4-dicarboxylic acid 3-[(5-chloro-pyrimidin-2-yI)-amide] 4-{[2-fIuoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 80 was prepared according to the methods described for example 57. ESI-MS: m/z = 521 [M+H]+ Example 81 (3R54R)-l-(2,2-Difluoro-eth7l).pyrrolidine-3,4-dicarbox^Kc acid 3-[(5-chIoro-thiophen-2-yL)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 81 was prepared according to the methods described for example 57. ESI-MS: m/z = 525 [M+H]+ Example 82 (3R,4R)-l-Methanesidfon)i-pyn-olidine-3,4-dicarboxylic acid 3-[(4-chloro-phenyi)-amide] 4-{ [4-{3-oxo-moi^holin-4-yl)-phenyl] -amide} The compound of example 82 was prepared according to the methods described for example 7 using as amine CAS 438056-69-0. ESI-MS: m/z = 521 [M+H]+ Example 83 (3R>4R)*3-(5-CWoro-pyridin-2-ylcarbamoyl)-4"[2-fluoro-4-(2-oxo-2H-pyridiii-l-yl)-phenylcafbamoyl]-pyrrolidine-l-carboxylic add methyl ester The compound of example 83 was prepared according to the methods described for example 57 and 14. ESI-MS: m/z = 514 [M+H]+ Example 84 (3R,4R)-l-Trifluoromethyl-pyrrolidine-3)4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-l-yl)-phenyl]-amide} The compound of example 84 was prepared according to the methods described for example 57. ESI-MS: m/z = 524 [M+H]+ Example 85 (3R,4R)-l-(2>2,2-Trifluoro-ethyl)-p}Trolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-aniide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin"l-yl)-phenyl]-amide} The compound of example 85 was prepared according to the methods described for example 57. ESI-MS: m/z = 538 [M+H]+ Example A Film coated tablets containing the following ingredients can be manufactured in a conventional manner: Ingredients Per tablet Kernel: Compound of formula (I) 10.0 mg 200.0 mg Microcrystalline cellulose 23.5 mg 43.5 mg Lactose hydrous 60.0 mg 70.0 mg Povidone K30 12.5 mg 15.0 mg Sodium starch glycolate 12.5 mg 17.0 mg Magnesium stearate 1.5 mg 4.5 mg (Kernel Weight) 120.0 mg 350.0 mg Film Coat Hydroxypropyl methyl cellulose 3.5 mg 7.0 mg Polyethylene glycol 6000 0.8 mg 1.6 mg Talc 1.3 mg 2.6 mg Iron oxyde (yellow) 0.8 mg 1.6 mg Titan dioxide 0.8 mg 1.6 mg The active ingredient is sieved and mixed with rnicrocristalline cellulose and the mixture is granulated with a solution of polyvinylpyrrolidon in water. The granulate is mixed with sodium starch glycolate and magesiumstearate and compressed to yield kernels of 120 or 350 mg respectively. The kernels are lacquered with an aqueous solution / suspension of the above mentioned film coat. Example B Capsules containing the following ingredients can be manufactured in a conventional manner: Ingredients Per capsule Compound of formula (I) 25.0 mg Lactose 150.0 mg Maize starch 20.0 mg Talc 5.0 mg The components are sieved and mixed and filled into capsules of size 2. Example C Injection solutions can have the following composition: Compound of formula (I) 3.0 mg Polyethylene Glycol 400 150.0 mg Acetic Acid - ■ q.s. ad pH 5.0 Water for injection solutions ad 1.0 ml The active ingredient is dissolved in a mixture of Polyethylene Glycol 400 and water for injection (part). The pH is adjusted to 5.0 by Acetic Acid. The volume is adjusted to 1.0 ml by addition of the residual amount of water. The solution is filtered, filled into vials using an appropriate overage and sterilized. Example D Soft gelatin capsules containing the following ingredients can be manufactured in a conventional manner: Capsule contents Compound of formula (I) 5.0 mg Yellow wax 8.0 mg Hydrogenated Soya bean oil 8.0 mg Partially hydrogenated plant oils 34.0 mg Soya bean oil 110.0 mg Weight of capsule contents 165.0 mg Gelatin capsule Gelatin 75.0 mg Glycerol 85 % 32.0 mg Karion 83 8.0 mg (dry matter) Titan dioxide 0.4 mg Iron oxide yellow 1.1 mg The active ingredient is dissolved in a warm melting of the other ingredients and the mixture is filled into soft gelatin capsules of appropriate size. The filled soft gelatin capsules are treated according to the usual procedures. Example E Sachets containing the following ingredients can be manufactured in a conventional manner: Compound of formula (I) 50.0 mg Lactose, fine powder 1015.0 mg Microcristalline cellulose (AVICEL PH 102) 1400.0 mg Sodium cafboxymethyl cellulose 14.0 mg Polyvinylpyrrolidon K 30 10.0 mg Magnesiumstearate 10.0 mg Flavoring additives 1.0 mg The active ingredient is mixed with lactose, microcristalline cellulose and sodium carboxymethyl cellulose and granulated "with a mixture of polyvinylpyrrolidon in water. The granulate is mixed with magnesiumstearate and the flavouring additives and filled into sachets.

Documents:

3504-CHENP-2006 AMENDED PAGES OF SPECIFICATION 05-10-2012.pdf

3504-CHENP-2006 AMENDED CLAIMS 05-10-2012.pdf

3504-CHENP-2006 CORRESPONDENCE OTHERS 16-12-2011.pdf

3504-CHENP-2006 EXAMINATION REPORT REPLY RECEIVED 05-10-2012.pdf

3504-CHENP-2006 OTHER PATENT DOCUMENT 05-10-2012.pdf

3504-CHENP-2006 POWER OF ATTORNEY 05-10-2012.pdf

3504-CHENP-2006 FORM-3 05-10-2012.pdf

3504-chenp-2006-abstract.pdf

3504-chenp-2006-claims.pdf

3504-chenp-2006-correspondnece-others.pdf

3504-chenp-2006-description(complete).pdf

3504-chenp-2006-form 1.pdf

3504-chenp-2006-form 26.pdf

3504-chenp-2006-form 3.pdf

3504-chenp-2006-form 5.pdf

3504-chenp-2006-pct.pdf