Title of Invention	A HETEROCYCLIC AMIDE COMPOUND AND A PROCESS FOR PREPARATION THEREOF
Abstract	The present invention relates to a heterocyclic amide compound of formula (I) or a pharmaceutical acceptable salt thereof or an acylated, alkylated, or phosphorylated form of the compound and a pharmaceutically acceptable carrier

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DPP-IV inhibitors The present invention relates to a novel class of dipeptidyl peptidase inhibitors, including pharmaceutically acceptable salts and prodrugs thereof, which are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes mellitus, often referred to as non-insulin dependent diabetes meKtus (NIDDM), and of conditions that are often associated with this disease, such as obesity and lipid disorders. The invention also relates to a process for the preparation of such inhibitors. Diabetes refers to a disease process derived from multiple causative factors and characterized by elevated levels of plasma glucose or hyperglycemia in the fasting state or after administration of glucose during an oral glucose tolerance test Persistent or uncontrolled hyperglycemia is associated with increased and premature morbidity and mortality. Often abnormal glucose homeostasis is associated both directly and indirectly with alterations of the lipki, Kpoprotein and apolipoprotetn metabolism and other metabolic and hemodynamic disease. Therefore patients with Type 2 diabetes mellitus are at an increased risk of macrovascular and microvascular complications, including coronary heart disease, stroke, peripheral vascular disease, hypertension, nephropathy, neuropathy, and retfnopathy. Therefore, therapeutical control of glucose homeostasis, lipid metabolism and hypertension are critically important in the clinical management and treatment of diabetes mellitus. There are two generally recognized forms of diabetes. In Type 1, or insulin-dependent, diabetes mellitus (IDDM), patients produce little or no insulin, which is the hormone regulating glucose utilization. In Type 2, or noninsulin dependent, diabetes mellitus (NIDDM), patients often have plasma insulin levels that are the same or elevated compared to nondiabetic subjects. These patients develop a resistance to the insulin stimulating effect on glucose and lipid metabolism in the main insulin-sensitive tissues, namely the muscle, liver and adipose tissues. Further, the plasma insulin levels, while elevated, are insufficient to overcome the pronounced insulin resistance. Insulin resistance is not primarily due to a diminished number of insulin receptors but to a post-insulin receptor binding defect that is not yet understood. This resistance to insulin responsiveness results in insufficient insulin activation of glucose uptake, oxidation and storage in muscle, and inadequate insulin repression of lipolysis in adipose tissue and of glucose production and secretion in the liver. The available treatments for Type 2 diabetes, which have not changed substantially in many years, have recognized limitations. While physical exercise and reductions in dietary intake of calories will dramatically improve the diabetic condition, compliance with this treatment is very poor because of well-entrenched sedentary lifestyles and excess food consumption, especially of foods containing high amounts of saturated fat. Increasing the plasma level of insulin by administration of sutfonylureas (e.g., tolbutamide and glipizide) or meglitinide, which stimulate the pancreatic p-cells to secrete more insulin, and/or by injection of insulin when sulfbnylureas or meglitinide become ineffective, can result in insulin concentrations high enough to stimulate the very insulin-resistant tissues. However, dangerously low levels of plasma glucose can result from administration of insulin or insulin secretagogues (sulfonylureas or meglitinide). and an increased level of insulin resistance, due to the even higher plasma insulin levels, can occur. The biguanktes increase insulin sensitivity resulting in some correction of hyperglycemia. However, the two biguarmtes, phenfbrmin and metfonmin, can induce lactic acklosis and nausea/tfiarrhoea. Metfonmin has fewer side effects than phenformin and is often prescribed for the treatment of Type 2 diabetes. The glitazones (/.a, 5-benzytthiazo6dine-2,4-dk>nes) are a recently described class of compounds with potential for ameliorating many symptoms of Type 2 diabetes. These agents substantially increase insulin sensitivity in muscle, liver and adipose tissue in several animal models of Type 2 diabetes, resulting in partial or complete correction of the elevated plasma levels of glucose without occurrence of hypoglycemia. The glitazones that are currently marketed are agonists of the peroxisome proliferator activated receptor (PPAR), primarily the PPAR-gamma subtype. PPAR-gamma agonism is generally believed to be responsible for the improved insulin sensitization that is observed with the glitazones. Newer PPAR agonists that are being tested for treatment of Type 2 diabetes are agonists of the alpha, gamma or delta subtype, or a combination of these, and in many cases are chemically different from the glitazones (/.©., they are not thiazolidinediones). Serious side effects (e.g., liver toxicity) have occurred with some of the glitazones, such as troglitazone. Additional methods of treating the disease are still under investigation. New biochemical approaches that have been recently introduced or are still under development include treatment with alpha-glucosidase inhibitors (e.g., acarbose) and protein tyrosine phosphatase-IB (PTP-1B) inhibitors. Compounds that are inhibitors of the dipeptidyl peptidase-IV (DPP-IV) enzyme are also under investigation as drugs that may be useful in the treatment of diabetes, and particularly Type 2 diabetes. See for example WO-A-97/40832, WO-A-98/19998, WO-A-03/180 and WOA-03/181. The usefulness of DPP-IV inhibitors in the treatment of Type 2 diabetes is based on the fact that DPP-IV in vivo readily inactivates glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). GLP-1 and GIP are incretins and are produced when food is consumed. The incretins stimulate production of insulin. Inhibition of DPP-IV leads to decreased inactivation of the incretins, and this in turn results in increased effectiveness of the incretins in stimulating production of insulin by the pancreas. DPP-IV inhibition therefore results in an increased level of serum insulin. Advantageously, since the incretins are produced by the body only when food is consumed. DPP-IV inhibition is not expected to increase the level of insulin at inappropriate times, such as between meals, which can lead to excessively low blood sugar (hypoglycemia). Inhtortion of DPP-IV is therefore expected to increase insulin without increasing the risk of hypoglycemia, which is a dangerous side effect associated with the use of insulin secretagogues. DPP-IV inhibitors may also have other therapeutic utilities, as discussed elsewhere in this application. DPP-IV inhibitors have not been studied extensively to date, especially for utilities other than diabetes. New compounds are needed so that improved DPP-IV inhibitors can be found for the treatment of diabetes and potentially other disease and conditions. Thus, the object of the present invention is to provide a new class of DPP-IV inhibitors which may be effective in the treatment of Type 2 diabetes and other DPP-IV modulated diseases. Accordingly, the present invention provides novel compounds of formula (I) as defined in the claims. Preferably, the present invention provides novel compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein Z is selected from the group consisting of phenyl; naphthyl; C3-7 cycloalkyl; heterocycte; and beterobicyde; wherein Z is optionally substituted with one, or independently from each other, more of halogen; CN; OH; =O, where the ring is at least partially saturated; c1_6 alkyl, optionally substituted with one or more F; and OC1_6 alkyl, optionally substituted with one or more F; R\ R2, R4, R5 are independently from each other selected from the group consisting of H; OH; C1-C6; alkyl, optionally substituted with one or more F; and O-C1-6 alkyl, optionally substituted with one or more F; and/or R1 and R2 optionally form together C3-.7 cycloalkyl, which is optionally substituted with one or more F; and/or R2 and R3 optionally form together C3-7 cycloalkyl, which is optionally substituted with one or more F; and/or R3 and R4 optionally form together C3.7 cycloalkyl, which is optionally substituted with one or more F; and/or R4 and R5 optionally form together C1-7 cycloalkyl, which is optionally substituted with one or more F; R3 is H or c1-4 alkyl; X is selected from the group consisting of H; F; and C1-4 alkyl, optionally substituted with one or more F; nisO, 1 or 2; A1, A2 are independently from each other selected from the group consisting of H; halogen; c1-c4 alkyl, optionally substituted with one or more F; and R6; provided that one of A1 and A2 is R6; R6 is -C(R7RVY-T; R7, R8 are independently from each other selected from the group consisting of H; F; and c1-c4 alkyl, optionally substituted with one or more F; and/or R7 and R8 optionally form together C3-7 cycloalkyl, which is optionally substituted with one or more F; Y is selected from the group consisting of -C1-c4 alkyl-O-; -N(R); -C1-4 alkyl-N(R9)--S-; -c1-4 alkyt-S-; -S(0)-; -C1-4 alkyl-S(O)-; -S(O)r-; and -c1-4 alkyl-S(O)r; wherein each C1-6 alkyl is optionally substituted with one or more F; R9, T are independently from each other T1-T2 orT2; T1 is selected from the group consisting of -C1-4 alkyl-; -C1-4 alkyl-O- -C1-4 alkyl-N(R10)- -C(O)-; -C(O)-C1-4 alkyJ-; -C(O)-C1-4 alkyl-O-; -C(O)-C1-4 alkyl-N(R10)-; -C(O); -C(O)O-C1-4 alkyl-; -0(0)0-c1-4 alky-o-; -C(O)O-C1-4 alkyl-N(R10)-; -C(O)N(R10)-; -C(O)N(R10)-C1-6 alkyl-; -C(O)N(R10)-C1-6 alkyl-O-; -C(O)N(R10)-C1-6 alkyl-N(R11)-; -S(O)2-; -S(O)rCu alkyl-; -S(O)z-C1-6 alkyl-O; and -S(0)2-C1-6 alkyl-N(R10)-; wherein each C1-.6 alkyl is optionally substituted with one or more F; R100, R11 are independently from each other H or c1-6 alkyl, optionally substituted with one or more F; T2 is selected from the group consisting of H; phenyt; naphthyl; wherein phenyl and naphthyl are optionally substituted with one, or independently from each other, more of halogen; CN; R12; COOH; OH; C(O)NH2; S(o)NHz; COOT3; OT3; C(O)NHT3; SfOfeNHT3; or T3; C3.7 cydoafcyl; heterocycte; and heterobicyde; wherein C3-7 cydoalkyl, heterocycte and heterobicycJe are optionally substituted with one, or independently from each other, more of halogen; CN; R13; OH; =O, where the ring is at least partially saturated; NH2 COOH; C(O)NH2; S(O)2NH2; COOT3; OT3; C(O)NHT3; S(O)2NHT3; NHT3;or T3; R12 is selected from the group consisting of C1-6 alkyl; O-C1-6 alkyl; COO-C1-6 alkyl; OC(O)- C1-6 alkyl; C(O)N(R15)- C1-6 alkyl; S(O)2N(R17)-C1-6 alkyl; S{O)-C1-6 alkyl; S(O)rC1-6 alkyl; and N(R18)S(O)rC-6 alkyl; wherein each C1-6 alkyl is optionally substituted with one, or independently from each other, more of F, COOR19, C(o)N(R20R21), S(O)N(R22R23), OR24, NfR^R26), T3. O-T3 or N(R27)-!3; R13 is selected from the group consisting of C1-4 alkyl; OC1-4 alkyl; N(R14)-C1-4alkyl; COOC1-6 alkyl; OC(O)- C« alkyl; C(O)N(R15)- C1-6 alkyl; N(R16)-C(O)-C1-6« alkyl; S(O)2N(R17)-C1-6 alkyl; S(O)-C1-6 alkyl; S(O)-C1-6 alkyl; and -N(R18)S(O)2-C6.6 alkyl; wherein each C1-6 alkyl is optionally substituted with one, or independently from each other, more of F, COOR19, C(O)R20R21), S(O)2N(R22R23), OR24,N(R25R26), T3, O-T3 or NCR27)-!3; R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27 are independently from each other H or C1-6 alkyl; T3 is selected from the group consisting of phenyl; naphthyl; wherein phenyl and naphthyl are optionally substituted with one, or independently from each other, more of halogen; CN; COOH; OH; C(O)NH2; S(O)2NH2; C1-6 alkyl; O-C1.6 alkyl; COO-C1.8 alkyl; 0C(O)- C1-6 alkyl; C(O)N(R28)- C1-6 alkyl; S(O)2N(R29)-C1-6 alkyl; S(O)2C1-6alkyl; or N(R30)S(O)2-C1-6alkyl; heterocycte; heterobicycle; and C3.7 cycloalkyl; wherein C3-7 cycloalkyl, heterocycle and heterobicycle are optionally substituted with one, or independently from each other, more of halogen; CN; OH; =0, where the ring is at least partially saturated; NH2 COOH; C(O)NH2; S(O)aNH2; C1-6 alkyl; O-C1-6 alkyl; NflO-Ct-a alkyl; COO-C1-6 alkyl; OC(O)- C1-6 alkyl; C(O)N(R32)- C1-6 alkyl; N(R33)-C(O)-C1-6 alkyl; SPh^R34)-C1-6 alkyl; S(O)2-C1-6 alkyl; or -N(R35)2S(O)2-C1-6 alkyl. Within the meaning of the present invention the terms are used as follows: "AlkyT means a straight-chain or branched carbon chain that may contain double or triple bonds. It is generally preferred that alkyl doesn't contain double or triple bonds. "C1-6 Alkyl" means an alkyl chain having 1-6 carbon atoms, e.g. methyl, ethyl, -CH=CH2l -CsCH, n-propyl, isopropyl, -CH=CH~CH3, -CH2~CH=CH2, n-butyi, isobutyt, -CH=CH-CH2-CH3, -CH=CH-CH=CH2, seo-btityl tert-butyl, n-pentane, n-hexane, or amidst, e.g. -CH2, -CHr-CH*-, -CH=CH-, -CH(CHa)-, -C(CH2)-, -CH2-CH2-CH2-, -CH^Hs)-, -CH(CH3)2-. Each hydrogen of a C^ alkyl carbon may be replaced by a substituent "C3-7 Cydoalkyl" means a cycfic alkyl chain having 3-7 carbon atoms, e.g. cydopropyl, cydobuty), cyclopentyl, cyclohexyl, cyctohexenyL, cyctoheptyi. Each hydrogen of a cydoalkyl carbon may be replaced by a substituent. "Halogen" means fluoro, chloro, bromo or iodo. It is generally preferred that halogen is fluoro or chloro. "Heterocycle" means a cyclopentane, cydohexane or cydoheptane ring that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or un-saturated) wherein at least one carbon atom up to 4 carbon atoms are replaced by a heteroatom selected from the group consisting of sulfur (induding -S(O)-, -S(O)r), oxygen and nitrogen (induding =N(O» and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom. Examples for a heterocycle are furah, thiophene, pyrrole, pyrroline, imidazole, imidazoline, pyrazole, pyrazoline, oxazole, oxazoline, isoxazole, isoxazoline, thiazole, thiazoline, isothrazole, isothiazoline, thiadiazole, thiadiazoline, tetrahydroftiran, tetrahydrothiophene, pyrrolidine, imidazolidine, pyrazolidine, oxazoiidine, isoxazolidine, thiazolidine, isothiazolidine, thiadiazolidine, sulfolane, pyran, dihydropyran, tetrahydropyran, imidazolidine, pyridine, pyridazine, pyrazine, pyrimidine, piperazine, piperidine, morpholine, tetrazole, triazole, triazolidine, tetrazolidine, azepine or homopiperazine. "Heterobicycle" means a heterocycle which is condensed with phenyl or an additional heterocycle to form a bicyclic ring system. "Condensed" to form a bicyclic ring means that two rings are attached to each other by sharing two ring atoms. Examples for a heterobicyde are indole, indoline, benzofuran, benzothiophene, benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, benzimidazole, benzimidazoline, quinoline, quinazoline, dihydroquinazoline, dihydroquinoline, isoquinoline, tetrahydroisoquinoline, dihydroisoquinollne, benzazepine, purine or pteridine. A preferred stereochemistry of compounds accorcfing to the present invention is shown in formula (la) Preferred compounds of formula (I) or (la) are those compounds in which one or more of the residues contained therein have the meanings given below, with all combinations of preferred substituent definitions being a subject of the present invention. With respect to all preferred compounds of the formulas (I) or (la) the present invention also includes all tautomeric and stereoisomeric forms and mixtures thereof in all ratios, and their pharmaceutically acceptable salts. In preferred embodiments of the present invention, the substituents R1 - R5, Z, X, n, A1 and A2 of the formula (I) or (la) independently from each other have the following meaning. Hence, one or more of the substituents R1 - R5, Z, X, n, A1 and A2 can have the preferred or more preferred meanings given below. Z is preferably is phenyl or heterocycte and Z is optionally substituted independently from each other with 1,2 or 3, more preferably up to 2 or 3, of Cl, F, CNf CH3 or OCH3. In one embodiment Z is substituted with up to 3 F. It is preferred that R\ R2, R4, R5 are independently from each other selected from the group consisting of H, F, OH CH3l OCH3. R3 is preferably H. X is preferably H, F or CH3. Preferably, n is 1. In other embodiments, n is 0 or 2. It is preferred that A1 is R6 and A2 is H, F or CH3. In this case, n is preferably 1 or 2. In other embodiments, in particular, when n is 0 or 2, A2 is preferably R6. In this case, A2 is preferably H, F orCHs. R6 is preferably -CIVY-T. Y is preferably -O-, -N(R*)- or -S(O)r. more preferably -O- or -NCR9)-. Preferably, R9 is selected from the group consisting of H, CH3, COOH, COOCH3, C(O)NH2, C(O)N(CH3)2, and SfC^CH* more preferably H. CH3, most preferably H. It is preferred that T is T1-T2 or T2, wherein T1 is selected from the group consisting of -CHa-; -C(Oh -c(O)-CHr; -C(O)O-; -C(O)O-CH2-; -C(O)NH-; -C(O)NH-CH2-; -S(O)2-; and -S(O)2-CH2-. More preferred is T1 selected from the group consisting of -C(O)-; -CIV; S(O)T-; and -C(O)NH-. It is preferred that T is T1-T2. In this case, V-T2 is preferably a group as defined below. In one embodiment, T1-T2 is preferably CHjrphenyl, whereby phenyl may be substituted with 1-3, preferably 1 or 2, substituents selected from halogen, CN, O-CM alkyl, C1-4 alkyl or S(O)2CH3, preferably F, Cl, OMe, Me or S(O)2CH3. In one embodiment, T1-T2 is preferably CH2-C3.7 cydoalkyl, more preferably cydopropyl or cydobutyl, more preferably cydopropyl, whereby cycloalkyl may be substituted with 1 or 2, preferably 1t of halogen; CN; OH; NH2 COOH; C(O)NH2; or S(O)2NH2 more preferably COOH or C(O)NH2, In one embodiment, T1-T2 is preferably C1-4 alkyl, preferably methyl, ethyl or propyl, most preferably methyl. In one embodiment, T1-T2 is preferably C(O)-phenyl, whereby phenyl may be substituted with 1-3, preferably 1 or 2, substituents selected from halogen, CN, O-C1-4 alkyl. C1-4 alkyl or S(O)2CH3 preferably F, Cl, OMe, Me orS(O)2CH3 In one embodiment, T1-T2 is preferably C(O)-C-7 cycloalkyl, more preferably cydopropyl or cydobutyl, more preferably cyctopropyl, whereby cycloalkyl may be substituted with 1-3, preferably 1 or 2f substituents selected from halogen, CN, O-CM alkyl, C1-4 alkyl, whereby alkyl may be further substituted with 1 to 3 F; more preferably cydoalkyl may be substituted with 1 C1-4 alkyl substituted with 1 to 3 F. In one embodiment, T1-T2 is preferably C(O)-heterocycle, whereby heterocycte may be substituted with 1-3, preferably 1 or 2, substituents selected from halogen, CN, OC1-4 alkyl, C1-4 alkyl or S(O)2CH3; preferably, the heterocyde is aromatic, more preferably containing 1 or 2 heteroatoms selected from N and O, most preferably N. In one embodiment, T1-T2 is preferably S(O)rphenyl( whereby phenyl may be substituted with 1-3, preferably 1 or 2, substituents selected from halogen, CN, O-C1-4 alky!, C1-4 alkyl or S(O)2CH3, preferably F, Cl, O-Met Me or S(O)2CH3. In one embodiment, T1-T2 is preferably S(O)2-C3-7 cycloalkyl, more preferably cydopropyl or cydobutyl, more preferably cyclopropyl, whereby cycloalkyl may be substituted with 1-3, preferably 1 or 2, substituents selected from halogen, CN, O-CM alkyl, C1-4 alkyl, whereby alkyl may be further substituted with 1 to 3 F; more preferably cycloalkyl may be substituted with 1 C^ alkyl substituted with 1 to 3 F. In one embodiment, T1-T2 is preferably S(O)2-C1-4 alkyl, preferably S(O)2CH3. In one embodiment, T1,T2 is preferably C(O>-NH-phenyl, whereby phenyl may be substituted with 1-3, preferably 1 or 2, substituents selected from halogen, CN, O-C1-4 alkyl, C1-4 alkyl or S(O)2CH3. When T is T2, is preferably a group as defined below. In one embodiment, T2 is preferably H. In one embodiment, T2 is preferably phenyl, whereby phenyl may be substituted with 1-3, preferably 1 or 2, substituents selected from halogen, CNt O-C1-4 alkyl, C1-4 alkyl or S(O)2CH3, preferably F, Cl, O-C1-4, Me or S(O)2CH3. In one embodiment, T2 is preferably heterocyde, whereby heterocyde may be substituted with 1-3, preferably 1 or 2, substituents selected from halogen, CN, phenyl, heterocyde, O-C1-4 alkyl, C1-4 alkyl orS(O)2CH3; preferably, the heterocyde is aromatic, more preferably containing 1, 2 or 3 heteroatoms selected from N and O, most preferably N. When the heterocyde is substituted with phenyl or heterocyde, the heterocyde is preferably aromatic, more preferably containing 1, 2 or 3 heteroatoms selected from N and O, most preferably N, and the phenyl or heterocycle may be further substituted by 1 or 2 F orS(O)2CH3. In one embodiment, T2 is preferably CF3. T2 is preferably phenyl or heterocycle. Preferably, R6 is -CHz-NKR36)-"!", wherein R36 is H, S(O)2CH3or S(O)2-C3-7 cydoalkyl, most preferably H. In other embodiments, R6 is -CH2-O-T. In the case that Y contains the group R9, the following is preferred in embodiments: When R9 is T1-T2 and represents -C1-4 alkyl and T is T1-T2 and represents -C1-6 alkyl then R9 and T may form together a 3 to 7 membered cydic group containing 1 N, preferably a 5 or 6 membered cyclic group. Compounds of the formula (I) or (la) in which some or all of the above-mentioned groups have the preferred or more preferred meanings are also an object of the present invention. Preferred embodiments of the compounds according to present invention are shown in formula (Ha) to (Hi). Furthermore, the present invention provides prodrug compounds of the compounds of the invention as described above. "Prodrug compound" means a derivative that is converted into a compound according to the present invention by a reaction with an enzyme, gastric acid or the like under a physiological condition in the living body, e.g. by oxidation, reduction, hydrolysis or the like, each of which is carried out enzymatically. Examples of the prodrug are compounds, wherein the amino group in a compound of the present invention is acylated, alkylated or phosphorylated to form, e.g., eicosanoylamino, alanylammo, pivaloyloxymethylamino or wherein the hydroxyl group is acylated, alkylated, phosphorylated or converted into the borate, e.g. acetybxy, palmitoyloxy, pivaloybxy, succinytoxy, fumaryloxy, alanyloxy or wherein the carboxyl group is esterified or amidated. These compounds can be produced from compounds of the present invention according to well-known methods. Metabolites of compounds of formula (I) or (la) are also within the scope of the present invention. Where tautomerism, like e.g. keto-enol tautomerism, of compounds of general formula (I) or (la) or their prodrugs may occur, the individual forms, like e.g. the keto and enol form, are claimed separately and together as mixtures in any ratio. Same applies for stereoisomers, like e.g. enantiomers, cis/trans isomers, conformers and the like. If desired, isomers can be separated by methods well known in the art, e.g. by liquid chromatography. Same applies for enantfomers by using e.g. chiral stationary phases. Additionally, enantiomers may be isolated by converting them into diastereomers, i.e. coupling with an enantiomerically pure auxiliary compound, subsequent separation of the resulting diastereomers and cleavage of the auxiliary residue. Alternatively, any enantiomer of a compound of formula (I) or (la) may be obtained from stereoselective synthesis using optically pure starting materials. In case the compounds according to formula (I) or (la) contain one or more acidic or basic groups, the invention also comprises their corresponding pharmaceutically or toxicologically acceptable salts, in particular their pharmaceutically utilizable salts. Thus, the compounds of the formula (I) or (la) which contain acidic groups can be present on these groups and can be used according to the invention, for example, as alkali metal salts, alkaline earth metal salts or as ammonium salts. More precise examples of such salts include sodium salts, potassium salts, calcium salts, magnesium salts or salts with ammonia or organic amines such as, for example, ethylamine, ethanolamine, triethanolamine or amino acids. Compounds of the formula (I) or (la) which contain one or more basic groups, i.e. groups which can be protonated, can be present and can be used according to the invention in the form of their addition salts with inorganic or organic acids. Examples for suitable acids include hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, nitric add, methanesulfonic add, p-toluenesutfonic add, naphthalenedisulfonic adds, oxalic add, acetic add, tartaric add, lactic acid, salicylic add, benzoic acid, formic add, propionic add, pivalic add, diethylacetic add, malonic add, sucdnic add, pimelic add, fumaric add, maleic add, malic add, sulfaminic add, phenylpropionic add, gluconic add, ascorbic add, tsonicotinic add, titric acid, adipic acid, and other adds known to the person skilled in the art If the compounds of the formula (I) or (la) simultaneously contain addic and basic groups in the molecule, the invention also indudes, in addition to the salt forms mentioned, inner salts or betaines (zwitterions). The respective salts according to the formula (I) or (la) can be obtained by customary methods which are known to the person skilled in the art like, for example by contacting these with an organic or inorganic acid or base in a solvent or dispersant, or by anion exchange or cation exchange with other salts. The present invention also includes all salts of the compounds of the formula (I) or (la) which, owing to low physiological compatibility, are not directly suitable for use in Pharmaceuticals but which can be used, for example, as intermediates for chemical reactions or for the preparation of pharmaceutically acceptable salts. The present invention provides compounds of general formula (I) or (la) or their prodrugs as DPP-IV inhibitors. DPP-IV is a cell surface protein that has been implicated in a wide range of biological functions. It has a broad tissue distribution (intestine, kidney, liver, pancreas, placenta, thymus, spleen, epithelial cells, vascular endothelium, lymphoid and myeloid cells, serum), and distinct tissue and cell-type expression levels. DPP-IV is identical to the T cell activation marker CD26, and it can deave a number of immunoregulatory, endocrine, and neurological peptides in vitro. This has suggested a potential role for this peptidase in a variety of disease processes. DPP-IV related diseases are described in more detail in WO-A-03/181 under the paragraph "Utilities" which is herewith incorporated by reference. Accordingly, the present invention provides compounds of formula (I) or (la) or their prodrugs or pharmaceutically acceptable salt thereof for use as a medicament. Furthermore, the present invention provides the use of compounds of formula (I) or (la) or their prodrugs or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment or prophylaxis of norHnsulin dependent (Type II) diabetes mellitus; hyperglycemia; obesity; insulin resistance; iipid disorders; dyslipidemia; hyperiipidemia; hypertriglycerkiemia; hypercholestrerolemia; low HDL; high LDL; atherosclerosis; growth hormone deficiency; diseases related to the immune response; HIV infection; neutropenia; neuronal disorders; anxiety; depression; tumor metastasis; benign prostatic hypertrophy; gingivitis; hypertension; osteoporosis; diseases related to sperm motility; low glucose tolerance; insulin resistance; ist sequelae; vascular restenosis; irritable bowel syndrome; inflammatory bowel disease; including Crohn's disease and ulcerative colitis; other inflammatory conditions; pancreatitis; abdominal obesity; neurodegenerative disease; retinopathy; nephropathy; neuropathy; Syndrome X; ovarian hyperandrogenism (polycystic ovarian syndrome; Type n diabetes; or growth hormone deficiency. Preferred is non-insulin dependent (Type II) diabetes mellitus and obesity. The present invention provides pharmaceutical compositions comprising a compound of formula (I) or (la), or a prodrug compound thereof, or a pharmaceutically acceptable salt thereof as active ingredient together with a pharmaceutically acceptable carrier. "Pharmaceutical composition" means one or more active ingredients, and one or more inert ingredients that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, the pharmaceutical compositions of the present invention encompass any composition made by admixing a compound of the present invention and a pharmaceutically acceptable carrier. A pharmaceutical composition of the present invention may additionally comprise one or more other compounds as active ingredients like one or more additional compounds of formula (I) or (la), or a prodrug compound or other DPP-IV inhibitors. Other active ingredients are disclosed in WOA-03/181 under the paragraph "Combination Therapy" which is herewith incorporated by reference. Accordingly, other active ingredients may be insulin sensitizers; PPAR agonists; biguanides; protein tyrosinephosphatase-IB (PTP-1B) inhibitors; insulin and insulin mimetics; suffonylureas and other insulin secretagogues; a-glucosidase inhibitors; glucagon receptor antagonists; GLP-1, GLP-1 mimetics, and GLP-1 receptor agonists; GIP, GIP mimetics, and GIP receptor agonists; PACAP, PACAP mimetics, and PACAP receptor 3 agonists; cholesterol lowering agents; HMG-CoA reductase inhibitors; sequestrants; nicotinyl alcohol; nicotinic acid or a salt thereof; PPARa agonists; PPARoly dual agonists; inhibitors of cholesterol absorption; acyl CoA : cholesterol acyltransferase inhibitors; anti-oxidants; PPARo agonists; antiobesity compounds; an ileal bile add transporter inhtortor; or anti-inflammatory agents or pharmaceutically acceptable salts of these active compounds. The term "pharmaceuticaUy acceptable salts'9 refers to salts prepared from pharmaceutically acceptable norvtoxjc bases or adds, including inorganic bases or acids and organic bases or acids. The compositions include compositions suitable for oral, rectal, topical, parenteral (including subcutaneous, intramuscular, and intravenous), ocular (ophthalmic), pulmonary (nasal or buccal inhalation), or nasal administration, although the most suitable route in any given case will depend on the nature and severity of the conditions being treated and on the nature of the active ingredient. They may be conveniently presented in unit dosage form and prepared by any of the methods well-known in the art of pharmacy. In practical use, the compounds of formula (I) or (la) can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral or parenteral (including intravenous). In preparing the compositions for oral dosage form, any of the usual pharmaceutical media may be employed, such as, for example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like in the case of oral liquid preparations, such as, for example, suspensions, elixirs and solutions; or carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents and the like in the case of oral solid preparations such as, for example, powders, hard and soft capsules and tablets, with the solid oral preparations being preferred over the liquid preparations. Because of their ease of administration, tablets and capsules represent the most advantageous oral dosage unit form in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be coated by standard aqueous or nonaqueous techniques. Such compositions and preparations should contain at least 0.1 percent of active compound. The percentage of active compound in these compositions may, of course, be varied and may conveniently be between about 2 percent to about 60 percent of the weight of the unit The amount of active compound in such therapeutically useful compositions is such that an effective dosage will be obtained. The active compounds can also be administered irrtranasaUy as, for example, liquid drops or spray. The tablets, pills, capsules, and the fike may also contain a binder such as gum tragacanth, acacia, com starch or gelatin; exctpients such as dicaltiurn phosphate; a disintegrating agent such as corn starch, potato starch, aiginic ack); a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, lactose or saccharin. When a dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier such as a fatty oil. Various other materials may be present as coatings or to modify the physical form of the dosage unit. For instance, tablets may be coated with shellac, sugar or both. A syrup or elixir may contain, in addition to the active ingredient, sucrose as a sweetening agent methyl and propylparabens as preservatives, a dye and a flavoring such as cherry or orange flavor. Compounds of formula (I) or (la) may also be administered parenterally. Solutions or suspensions of these active compounds can be prepared in water suitably mixed with a surfactant such as hydroxy-propylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols and mixtures thereof in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils. Any suitable route of administration may be employed for providing a mammal, especially a human, with an effective dose of a compound of the present invention. For example, oral, rectal, topical, parenteral, ocular, pulmonary, nasal, and the like may be employed. Dosage forms include tablets, troches, dispersions, suspensions, solutions, capsules, creams, ointments, aerosols, and the like. Preferably compounds of formula (I) or (la) are administered orally. The effective dosage of active ingredient employed may vary depending on the particular compound employed, the mode of administration, the condition being treated and the severity of the condition being treated. Such dosage may be ascertained readily by a person skilled in the art When treating or preventing diabetes mellitus and/or hyperglycemia or hypertriglyceridemia or other diseases for which compounds of Formula I are indicated, generally satisfactory results are obtained when the compounds of the present invention are administered at a daily dosage of from about 0,1 milligram to about 100 milligram per kilogram of animal body weight, preferably given as a single daily dose or in divided doses two to six times a day, or in sustained release form. For most large mammals, the total daily dosage is from about 1.0 milligrams to about 1000 milligrams, preferably from about 1 milligrams to about 50 milligrams. In the case of a 70 kg adult human, the total daily dose will generally be from about 7 milligrams to about 350 milligrams. This dosage regimen may be adjusted to provide the optimal therapeutic response. The compounds of formula (I) of the present invention can be prepared from beta amino acid intermediates such as those of formula (IV) and substituted amine intermediates such as those of formula (III), using standard peptide coupling conditions. The preparation of these intermediates is described in the following schemes. Some abbreviations that may appear in this application are as follows. ABBREVIATIONS Designation bs Broad singlet bm Broad multiplet Boc (or BOC) terf-Butoxycarbonyl CDI A/,A/-Cartx>nyldiimidazole DCE 1,2-Dichbroethane DCM Dtchloromethane DIEA Diisopropytethyiamine DMF W,W-Dirnethytformamkte EDC 1^thyl-3-{3-dimethylamino^^ hydrochloride EtaN Triethylamine Fmoc 9-Fluorenylmethoxycart)onyl HATU 0^-Azabenzo4riazoM-yl)-AW hexafluorophosphate HCI Hydrogen chloride HOBt 1 -Hydroxybenzotriazole HPLC High pressure liquid chromatography M.P. Melting point NMR Nuclear Magnetic Resonance PG Protecting group rt Retention time *BuOH terf-Butanol TFA Trifluoroacetic add TLC Thin Layer Chromatography Available starting materials may be amines having the formula (III). They may be purchased from commercially available sources such as Acros, Astatech, Array, Sigma-Aldrich, Fluka, ABCR or be synthesized by one skilled in the art Common reactions between compounds containing amino groups and carboxyl, sutfonyl or isocyanate functionalities may be employed for their synthesis with suitable functionalized starting materials. Nudeophilic substitution reactions between compounds containing a suitable leaving group (e.g., halogenide, mesylate, tosylate) and nucleophiles (e.g., amines) may be also employed. The conversion of diverse functional groups (such as esters, alcohols, amides, nitrites, azides) may allow the synthesis of some intermediates or final compounds. Schemes A through G outline general procedures for the synthesis of some compounds described below. Unless otherwise indicated in the schemes, the variables have the same meaning as described above. may be commercially available, known in the literature or may be conveniently synthesized using one of the methods already published and reviewed in e.g., Cole, Tetrahedron, 32, 9517 (1994), Juaristi et al., Aldrichimica Ada, 27, 3, 1994, or Juaristi, Enantioselective Synthesis ofp-Amino Adds, Ed. Wiley-VCH, New York, 1997. In particular, 3-amino-4-(2,4,5-trifluoro-phenyl)-butyric acid may be synthesized by a variety of methods as reported in the patent applications WO 2004069162, WO 2004064778, WO 2004037169, WO 2004032836 and in the articles JACS, 126, 3048 (2004) and JACS, 126, 9918 (2004). Unless otherwise noted, all non-aqueous reactions were carried out under argon atmosphere with commercial dry solvents. Compounds were purified using flash column chromatography using Merck silica gel 60 (230-400 mesh) or reverse phase preparative HPLC using a Reprosil-Pur ODS3, 5 pm, 20 x 125 mm column with Shimadzu LC8A-Pump and SPD-10Avp UV/Vis diode array detector. The 1H-NMR spectra were recorded on a Varian VXR-S (300 MHz for 1H-NMR) using de-dimethylsutfoxide as solvent; chemical shifts are reported in ppm relative to tetramethytsilane. Analytical LC/MS was performed using Reprosil-Pur ODS3, 5 pMt 1 x 60 mm columns with a linear gradient from 5% to 95% acetonitrile in water (0.1% TFA) at a flow rate of 250 pl/min; retention times are given in minutes. Methods are: (I) runs on a LC10Advp-Pump (Shimadzu) with SPD-M10Avp UV/Vis diode array detector and QP2010 MS-detector in ESN- modus with UV-detection at 214, 254 and 275 nm, 10 min. linear gradient; (II) Kterci but 5 min. Hnear gradient; (III) runs on a LC10Advp-Pump (Shimadzu) with SPCMGAvp dual wavelength UV-detector and QP2010 MS-detector in ESI+ modus with UV-detection at 214 and 254 nm, 10 min. linear gradient; (IV) idem but 5 min. linear gradient; (V) runs on a LC10Advp-Pump (Shimadzu) with SPD-M10Avp UV/Vis diode array detector and QP2010 MS-detector in ESI+ mode with UV-detection at 214, 254 and 275 nm, with a linear gradient different from 5% to 95% acetonitrile in water (0.1% TFA or formic acid). In this case the data will be reported as follows: LC/MS (V) (5-90%, 5 min): rt 1.60, m/z 171 (M+H)+ ; (VI) runs on a LC10Advp-Pump (Shimadzu) with SPEMOAvp dual wavelength UV-detector and QP2010 MS-detector in ESI+ modus with UV-detection at 214 and 254 nm, with a linear gradient different from 5% to 95% acetonitrile in water (0.1% TFA or formic acid). In this case the data will be reported as follows: LC/MS (VI) (5-90%, 5 min): rt 1.60, m/z 171 (M+H) +; method (VII) is run on a LiChroCART 30-4 Purospher STAR RP-18, endcapped, 3 urn (Merck) column. Gradient elution using eluent (A): acetonitrileAvater (5:95) with a 20 mM HCO2NH4/NH4OH buffer at pH 7.4. Eluent (B): acetonitrile/water (80:20) with a 20 mM HCO2NH4/NH4OH buffer at pH 7.4. Gradient 0 minutes 70:30 (%A:%B); 2.5 minutes 5:95 (%A:%B); 4.3 minutes 5:95 (%A:%B); 4.4 minutes 70:30 (%A:%B); 5 minutes 70:30 (%A:%B). Row rate 1.5 mL/minute; UV-detection 220 nM. General procedure for making compounds of the invention In general, compounds having the formula (I) wherein the variables have the above described meanings, may be prepared using standard peptide coupling conditions, reagents and protective groups. For example, it may be possible to use 1-ethyl-3-(3 (EDC) in combination with 1-hydroxybenzotriazole (HOBt) and a base (triethylamine or diisopropylethylamine) or O^-azabenzotriazoH-ylJ-N, N, N\ N-tetramethyluronium hexafluorophosphate (HATU) in the presence of a base, in solvents such as methylene chloride or W,A/-dimethylformamide. Scheme H outlines a procedure for using the amines formed according to Schemes A through G to synthesize compounds that are embodiments of the invention. The protective group may be removed with, for example, diethylamine in dichloromethane in the case of 9-ftuoreny»methoxycarbony! or using acidic conditions (such as trifluoroacetic acid in dichloromethane or hydrochloric acid in dioxane) in the case of tert-butoxycarbonyt, as described in Protective Groups in Organic Synthesis 3rd ed., Ed. Wiley-VCH, New York; 1999. For the purification of intermediates or end products, flash chromatography on sil jca gel may be suitable for the free amines whereas the use of preparative HPLC leads to the isolation of the corresponding trifluoroacetic acid or formate salts. EXAMPLES The following examples are provided so that the invention might be more fully understood. These examples are illustrative only and should not be construed as limiting the invention in any way. {2SHBercmvtaminc>-methvDH^ acid fe/f-butvl ester. A mixture of 127 mg (1.04 mmoQ of benzoic acid, 219 mg (1.14 mmol) of 1-ethyt-3-(3-dimethylaminopropyl)carbodHmide hydrochloride (EDC), 154 rng (1.14 mmol) of 1-hydroxybenzotriazole (HOBt) and 271 \A (1.56 mmol) of diisopropytethylamine (DIEA) in 2 mL of W.W-dimethytformamide is stirred at room temperature for 10 minutes, before a solution of 250 mg (1.24 mmol) of (2S)-2-aminomethyl-pyiTOlidine-1-carboxylic acid te/t-butyl ester in 2 mL of W,/V-dimethylforrnamide is added and stirring continued overnight The solution is diluted with 50 mL of ethyl acetate, washed sequentially with 5% citric acid aqueous solution, saturated aqueous sodium bicarbonate solution, and brine, dried over sodium sulphate and the solvent is removed under reduced pressure. Purification of the crude product by flash chromatography (silica gel, eluent: 0% to 10 % of ethyl acetate in cyclohexane) gives the title compound. 1H-NMR 8(ppm) = 1.40 (s, 9H), 175-1.88 (m, 4H), 3.39-3.50 (m, 1H), 3.90-3.98 (m, 1H), 7.41-7.47 (m, 4H), 7.78-7.81 (m, 1H), 8.34-8.39 (m, 1H). LC/MS (IV) rt 2.79, m/z368 (M+Na+CH3CN)+. Af-Pvrrplidin-f2S)-vlmethvl-benzarnide (TFA salt). A solution of 20.0 mg (0.07 mmol) of (2S>(benzoylamino-methyl>-pyrrolidine-1-carboxylic add ferf-butyl ester (step 1) in 1.0 mL of dichloromethane and 0.5 mL of trifluoroacetic acid is stirred at room temperature for 30 minutes and then evaporated under reduced pressure to give the title compound. The intermediates in Table 1 are synthesized according to the procedure shown for Example 1. gS)-Benzvloxvmeth^PwrDtkiine-1-carboxvlic acid fert-butvt ester. (For the synthesis see also J. Med. Chem.\ 42; 4; 1999; 677-690) A solution of 500 mg (2.48 mmol) of {2S>JiydroKymethyl-pyrro^ acid terf-butyt ester in 2 mL of tetrahydrofuran is added dropwise to a slurry of 119.2 mg (60% dispersion in oil, 2.98 mmol) of sodium hydride in 2 mL of tetrahydrofuran at 0 °C and the mixture stirred for 5 minutes. 325 jiL (119 mg, 2.73 mmol) of benzylbromide is added and the reaction is allowed to warm to room temperature and stirred overnight Water and 1N hydrochloric acid solution are added and the mixture is extracted with ethyl acetate. The collected organic phases are washed sequentially with a saturated aqueous sodium bicarbonate solution, brine and water, then dried over sodium sulphate and evaporated under reduced pressure. The crude mixture is purified using flash chromatography (silica gel, eluent: 0% to 10% ethyl acetate in cyclohexane) to afford the title compound. LC/MS (IV) rt 3.41, m/z233 (M+H-Boc+AcCN)*. ^2S)-BenzYloxvmethv^pyrrolidine, (TFA satt). A solution of 300 mg (1.03 mmol) of (2S>-benzyloxymethyl-pyrrolidine-1-cartx)xylic acid teri-butyl ester (step 1) in 1.5 mL of dichloromethane and 1.5 mL of trifiuoroacetic acid is stirred at room temperature for 1 h and then evaporated under reduced pressure. The crude mixture is diluted in 5 mL of dichloromethane and stirred for 1 h with 1.43 g (4.12 mmol) of (polystyrylmethyl)trimethylammoroum bicarbonate, then filtered and evaporated under reduced pressure to give the title compound. 1H-NMR 5 (ppm) = 1.34-1.42 (m, 1H), 1.5&-1.81 (m, 3H), 2.76-2.86 (m, 2H)( 3.27-3.33 (m, 4H), 4.47 (s, 2H), 7.2&72A (m, 5H). LC^MS (III) rt 2.62» mfe 192 (M+H)+. 2-Methoxvmethvt-pyrrDl>din&'1-carboxvHc acid tert-butyl ester A solution of 150 mg (0.75 mmol) erf N-Boc-prolinol and 33 mg (0.82 mmol) of sodium hydride in 1 mL of tetrahydrofuran is stirred for 10 minutes at room temperature. 128 mg (0.90 mmol) of methyliodide in 0.5 mL THF are added and the reaction is stirred 1h. Methanol is added and the solvent is evaporated under reduced pressure. To the crude material 1N hydrochloric acid solution is added and the mixture is extracted with ethyl acetate. The collected organic phases are washed with brine and water, then dried over sodium sulphate and evaporated under reduced pressure. The crude mixture is purified using flash chromatography (silica gel) to afford the title compound. LC/MS (II) rt 4.46t m/z 201 (M+H~CH3) 2-Methoxvmethvt~p\nTolidine. (TFA salt). A solution of 51 mg (0.24 mmol) of the product from step 1 in 1 mL of trifluoroacetic acid and 2 mL of dichbromethane is stirred at room temperature for 1 h and then evaporated under reduced pressure. The product is isolated in the form of a TFA-salL 1H-NMR 5(ppm) = 1.50-1.65 (m, 1H), 1.80-2.10 (m, 3H), 3.0&3.25 (m, 2H), 3.30 (s, 3H), 3.40-3.46 (m, 1H), 3.51-3.56 (m, 1H), 3.60-3.75 (m, 1H), 8.55 (s, 3H), 9.18 (s, 3H). 2-Cvclopropvlmethoxvmethvl-pvrrolidine-i-carboxvlic acid tert-butvl ester To a solution of 100 mg (0.50 mmol) of (2S>hydroxymethyl-pynrolidine-1-carboxyIic acid ferf-butyl ester in 500 yL tetrahydrofuran is added sodium hydride (40 mg, 60% dispersion in oil, 0.99 mmol) and the mixture is stirred for 10 minutes. (Bromomethyl)cyclopropane (202 mg, 1.49 mmol) is added and the reaction is heated in the microwave for 10 minutes at 100 °C. Ethyl acetate is added and the mixture is washed with brine (3x), then dried over sodium sulphate and evaporated under reduced pressure. The crude mixture is purified using flash chromatography (silica gel, eluent 10% ethyl acetate in cyclohexane) to afford the title compound. LC/MS (II) rt 4.55, m/z 256 (M+H-CHa)*. 2-CvcloproDvlmethoxvmethvl-pvrrolidine. (TFA salt) Obtained from the product of step 1 according to the procedure described for steps 2 in Example 1. 2-Phenoxvmethvl-Pvrrolidine-i-carboxvlic acid tort-butyl ester To 1.02 g (1.12 mmol) of polymer bound triphenylphosphine in 5 mL dichloromethane 156 mg (0.89 mmol), diethylazodicarboxylate (DEAD) is added at 0 °C and the mixture is stirred for 5 minutes. To the mixture a solution of 150 mg (0.75 mmol) of Boc-L-prolinol, 70 mg (0.75 mmol) of phenol and 116 pj (1.13 mmol) of triethylamine in 2 mL dichloromethane are added and the reaction is allowed to warm to room temperature and stirred over 60 h. The polymer is filtered off and the solution is evaporated under reduced pressure. The crude mixture is purified using flash chromatography (silica gel, eluent: 0% to 20% ethyl acetate in cydohexane) to afford the title compound. LC/MS (III) rt 5.68, mfe 263 (M+H-CHa)*. 2-Phenoxvmethvl-pvrrolidine (TFA salt) Obtained from the product of step 1 according to the procedure described for steps 2 in Example 1. 1H-NMR 6 (ppm) = 1.65-1.80 (mt 1H), 1.86-2.03 (m, 2H), 2.07-2.18 (m, 1H), 3.05-3.15 (m, 2H), 3.90 (bs, 1H), 4.07 (dd, 1H), 4.23 (dd, 1H), 6.93-6.97 (m, 3H), 7.26-7.32 (m, 2H), 8.72 (bs, 1NH), 9.27 (bs, 1NH). LC/MS (III) rt 2.77, mfe 178 (M+H)+. /2SHBenzenesutfonvtamrrKHn^^ acid terMxitvl ester. To a solution of 150 mg (0.75 mmoO of f2S>amirKxriethyl-pyrror>dine-1-carboxy)ic acid terf-butyl ester and 117 jiL (90.0 mg, 0.90 mmol) of triethylamlne in 3 roL of dichloromethane is added 62 jxL (85.7 mg, 0.80 mmol) of benzenesutfonytchloride at 0 °C. The mixture is stirred for 15 h at room temperature and then evaporated under reduced pressure to give a crude mixture containing approx. 70% of the title compound, which is taken directly to the next step. LC/MS (I) rt 4.34, m/z241 (M~+H-Boc)+. Step 2 A/-PvrroiidirvgS^lrnethvl-benzensuHbnamide (TFA saltt. A solution of 231 mg (appro* 70% purity, 0.47 mmol) of (2SHbenzenesulfonylamino- methyl>-pynrolidine-1-carboxylic arid ferf-butyl ester (Step 1) in 1.5 mL of dichloromethane and 0.5 mL of trifluoroacetic add is stirred at room temperature for 2 h and then evaporated under reduced pressure. The oily product is diluted in 5 mL of dichloromethane and filtered through aluminium oxide (eluent 0% to 10% methanol in dichloromethane). The collected fractions are concentrated to give the title compound. 1H-NMR 5 (ppm) =1.53-1.65 (m, 1H), 1.81-2.05 (m, 3H), 2.91-3.16 (m, 5H), 3.50-3.55 (m, 1H), 7.27-7.29 (m, 1H), 7.58-7.60 (m, 2H), 7.78-7.80 (mf 2H), 7.99 (t, ^=7.6 Hz, 1H),9.15(bs,1H). LC/MS (I) rt2.11, m/z241 (M+H)+. The compounds in Table 3 are synthesized according to the procedure shown for Example 20. 24(Cvclopropanesulfonvl-methvi"aminoVmethvn-pvrrolicline-1 -carboxvlic acid tert-butvl ester To a solution of 45 mg (0.15 mmol) of 2-(cyclopropanesuIfonylamino-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (step 1, example 18) in 1 mL of tetrahydrofuran, 7.1 mg (0.30 mmoi) of sodium hydride in 0.5 mL THF is added and the reaction is stirred 5 minutes. 14 yd (0.22 mmol) of methyliodide are added slowly and reaction is stirred overnight The solvent is evaporated under reduced pressure, the crude material is dissolved in ethyl acetate and washed sequentially with 5% aqueous citric acid solution and saturated aqueous sodium bicarbonate solution, and brine, dried over sodium sulphate and the solvent is removed under vacuum. The crude material is used without further purification in the next step. LC/MS (V) (5-90%t 5 min): rt 2.85, m/z 382 (M+H+Na+AcCN)+. Cvdopropanesulfonic acid methvkpvrrDlidin-2-vlmethvl-amide (TFA salt). Obtained from the product of step 1 according to the procedure described for steps 2 in Example 1. LC/MS (V) (5-90%t 5 min): rt 022, mfe 241 (W*H+Na)*. (2S)-{(3-phenyl-uureido)-methyl]-pyrrolidine-1-carboxylic acid terf-butyl ester. A solution of 150 mg (0.75 mmol) of (2S)-aminomethyl-pynroiiciine-1-carboxylic acid tert-butyl ester and 86 \± (93.7 mg, 0.79 mmol) of phenyl isocyanate in 3 mL of dioxan is stirred at 90 °C for 5 h. After evaporation of the solvent under reduced pressure, the crude mixture (approx. 50% content of title product) is used in the next step without further purification. LC/MS (III) rt 4.18, m/z 320 (M+H)+. 1-Phenvl-3-Pvrrolidin-/2S)-vlmethvl-urea (TFA salt). A solution of 253 mg (approx. 0.37 mmol) of (2S>[(3-ph«nylHjreido>-methyl}-pyrrolidtne-1-carboxylic actd tert-butyf ester (step 1) in 0.5 mL of trifluoroacetic acid and 1.0 mL of dichloromethane is stirred at room temperature for 2 h and then evaporated under reduced pressure. The crude mixture is dissolved in 2 mL of a 1M ammonia solution in methanol, concentrated under reduced pressure and then purified using flash chromatography (aluminium oxide, eluent 0% to 10% methanol in dichloromethane containing 0.1% of ammonia) to give the title compound. 1H-NMR S (ppm) = 1.35-1.40 (m, 1H), 178-1.81 (m, 5H), 2.85-2.84 (m, 2H), 3.02-3.22 (2H), 4.35 (bs, 2H), 6.38 (bs, 1H), 6.83 (t, J=10.0 Hz, 1H)t 7.16 (t, J=10.0 Hz, 2H), 7.35 (d, J=10.0 Hz, 2H), 8.65 (bs, 0.1H), 8.77 (bs, 0.9H). LC/MS (I) rt 1.88, m/z 220 (M+H)+. Boo-azettdine-3-carboxvlic acid To a solution of 100 mg (0.99 mmol) 3-azetidine carboxylic add in 15 mL THF is added 5 mL of saturated sodium bicarbonate solution and 238 mg (1.09 mmol) di-terf- butyl dicarbonate. The mixture is stirred overnight at room temperature, acidified with 5% aqueous hydrochloric acid and extracted three times with ethyl acetate. The combined organic layers are washed with brine and dried over sodium sulphate. Removal of the solvent in vacuum yields the product that was used without further purification for the next step. LC/MS (II) rt 2.08, mfe 187 (M+H-CH3)*. 3-Hvdroxvmethvl-azetidine-1-carboxvBc acid tert-butvl ester A mixture of 212 mg (0.99 mmol) of the crude material from step 1 and 241 mg (1.49 mmol) CDI in 15 mL dry tetrahydrofurane \s stirred for 2 h at room temperature, then cooled to 0°C and a suspension of 56 mg (1.49 mmol) sodium borohydride in water added quickly. After another 1 h at 0°C acetone is added, the mixture allowed to warm to room temperature and the solvent removed. The remaining material is dissolved in ethyl acetate and water, the layers separated and the organic layer washed with 5 % citric acid, saturated sodium bicarbonate solution and brine. Drying over sodium sulphate and removal of the solvent affords the alcohol. LC/MS (II) rt 1.81, m/z 173 (M+H-CH3)+. 3-Phenoxvmethvl-azetidine-i-carboxvlic acid tort-butyl ester To a solution of 94 mg (0.5 mmol) Boc protected hydroxymethyl azetidine (step 2) in 5 mL of THF was added 354 mg (0.5 mmol) fluorous triphenyl phosphine and 47 mg (0.5 mmol) phenol. The mixture was cooled down to 0 °C and 405 mg (0.5 mmol) fluorous diethyl azodicarboxylate (DEAD) was added and allowed for warm up to room temperature. The reaction was stirred for 3 days, evaporated to dryness over 1 g of alumina. Alumina containing the reaction product was placed over fluorous silica cartridge and washed with methanol:water 4:1 eluent (4x1 mL). The filtrate was concentrated under reduced pressure and subjected to preparative TLC (silica, hexanes: ethyl acetate 1:1) to afford the title product LC/MS 01) rt 1.89, m/z 164 (M+H-Boc) 3-Phenoxvmethvl-azetidine fTFA salt) A solution of 34.0 mg (0.13 mmol) of 3-phenoxymethyl-azetidine-1-carboxylic acid tert-butyl ester (step 3) in 300 jiL of trifluoroacetic acid and 300 pi of dichloromethane is stirred at room temperature for 30 minutes and then evaporated under reduced pressure to give the title compound. Example 29 2-(Azetidirv3-vtmethoxvy-Pvridine (TFA salt). Obtained from 3-hydroxymethyI-azetidine-1-carboxylic add tert-butyl ester and pyridirv 2-ol according to the procedure described for steps 3 and 4 in Example 28. LC/MS (II) rt 0.25, m/z 165 (M+H)+. S-Methanesulfonvloxvmethvl-azetidine-i-carboxvlicacid tert-butvl ester To 170 mg (0.90 mmol) of 3-hydroxymethyl-azetidine-1-carboxylic acid tert-butyl ester in 10 mL dry dichloromethane 155 pi (1.08 mmol) triethylamine and 75 \J\ (0.99 mmol) methanesulfonic acid chloride are added at 0°C. After 4 h at 0°C dichloromethane (50 mL) is added and the organic layer washed twice with brine. The organic layer is dried over sodium sulphate and the solvent removed, yielding crude material that is directly taken to the next step. LC/MS (II) rt 2.35, m/z 251 (M+H-CH3)+. 3-Azidornethvlazetidine-1-carboxvlic acid tert-butvl ester A mixture of 3-methanesulf6nyloxymethyl-azetidHTe-1-carboxylic acid tert-butyl ester (266 mg, 0.90 mmol, step 1) and 176 mg (2.70 mmol) sodium azide in 10 mL dry N,N- dimethytformamide is heated to 90 °C for 1 h. For workup 60 mL of ethyl acetate are added and the organic layer is washed thoroughly with brine (3x), dried over sodium sulphate and concentrated under reduced pressure. Purification by flash chromatography on silica gel (cydohexane to 20% ethylacetate in cydohexane) yields the azide. LC/MS (II) rt 2.57, mfe 198 (N^H-CHaf. 3-Aminomethvl-azetidine-1-carboxvlic acid tert-butvl ester 73 mg (0.35 mmol) of 3-azidomethyl-azetidine-1-carboxylic acid tert-butyl ester (step 2) dissolved in 20 mL methanol, 1 mL ammonia (2M in MeOH) and Pd/C (5% with 50% water) added and the mixture stirred at 1 atm H2 for 1 h. Filtration over Celite and evaporation of the solvent affords the crude amine that is taken directly to the next step. LC/MS (IV) rt 1.75, m/z 172 (M+H- CH3)+. 3-(Benzenesufonvlamine-methvlVazetidine-1--carboxvlic acid tert-butvt ester 39 mg (0.21 mmol) of 3-aminomethyl-azetidine-1-carboxylic acid tert-butyl ester (step 3) and 32pl (0.25 mmol) triethylamine are dissolved in dichloromethane and 17 \s\ (0.23 mmol) of benzenesulfonylchloride added at 0°C. The reaction mixture is subsequently stirred for 1h and diluted with dichloromethane. The organic layer is washed with 5% citric acid, saturated sodium bicarbonate solution and brine and dried over sodium sulphate. The crude product is purified by flash chromatography on silica gel (cyclohexane to 20% ethyl acetate \n cyclohexane). LC/MS (IV) rt 2.64, m/z 312 (M+H-CHs)*. A/-Azetidin-3-vlmethvl-ben2enesulfbnamicle (TFA salt). Obtained from the product of step 4 according to the procedure described for step 2 in example 1. LC/MS (IV) rt 1.73, m/z 227 (M+H) A^Rperidirv3-yimethyH3enzenesutfonamide fTFA salt). Obtained from 1-Boc-piperidine-3-carboxylic acid according to the procedure described for example 30. * LC/MS(IV)rt1.87,m/z255(M+H)+. {f3RH/2S)-Benzvioxvmethvlpvn^ acid te/t-butvl ester. A mixture of 44.8 mg (0.15 mmol) of f3R>ferf-butoxycarbonylamino-4-[2-fluoro-phenyO-butyric acid, 28.3 mg (0.21 mmol) of 1-hydroxybenzotriazole (HOBt), 39.9 mg (0.21 mmol) of 1-ethyl-3-(3«dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 100 pL (98.2 mg, 0.76 mmol) of diisopropylethylamine in 2.5 mL of A/,A/-dimethylformamide is stirred for 5 minutes. After addition of 50.0 mg (0.17 mmol) of (2S)-benzyloxymethylpyrrolidine (Example 10) in 0.5 mL of A/,A/-dimethylformamide, the mixture is stirred for further 16 h. The solution is diluted with 5 mL of 1N hydrochloric acid solution and extracted twice with 10 mL of dichloromethane. The collected organic phases are washed with brine and water, dried over sodium sulphate and evaporated under reduced pressure. The residue is purified using flash chromatography (silica gel, eluent 0% to 10% methanol in dichloromethane) to afford the title compound. LC/MS (I) rt 5.68, m/z 471 (M+H)+. ffi?)-Amino-14f2S)-benzvtoxymethvh^^ (TFA salt). A solution of 8.00 mg (0.017 mmol) of {p/?H(2S>tenzyloxyrnethy^ (24luoro4>enzyO-3^xo-propy^J-carbamlc acid fe/f-butyl ester (Step 1) in 0.5 mL of trifluoroacetjc acid and 1 mL of dichloromethane is stirred at room temperature for 1 h and then evaporated under reduced pressure. The crude mixture is purified using HPLC (eluent 5% to 95% acetonitrile in water with 0.1% of trifluoroacetic acid) to afford the title compound. 1H-NMR 5 (ppm) = 1.79-1.87 (m, 3H), 2.85-2.92 (m, 1H), 2.98-3.05 (m, 1H), 3.21-3.32 (m, 5H), 3.43-3.47 (m, 1H), 3.69 (bs), 3.93-3.95 (m, 0.3H), 4.05-4.10 (mt 0.7H). 4.41-4.45 (m, 3H)( 7.11-7.18 (m, 2H), 7.21-7.32 (m, 7H), 7.94 (bs, 2H). LC/MS (!) rt 3.60, m/z 371 (M+H)*. The compounds in Table 4 are synthesized according to the procedure shown for example 32. Using a procedure similar to those outlined for example 32, the following compounds were prepared. fl3RHgSHBenzovlaminoHfnethvl>^ carbamic acid terf-butvl ester. Obtained from (3R>te/*butoxycarbonylamino^ acid and N- pyrrolidin-f2Sj-ylmethyl-benzamide (Example 1) according to the procedure described for step 1 in example 32. LC/MS (II) rt 2.99, m/z 506 (M+Na) ff3RHylamincMnefo^ carbamic acid tert-butvl ester (TFA salty Obtained from the product of step 1 according to the procedure described for step 2 in example 32. 1H-NMR 5 (ppm) = 1.75-1.95 (m, 5H), 2.7&3.20 (m, 3H), 3.32-3.37 (m, 2H), 3.69-3.80 (m, 0.5H), 3.90-3.97 (m( 0.2H), 4.18-4.20 (m, 0.4H), 7.12-7.19 (m, 2H)t 7.28-7.33 (m, 5H), 7.37-7.52 (m? 2H), 7.73-7.76 (m, 3H), 7.92 (bs, 2H)t 8.3S«.66 (m, 0.7H), 8.62- 8.66 (m, 0.3H). LC/WIS (H) rt 2.02t m/z 384 (M+H)+. The compounds in Table 5 are synthesized according to the procedure shown for Example 43. n-(3-Chloro-benzvlV3-f2-r(2-meth^ oxo-propyQ-carbamic acid tert-butvl ester A mixture of 23 mg (0.08 mmol) of C3R;-terf-butoxycarbonylamino-4-[3-chloro-phenyl]-butyric acid, 34.2 mg (0.09 mmol) O-(7-Azabenzotriazol-1-yl)-A/,A/,A/;A/'- tetramethyluronium hexafluorophosphate (HATU), and 39.3 \*L (0.22 mmol) of diisopropytethylamine in 2.5 mL of A/,/^methylformamide is stirred for 10 minutes at room temperature. 25.4 mg (0.09 mmol) of 2-methanesulfonyl-A^pynroIidin-2-yImethyl-benzamide (example 2) and 19.6 ^iL (0.11 mmol) of diisopropylethylamine in 1 mL of /V,A/-dimethyfformamide is added to the solution and the mixture is stirred overnight. The solvent is evaporated under reduced pressure. The crude material is dissolved in ethyl acetate and washed sequentially with 5% citric acid aqueous solution and saturated aqueous sodium bicarbonate solution, dried over sodium sulphate and the solvent is removed under reduced pressure. The crude product is used in the next step without further purification. AM143-AmirK>^re-chlOFTH3herwl^ benzamide Obtained from the product of step 1 according to the procedure described for steps 2 in Example 32. LC/MS (8 min 10-70%) rt 3.13, m/z478 (M+H)The compounds in Table 6 are synthesized according to the procedure shown for Example 51. 24(2.2,2-TrWuoro-acetvlaminoVmethvn-Pvrrolidine-1-^^rboxvlic acid tert-butvl ester 2-AminomethyH3yrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 1.00 mmol) is dissolved in 1 ml_ methanol. Triethylamine (113 pi, 1.10 mmol) and trifluoroacetic acid anhydride (210 mg, 0.99 mmol) are added sequentially and the reaction is stirred at room temperature overnight. The solvent is evaporated under reduced pressure and the crude material is purified by flash chromatography (silica gel, eluent 0% to 30% ethyl acetate in cyclohexane) to afford the title compound. LC/MS (IV) rt 2.81, m/z 282 (M+H-CH3)+. 2.2,2"Trrfluoro-N-Pvrrolidin-2-vlmethvl-acetamide (TFA salt). Obtained from the product of step 1 according to the procedure described for step 2 in example 1. 1H-NMR 5 (ppm) = 1.62-1.68 (m, 1H), 1.82-2.10 (m, 3H), 3.13-3.35 (m, 2H), 3.43-3.65 (m, 3H), 8.50 (bs, 1NH), 9.11 (bs, 1NH), 9.60 (bs, 1H). LC/MS (IV) rt 1.15, m/z 197 (M+H)+. M-(2-Huoro4)enzYiy3^xo-342-r^ propvlVcarbamic acid tert-butvl ester Obtained from the product of step 3 and 3-ferf-butoxycarbonylamino-4~(2-fluoro- phenyl)-butyric acid according to the procedure described for step 1 in example 32. LC/MS (IV) rt 3.05, m/z 498 (M+Na)+. f3-(2-AmirK>methvl-Pvnrolidirv1-vlV142-fluoro4)enzvl^ acid tert- butvl ester (1-(2-Fluoro-benzyl)-3-oxo-3^-[(2,2^ propyl)-carbamic acid tert-butyl ester (Step 3,155 mg, 0.33 mmol) is dissolved in 1 mL methanol and 2 mL of a 0.4 N barium hydroxide solution are added. The reaction is stirred overnight at room temperature. The solvent is evaporated under reduced pressure, water is added and the crude material is extracted with dichloromethane. The solvent is evaporated and the crude material is redissolved in a mixture methanol/dichloromethane, dried over sodium sulphate and the solvent is evaporated under reduced pressure. The crude material is used in the next step without further purification. 1H-NMR 5 (ppm) = 1.28 (m, 9H), 1.70-1.95 (m, 4H), 2.32-2.50 (m, 2H), 2.60-2.90 (m, 3H), 3.10-3.50 (m, 4H), 4.00-4.15 (m, 1H), 6.63 (bs, 1H), 7.03-7.08 (m, 2H), 7.18-7.22 (m, 2H). LC/MS (IV) rt 2.27, m/z 380 (M+H) (1-f2-nuoro-benzvlV3-{2-rf3^nethoxv-benzovlaminoVrneth^ prppvtVcarbamic acid tort-butyl ester Obtained from the product of step 4 and 3-methoxy-benzoyl chloride according to the procedure described for steps 1 in Example 32. LC/MS (II) rt 2.97, mte 536 (M+H+Na)+. W^H3-Amino^2-fluoro-phenyl)-butyryQ^ benzamide (TFA salt). Obtained from the product of step 5 according to the procedure described for steps 2 in Example 1. LC/MS (II) rt 2.09, m/z 414 (M+H)+. r3^-KCvdopropanecart)onvlamiro^ benzvlVpropyn-carbamic acid tert-butvl ester A mixture of 70.0 mg (0.21 mmol) of (3/?;-terf-butoxycarbonylamino-4-[2-fluoro-phenyl]-butyric acid, 31.3 mg (0.23 mmol) of 1-hydroxybenzotriazole, 45.0 mg (0.23 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 56 ^.L (0.31 mmol) of diisopropylethylamine in 1 mL of dichioromethane is stirred for 30 minutes at 0 °C. After addition of 87.0 mg (0.26 mmol) of cyclopropanecarboxylic acid (pyrrolidin-2-yimethyl)-amide (Example 4) in 1 mL of dichioromethane and another 56 \iL (0.31 mmol) of diisopropylethylamine, the mixture is stirred overnight at room temperature. The solution is diluted with dichioromethane, washed sequentially with 5% citric acid aqueous solution, saturated aqueous sodium bicarbonate solution, and brine, dried over sodium sulphate and the solvent is removed under vacuum. Purification of the crude product by flash chromatography (silica gel, eluent 5% to 10 % of ethyl acetate in cyclohexane) gives the title compound. f3R^AmtfK>-14gS)-benzvloxym rfTFAsatt) A solution of the product from step 1 in 30% trifluoroacettc acid in dichbromethane is stirred at 0 °C for 1 h and then 1 mL methanol is added. The solvent is evaporated under reduced pressure. The crude mixture is dissolved in dichloromethane and the solvent is removed under reduced pressure. This procedure is repeated 3-4 times. The crude material is purified using HPLC (eluent 5% to 95% acetonitrile in water with 0.1% of trifluoroacetic add) to afford the title compound. 1H-NMR 6 (ppm) = 0.60-0.66 (m, 4H), 1.45-1.54 (m, 1H), 1.70-1.90 (m, 4H), 2.75 (m. 1H), 2.81-3.00 (m, 2H), 3.12-3.21 (m, 2H), 3.45-3.49 (m, 3H), 3.68-3.81 (m 1.5H), 3.98 (m, 0.7H), 7.43-7.62 (m, 2H), 8.10 (bs, 0.6H), 8.14 (s, 0.7H), 8.22 (s, 0.2H), 8.38 (bs, 0.4H) LC/MS (10 min, 1-30%) rt 6.81, m/z 384 (M+H)+. The compounds in Table 8 are synthesized according to the procedure shown for example 63. ff3RHteS)-(Benzov)amino-methv^ carbamic acid fert-butvl ester. Obtained from PR>ferf-butoxycarbonylamirK>^ acid and phenyl-pyrrolidin-f2S>ylmethyl-amine according to the procedure described for step 1 in example 32. LC/MS (W) rt 4.16, mfz 455 (M+H)+. #R)-Amino^(2-fluorc>-phenvlH-f f2S)-^ (TFA salt). Obtained from the product of step 1 according to the procedure described for step 2 in example 32. 1H-NMR 5(ppm) = 1.7&-1.90 (m, 6H), 2.77-3.35 (m, 10H), 3.70-3.79 and 4.10-4.15 (2m, 1H), 4.90 (bs), 6.42-6.47 (2m, 1H), 6.54-6.61 (m, 2H), 6.95-7.03 (m, 1H), 7.13- 7.20 (m, 2H), 7.30-7.35 (m, 2H), 7.96 (bs, 2H). LC/MS (III) rt 2.84, m/z 354 (M+H) 3^4(5^Yano-pyridin-2-vtenrwm^ propvU-carbamic acid tert-butvl ester 20 mg (0.05 mmol) [3-(2-aminomethyl-pynrolidii>1-yiyi^^^ carbamic acid tert-butyl ester (step 4, example 50) and 25 pi (0.16 mmol) diisopropylamine are dissolved in 1 mL NMP. 21 mg (0.16 mrnol) of 6- chloronicotinonitrile are added at room temperature. The reaction mixture is stirred for 3 hours at room temperature and for 3 hours at 80 °C. After cooling to room temperature the solvent is evaporated under reduced pressure and the crude product is purified by flash chromatography on silica gel (2% methanol in dichloromethane). LC/MS (II) rt 2.85, m/z 482 (M+H)+. fHCI salt). The product of step 1 is dissolved in 1 mL of 4N hydrochloric acid in dioxane. The solution is stirred for 1 hour at room temperature and the solvent is evaporated under reduced pressure. The crude material is redissolved in methanol and the solvent is evaporated under reduced pressure to give the title compound. LC/MS (II) rt 2.09, m/z 382 (M+H)+. The compounds in Table 10 are synthesized according to the procedure shown for Example 68. ff3ffl^#SHBeireenesutfonvtam propvlT-carbamic acid fejf-butvl ester. Obtained from f3R)-fert-butoxyrarbony)aminc>4^ acid and N- pyrrolidin-^S^ylmethyl'benzensuffonamide (Example 20) according to the procedure described for step 1 in example 32. LC/MS (III) rt 4.98, m/z 542 (M+Na)+. AH1-frefl)-Amino^2-fhKytH^ benzenesutfonarnkte fTFA satt). Obtained from the product of step 1 according to the procedure described for step 2 in example 32. 'H-NMR 5 (ppm) = 1.75-1.85 (m, 4H), 2.48-2.49 (m, 1H), 2.62-2.72 (m, 1H), 2.72-3.04 (mf 3H), 3.22-3.28 (m, 2H), 3.64-3.75 (m, 1H), 3.90-3.94 (m, 0.7H), 4.70 (bs)r 7.09-7.15 (m, 2H), 7.21-7.31 (m, 2H), 750-7.66 (m, 4H), 7.70-7.77 (m, 2H), 7.89 (bs, 1H). LC/MS (III) rt 3.16, m^ 442 (M+Na)+. The compounds in Table 11 are synthesized according to the procedure shown for Example 70. f342-f(3.4-Dimethoxv-benzerre^ benzvtV3-oxcK)ropvlVcarbamic add tert-butvl ester 15 mg (0.04 mmol) [3-(2-amirK>methyl-pynolidin-1-yI>1-(2-fto^ carbamic add tert-butyl ester (step 4, example 51) and 8 pL (0.06 mmol) triethylarnine are dissolved in 1 *iL dichloromethane. 11 mg (0.05 mmol) of 3,4-dimethoxy- benzenesulfonyl chloride are added at room temperature. The reaction mixture is stirred overnight at room temperature and the solvent is evaporated under reduced pressure and the crude product is used in the next step without further purification. /V^143-Amino-4-f2^uoroH3henYl>butw^ benzenesulfonamide fTFA salt). Obtained from the product of step 1 according to the procedure described for step 2 in Example 32. LC/MS (IV) rt 2.21, m/z 480 (M+H)+. n-(2-F)uoro-benzviy3K)xa-f3ft)^ propyR-carbamic acid fe/f-butvl ester. Obtained from ^3R>/e//-butoxyrarbonylarnino-4-(2-fluoro-phenyl)-butyric add and 1- phenyl-3-pyrrolidit>(2S>ylmethyl urea (Example 27) according to the procedure described for step 1 in Example 32. LC/MS (III) rt 4.79, m/z 521 (M+Na)+. 1 -11 -[^3R)-Amino^(2-fluoro-phenvlVbutvrvlVpYrrolidin-^2S)-Ylmethv[>-3-phenvl-urea. Obtained from the product of step 1 according to the procedure described for step 2 in Example 32. 1H-NMR 5 (ppm) = 1.79-1.83 (m, 4H), 2.27-2.31 (m, 1H), 2.67-2.69 (m, 2H), 3.29-3.37 (m, 5H), 3.87 and 3.97 (2m, 1H), 6.20 (m, 0.6H), 6.40 (m, 0.2H), 6.81-6.86 (m, 1H), 7.06-7.39 (m, 8H), 8.41 (bs, 0.5H), 8.52 (bs, 0.2H). LC/MS (III) rt 3.12, mfc 421 (M+Na)*. A/-{1-f^3R)-Aminc>-4-(2-fluoro-phenvn-butvrvn-piperidin-^2S)-vlmethvl>-ben2amidefrFA salt). Obtained from f3R;-fert-butoxycarbonylamino-4-(2-fluoro-phenyl)-butyric acid and N- piperidin-(2S)-ylmethyl-benzamide (example 7) according to the procedure described for Example 32. 1H-NMR 5 (ppm) = 1.25-1.75 (m, 6H), 2.60-3.05 (m, 4H), 3.25-3.55 (m, 4H partially hidden by water signal), 3.65-3.75 (m, 0.5H), 3.95-4.05 (m, 0.5H), 4.28-4.37 (m, 0.3 H), 4.76-4.84 (m, 0.7H), 7.09-7.52 (m, 7H), 7.64 (m, 1H), 7.76-7.94 (m, 4H), 8.25-8.35 (m, 0.7H), 8.55-8.62 (m, 0.3H). AH1-ff3R)-Amino-4-(2-fliK>ro-phenv benzenesutfonamide Obtained from p/?>ferf^toxycarbonylamino^(2»^ acid and A^ pjperklirv(2S>ylmethyl^ (example 25) according to the procedure described for Example 32. LC/MS (II) rt 2.26t mlz 434 (M+H) AK1-f3-Amino^f2-fluoro-phenvlVbuWrvn-piperidirv3-vlmethvtV-benzenesu Obtained from f3R;-ferf-butoxyrarbonylamino-4-(2-fluoro-phenyl)-butyric acid and N- piperidin-3-ylmethyl-benzenesutfonamide (Example 31) according the procedure described for example 32. 1H-NMR 5 (ppm) = 1.05-135 (m, 2H), 1.40-1.75 (m, 3H)r 2.24-2.05 (m, 1H), 2.52-2.75 (m, 4H), 2.80-3.20 (m, 3H), 3.50-3.75 (m, 2H), 4.0CM.12 (m, 0.6H), 4.22-4.35 (m, 0.4H), 7.10-7.20 (m( 2H), 7.26-7.35 (m, 2H), 7.50-7.70 (m, 3H), 7.72-7.74 (m, 2H), 7.85 (bs, 3H). LC/MS (II) rt 2.13, m/z 434 (M+H)+. salt). Obtained from pR>terf^utoxycarbonylamirK4- acid and N- azetjdirv3-yt-methyl-benzylamide (example 8) according the procedure described for example 32. tH-NMR 5 (ppm) = 1.28 (m, 2H), 2.61-2.92 (m, 2H)» 2.95-3.02 (m, 1H), 3.43-3.49 (m, 2H), 3.57-3.70 (mt 2H), 3.74-3.91 (m, 2H), 4.01-4.09 (m, 1H), 7.13^7.19 (m, 2H)t 7.29- 7.32 (m, 2H), 7.38-7.49 (m, 3H), 7.76-7.80 (m, 2H), 7.92 (bs, 3H), 8.51 (m, 1H). LC/MS (II) rt 1.92, mfe 370 (M+H) N41-r3"Amino-4-f2-fluoro-phenvlVbutvrvlVazetidin-3-vlmethvlVbenzenesulfonamide (TFA salt). Obtained from (3/:?)-ferf-butoxycarbonylamino-4-(2«fluoro-phenyl)-butyric acid A/-Azetidin-3-ylmethyI-benzenesulfonamide (Example 30) according to the procedure described for example 32. 1H-NMR 5 (ppm) = 1.20-2.29 (m, 2H), 2.52-2.64 (m, 1H), 2.82-3.03 1-(2^uoro-ltenzYiy3^xo-3^3-p acid tert- butvl ester A mixture of 33.0 mg (0.11 mmol) of (3R)fert-butoxycart>onylamino-4-[2-fluoro-pbenyl]-butyric acid, 16.0 mg (0.21 mmol) of 1-hydroxybenzotriazole, 23.0 mg (0.12 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 114 pi. (0.65 mmol) of diisopropylethylamine in 2.5 mL of DCM is stirred for 5 minutes. After addition of 48.0 mg (0.11 mmol) of 3-phenoxymethyl-azetidine (Example 28), the mixture is stirred overnight The solution is diluted with dichloromethane, washed with a saturated aqueous bicarbonate solution and brine, dried over sodium sulphate and evaporated under reduced pressure. The residue is purified using flash chromatography (silica gel, eluent 25% cyclohexane in ethyl acetate) to afford the title compound. LC/MS (IIS) rt 3.21, m/z 443 (M+H)+. 3-AmirK>4-f2-fluoto-phen>rfH-f3-phenoxw fTFA salt). A solution of 20.0 mg (0.045 mmol) of 1-(2-fluoro-benzyl)-3-oxo-3-(3-phenoxymethyl-azetidin-1-yl)-propyl}-carbamic acid tert-butyl ester in 300 jiL of trifluoroacetic acid and 700 jiL of dichloromethane is stirred at room temperature for 1 h and then evaporated under reduced pressure to give the title compound. 1H-NMR 5 (ppm) = 2.32 (d, 2H), 2.86-3.06 (m, 3H), 3.60-3.70 (m, 3H), 3.8CM.00 (m, 2H), 4.01-4.17 (m, 2H), 6.91 (t, 3H)> 7.15 (t, 2H), 7.23-7.34 (m, 4H), 8.01 (bsf 3H). LC/MS (ID rt 2.35, m/z 343 (M+H)+. The compounds in Table 13 are synthesized according to the procedure shown for Example 92. AH14QR)-Amino^(2-fluoro-phenvl^^ salt). Obtained from (3R>-terM>utoxycarlx>nylamirK>^(^^^ acid and N- plperkJin-S-ylmethyl-benzylamkle (example 9) according to the procedure described for example 32. Prepared as a mixture of diastereomers. LC/MS (II) rt 2.14, m/z 398 (W+H)+. Example 95 Procedure for making an intermediate according to Scheme F. A/-Hvdroxvbenzamidine To 10.31 g (0.10 mol) of benzonitrile dissolved in 40 mL methanol is added 20.73 g (0.15 mole) of finely powdered potassium carbonate. To this is added, in small portions with stirring, 13.89 g (0.20 mol) of hydroxylamine hydrochloride dissolved in 120 mL of methanol. The mixture is then refluxed for 5 hours and, after cooling to room temperature, the solvent is removed under reduced pressure. The residue is taken up in 50 mL of water and 200 mL of chloroform. The organic layer is separated, washed twice with 30 mL of water, and dried over magnesium sulphate. The mixture is then filtered and evaporated under reduced pressure. The residue is crystallised with diethyl ether to afford the title compound. M.P.:77-79°C. 3-Phenvl5-fflchloromethv>-ri .Z41oxacfiazote To 40.05 g (129.7 mmol; 23.7 mL) of trichloroacetic anhydride in a 250 mL round bottom flask protected with a calcium chloride drying tube is added portionwise, with stirring, at room temperature over 20 minutes, 8.82 g (64.80 mmol) of the product from step 1. When addition is complete, the mixture is heated to 90-120°C for 75 minutes, and the hot mixture is then poured into a stirred ice-water solution. The resulting solid is crystallised with hexane or diethylether to give the title compound. 'H-NMR (300 MHz, CDCfe) 8 = 7.60-7.45 (m, 3H), 8.15 (m, 2H). Example 96 Prepared following the procedure outlined for Example 95 according to Scheme F. N-Hydroxvpvridine-2-carboxamide Obtained from pyridine-2-carbonitrile and hydroxylamine hydrochloride according to Step 1 in Example 95. M.P.: 115-117 *C 2-(5-Trichtoromethv»-f 1.2.4toxadiazol3-viy pyridine Obtained from ARiydroxy-pyridine-2-cartx>xamide (Example 96, Step 1) according to Step 2 in Example 95. 'H-NMR (300 MHz, DMSO-ds) 5 = 7.68 (2xdd, 1H), 8.07 (ddd, 1H), 8.14 (dd, 1H), 8.81 (m, 1H). Example 97 Prepared following the procedure outlined for Example 95 according to Scheme F. 3-Chloro-A/-hyctroxv-ben2amicline Obtained from 3-chtorobenzonforile and hydroxylamine hydrochloride according to Step 1 in Example 95. M.P.: 115-118°C 3-(a^htorophenvtyS-trk^toromethyHI .2.4fcxadiazote Obtained from 3-chk>rxvA^ydroxy4)enzarnldine (Example 97, Step 1) according to Step 2 in Example 95. 1H-NMR (300 MHz, CDCfe) 5 = 7.44 (dd, 1H)> 7.55 (ddd, 1H), 8.04 (ddd, 1H), 8.12 (ddt 1H). Example 98 Prepared following the procedure outlined for Example 95 according to Scheme F. ■ 3-Ruoro-A/-hvdroxv-benzamidine Obtained from 3-fluorobenzonitrile and hydroxylamine hydrochloride according to Step 1 in Example 95. M.P.: 74-76°C 3-(3-FliKirophenvn-&'trichlorDm^hvH1.2.4Toxadiazole Obtained from 3-fluoro-N-hydroxy-benzamidine (Example 98, Step 1) according to Step 2 in Example 95. 1H-NMR (300 MHz, CDCfe) 6 = 7.26 (m, 1H), 7.51 (m, 1H), 7.75 (m, 1H), 7.93 (m, 1H). Example 99 Prepared following the procedure outlined for Example 95 according to Scheme F. A^Hvdroxv-4-methanesulphonvt4)en2amidine Obtained from 4-methanesulphonyl-benzonitrile and hydroxytamine hydrochloride according to Step 1 in Example 95. M.P.:115-118°C 3-f4*Methanesulphonvh3henvlV5-trichtorpm ,2.41oxadiazole Obtained from A^hydroxy-4-methanesulphonyl-benzamidine (Example 99, Step 1) according to Step 2 in Example 95. 1H-NMR (300 MHz, CDCI3) 5 = 3.13 (s, 3H), 8.12 and 8.38 (m, 4H). Example 100 Following examples are prepared according to Schemes G and H. (2SH3-Phenvt-f 1.2.41oxadiazol5-vlarniro acid tert- butvl ester 164.40 mg (0.62 mmol) of S-phenyl-S-trichtoromethyKiloxadiazole (Example 95) and 150.0 mg (0.75 mmol) of (2S)-aminom6thyl-pyrrolidine-1-carboxylic acid tert-butyl ester is stirred in 5 mL of dry N,N-dimethyfformamide at 60 °C for 12 hours. The progression of the reaction is monitored by TLC (Kieselgel Merck 5554 sheets, eluent hexane-ethyfacetate 2:1). The mixture is evaporated to dryness under reduced pressure and the residue is purified by preparative thin layer-chromatography using the same solvent system to afford the title compound. 1H-NMR (300 MHz, CDCI3) 8 = 1.45 (s, 9H), 1.62-2.16 (m, 4H), 3.2^3.70 (m, 4Ht), 4.17 (m, 1H), 7.30 (m, 1H), 7.41 (m, 3H), 7.90 (m, 2H). (^Phenyl-[1 l2l4]oxadiazol-5»yl)pyrrolidin-(2S)-ylmethyIamine hyclrochloride The product from Step 1, (2SH3-ph^y*-[1»2l4}oxadiazol»5-ylamino)-methyl]pyrrolidine-1-carboxylic acid tert-butyl ester, is dissolved in 4 mL of dichloromethane then 8 mL of saturated HCI/dioxane solution is added. After the mixture is stirred for 2 hours the solvent is evaporated under reduced pressure to yield the title compound, which is used directly in the next step without further purification and characterisation. (1ffl-(2-FluorobenzvlV3-oxo-34(2SVf(3-phenvl-f1.2.41oxadiazol-5-vlamino-methvnpvrrolidin-1-vlVpropvl)carbamic acid ferf-butvl ester tn a 25 mL round-bottomed flask is stirred for 2 hours under nitrogen a mixture of 74.90 mg (0.38 mmol) of (3R)-terf^utoxycarbonylamino^(2-fluoro^henyI)-butyric and 64.70 mg (0.40 mmol; 1.05 eq.) of 1,1'-carbonyldiimidazole in 5 mL of dry 1,2-dichloroethane. Separately, 106.70 mg, (0.38 mmol) of 3-phenyl-[1,2,4]oxadiazol-5-yi)pyrro!idin-(2S)-ylmethylamine hydrochloride (Example 100, Step 2) and 107.90 mg, (0.83 mmol; 145.0 ^L; 2.2 eq.) of /V.AWiisopropylethylamine is stirred in 4 mL of dry 1,2-dichloroethane for 15 minutes and this solution is poured into the butyric add and 1,1'-carbonyldiimidazole reaction mixture prepared above. Stirring is continued overnight at room temperature, then the mixture is boiled for 5 hours. The solution is cooled to room temperature, washed successively with a 5 % citric acid solution, saturated sodium hydrogen carbonate solution, water and brine, dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is subjected to preparative thin layer chromatography on silica gel (eluent; dichloroethane/ethanol 5:1) to afford the title compound which is taken directly into the next step without further characterisation. f3ffl"Amino-^f2-fluorophenvlV14f2S>-rf3-phenvl-fl2.41oxadiazol-5"Vlamino)-methvl]-pvrrolidin-1-vlVbutan-1-one hvdrochloride (1R)-(2-fluorobenzyl)-3-oxo-3-{(2S)-[(3-phenyl-[1,2l4]oxadia2ol-5-ylaminO"methyl]-pyrrolidin-1-yl}-propyl)carbamic acid tert-butyl ester, the product from Step 3, is dissolved in 4 mL of dichloromethane then 10 mL of saturated HCI/dioxane solution is added. The mixture is stirred for 2 hours then is the solvent removed under reduced pressure to yield the title compound. If the residue is a solid it is taken up in diethyl ether and hexane and filtered. Otherwise, if the residue is an oil, this is taken up in 10 mL of dioxane and the solvent is evaporated to dryness. This procedure is repeated two times to afford the title compound. 1H-NMR (300 MHz, CDCI3) 8 = 1.82-2.00 (m, 4H), 2.66-2.70 (m, 1H), 2.84 (bs, 1H), 3.21 (bs, 1H), 3.33-3.53 (m, 5H), 4.01 (bs, 1H), 4.39 (bs, 1H), 6.92-7.03 (m, 2H), 7.13- 7.21 (m, 1H), 7.32-7.47 (m, 3H), 7.58 (bs, 1H), 7.8&-7.90 (m, 2H), 7.94-8.06 (m, 1H), 8.66 (m, 3H). LC/MS (Method VII) m/z 424 [M+H]*. Prepared according to the procedure above outlined for Example 100 Steps 1 to 4, according to Schemes G and H. (2SH(3-Pvridh>2-vl-ri .2.41oxadiazot-5-vlamhoVmethvn-PvrrDlidine-1-carboxvlic acid terf-butvl ester Obtained from 2-(5-trichloromethyl-[1,2,4]oxadiazol-3-yl>-pyridine (Example 96) and (2S)-aminomethyl-pyrroIidine-1-carboxylic acid terf-butyl ester? synthesised according to the procedure for Example 100, Step 1. 1H-NMR (300 MHz, CDCI3) 6 = 1.45 (s, 9H), 1.60-2.20 (mf 4H), 3.20-3.45 (m, 4H), 4.15 (m, 1H), 7.38 (m, 1H), 7.50 (m, 1H), 7.79 (ddt 1H), 8.08 (dd, 1H)f 8.78 (dd,1H). Step 2 (3-Pvridin-2-vl-f 1.2.41oxadiazo^&'VlVpvrrolkiir>^S^vlmethvtamir^ dt-hvdrochtoride Obtained from ^SHfS-Pyridin^-yKI^Joxadiaz^ carboxylic acid fe/f-butyl ester (Example 101, Step 1), and synthesised according to the procedure for Example 100, Step 2. (1/?H2-nuorobenzvn-3^xo^^ methvnHJvrroltdirvi-vtVpropvlH^rbamicacid terf-butvl ester Obtained from (3^yrkJirv2-yKi,2,4]oxadto^ di- hydrochloride (Example 101, Step 2) and (3R>tert-lxrtoxy(^rt)onylamJno-4-(2-fluoro- pheny!)-butyric acid, and synthesised according to Example 100, Step 3. (3/?VAmino^-f2-fluorophenvl)-Hf2S)-rf3-pyridin-2"VK12.41oxadiazol"5-vlamino)-methvli-pyrTolidifv 1 -vD-butan-1 -one. Di-hvdrochloride Obtained from (1/?)-(2-fluorobenzyl)-3-o)a)-3-{(2^-[(3-pyridin-2-yl-[1l2,4]oxadiazol-5- ylamino)-methyO-pyrrolidin-1-yl}-propyl)-carbam»c acid ferf-butyl ester (Example 101, Step 3), and syrtthesised according to Example 100, Step 4. 1H-NMR (300 MHz, CDCI3 + DMSO-d6) 5 = 1.88-1.99 (m, 4H), 2.50-2.58 (m, 1H), 2.62- 2.68 (m, 1H), 2.97-3.03 (m, 1H), 3.12-3.17 (m, 1H), 3.33-3.40 (m, 3H), 3.50-3.54 (m, 1H), 3.70-3.74 (m, 1H), 4.25-4.27 (m, 1H), 7.04-7.16 (m, 2H), 7.24-7.35 (m, 2H), 7.53- 7.58 (m, 1H), 7.95-8.06 (m, 2H), 8.19-8.24 (bs, 3H), 8.43-8.46 (m, 1H), 8.70-8.76 (m, 1H). LC/MS (Method VII) m/z 425 [M+Hf Prepared according to the procedure above outlined for Example 100, steps 1-4 according to Schemes G and H. (2SHT3-(3 acid te/f-butvl ester Obtained from S-^a-Chlorophenyl^S-trichlorDmethyKi^^loxadiazole (Example 97) and (2S>-aminomethyl-pyrrolidine-1-carboxylic acid ferf-butyl ester, synthesised according to the procedure for Example 100, Step 1. r3-(3-ChlorophenvlH1.2.41oxadiazol5-vn^ Obtained from (2S)-{[3-(3-chlorophenylH1.2,4]oxadiazol-5-ylamino]-methyl}- pyrrolidine-1-carboxylic acid terf-butyl ester (Example 102, Step 1), and synthesised according to the procedure for Example 100, Step 2. 1H-NMR (300 MHz, CDCi3 + de-DMSO) 8 = 1.75-2.20 (m, 4H)f 3.20-3.30 (m, 2H), 3.71 (m, 2H), 3.81 (m, 1H), 7.40-7.50 (m, 2H), 7.85 (ddd, 1H), 7.88 (dd, 1H), 8.57 (m, 1H), 9.00 and 9.42 (bm, 2H). r3-f2SHT3-(3-ChtorophenvtH1.2>41oxadiazol-5'YlaminoT-methvlVH3viTDlidirv1-Yn-n Ri- g^uorDbenzvtVa^xo-PfopvlVcarbarnk: acid terf-butvl ester Obtained from [3-(3-chk>rophenylH1»2r4]oxadia^ hydrochloride (Example 102, Step 2) and (3R)-tert-lxitoxycarbonylamino-4-(2-fhjort>- phenyl)~butyric acid, and synthesised according to Example 100, Step 3. 1H-NMR (300 MHz, CDCI3) 5 = 1-38 (s, 9H), 1.80-2.10 (mf 4H), 2.50 and 2.90 (m, 2 x 2H), 3.20-3.70 (m, 4H)t 4^3 (m, 1H), 4.38 (m, 1H), 5.38 (m, 1H), 7.00-7.25 (m, 4H), 7.32 (bmr), 7.35 (m, 1H), 7.42 (m, 1H), 7.87 (ddd, 1H), 7.97 (dd, 1H). f3ffW^ino-1-(2S)-ff3-(3Kfrk>rDphen^ vlV4-(2-fluorophenvn-butan-1-one hvdrochloride Obtained from [3-(2S)-{[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylamino]-methyl}- pyrrolicfirv1-yl)-(1/^(2-fluorobenzyI)-3-ox(>propylfcarbamic acid fe/f-butyl ester (Example 102, Step 3), and synthesised according to Example 100, Step 4. 1H-NMR (300 MHz, CDCb) 5 = 1.82-1.99 (m, 4H), 2.67-2.73 (m, 1H), 2.83-2.89 (m, 1H), 3.21-3.25 (m, 1H), 3.39-3.53 (m, 5H), 3.99-4.03 (m, 1H), 4.40-4.42 (m, 1H), 6.93- 6.97 (m, 1H), 7.00-7.04 (m, 1H), 7.14-7.19 (m, 1H), 7.21-7.40 (m 3H), 7.59 (bs( 1H), 7.76-7.78 (m, 1H), 7.87 (s, 1H), 8.66 (bs, 3H). LC/MS (Method VII) m/z 458 [M+Hf Prepared according to the procedure above outlined for Example 100, steps 1-4, according to Schemes G and H. (2Sy^3-(3-HuorophenvtH1.2.41o acid fe/f-butvl ester Obtained from 3-(3-fluorophenyl>-S-trichlon>meth^t1,2I4loxadia2X)le (Example 98) and ^S)-aminomethyl-pyrrolidir^-1-carboxylJcacid ferf-butyi ester, synthesised according to the procedure for Example 100, Step 1. [3-f3-Fluoix>phenvn-ri2141oxadiazol"5"Vn-pvnr>lidirh(2SVvlmethvlarnine hvdrochloride Obtained from (2S)-{[3-(3-Fluorophenyl>-[1,2,4]oxadiazol-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid ferf-butyl ester (Example 103, Step 1), and synthesised according to the procedure for Example 100, Step 2. 1H-NMR (300 MHz, CDCI3 + dg-DMSO) S = 1.75-2.20 (m, 4H), 3.10-3.38 (m, 2H), 3.69 (m. 2H), 3.81 (m, 1H), 7.25 (m, 1H), 7.48 (m, 1H), 7.66 (ddd, 1H), 7.78 (dd, 1H), 8.62 (1H, mf NH), 8.90 and 9.42 (bm, 2H). OT RH2-FluorobenzvlV3-((2SHr3-(3-fluorophenvlVf 1,2.4Toxadlazoi-&-vlaminoT-methv{V- pvrrortdirvi-vlVS-oxoHPropvft-carbamic acid terf-butvl ester Obtained from [3-(3^uoiT)phenylH1.2,4loxadiaz^^ hydrochloride (Example 103, Step 2) and (3R)-tert4)utoxycartx)nylamino^2-fkioro- phenylVbutyric acid, and synthesised according to Example 100, Step 3. (3/?Wkmtno-4-(2-fluoroohenviyi^ methvl)H3vrit)tidii>1-vlVbutan-1-one hvdrochloride Obtained from [(1 /?H2-fluorobenzyl)-a-((2SH[3-(3-fluorophenylH1,2t4]oxadiazol-5-ylamino]-methyl}-pyrrolJdh-1-yD-3^x&pro|^0K3rbamic acid terf-butyl ester (Example 103, Step 3), and syrrthesised according to Example 100, Step 4. 1H-NMR (300 MHz, CDCfe) 8 = 179-2.06 (m, 4H), 2.73-2.83 (m, 2H), 3.21-3.27 (m, 1H), 3.38-3.54 (m, 3H), 3.58-3.72 (m, 2H), 3.97-4.05 (m, 1H), 4.42-4.49 (m, 2H), 6.93-6.97 (m, 1H), 7.01-7.04 (m, 1H), 7.12-7.17 (mt 2H), 7.30-7.41 (m, 2H), 7.62-7.65 (m, 1H), 7.74-7.76 (d, 1H), 8.32 (bst 1H), 8.62 (bs, 3H). LC/MS (Method VII) m/z 442 [M+Hf Prepared according to the procedure above outlined for Example 100, steps 1-4, according to Schemes G and H. (2SHP^44fethanesutPhonv^^ carboxvtic acid tort-butyl ester Obtained from 3-(4nrnethanesulphony (Example 99) and pS)minomethyl-pyrroBdBrie-1-carbo)^ic acid ferf-butyt, synthesised according to the procedure for Example 100, Step 1. 1H-NMR (300 MHz, CDCfe) 6 = 1.45 (s, 9H), 1.60-2.18 (m, 4H), 3.05 (sf 3H), 3.25-3.70 (m, 4H), 4.17 (m, 1H), 7.46 (m, 1H), 8.00 (m, 2H), 8.20 (m, 2H). f3-(4-Methanesulphonvtph^ hvdrochloride Obtained from (2S)^3^4-rnethanesulphonylpbenyfH1»2,4]oxadiazol-5-ylamino]-methyl)-pyrrolidine-1-carboxylic add ferf-butyl ester (Example 104, Step 1), and synthesised according to the procedure for Example 100, Step 2. rn/?H2-nuorobenzyiy:^(2SHr^ vlaminoVmethvl)HPvm>lkf^ acid ferf-butvl ester Obtained from [3~(4-methanesulphony!phenylH1^^ ylmethylamine hydrochtoride (Example 104, Step 2) and (3R)-tert- butoxycarbonylamino-4-(2-fluoro-phenyl)-butyric acid, and synthesised according to Example 100, Step 3. (3ffWAmino-4^2-fluorophCTV^ f1.2.41oxadiazol5-vlaminoyn^^ hvdrochloride Obtained from [(1/^2-Ruorobenzyl)-3^ [1 ^,4]oxadiazol-5-ylamirK>l-methyl}^ acid tert- butyl ester (Example 104, Step 3), and synthesised according to Example 100, Step 4. 1H-NMR (300 MHz, CDCfe) 5 = 1.80-2.03 (m, 4H), 2.75-2.81 (m, 2H), 3.07 (s, 3H), 3.21-3.27 (m, 1H)f 3.34-3.55 (m, 4H), 3.60-3.68 (m, 1H), 3.96-4.06 (m, 1H), 4.43-4.50 (m, 1H), 6.94-6.98 (m, 1H), 7.02-7.05 (m, 1H), 7,16-7.21 (m, 1H), 7.30-7.34 (m, 1H), 7.98 (d, 2H). 8.14 (d, 2H)( 8.35 (bs, 1H), 8.64 (bs, 3H). LC/MS (Method VII) m/z 502 [M+Hf. The following compound (example 105) was prepared according to the following experimental procedure: To 200 pL of a 0.6M A/,Akiimethytforrnamide solution of (3R)-tert~ butoxycarbonylamino-4-[2-fluoro-phenyl>butyric acid including 1.5 eq of triethylamine in a well of a 96-microtiterplate (96-MTP) 200 pL of a 0.6M tyAMimethyfformamide solution of 0(benzotrialzoM-YL)-N-N-N ,N -tetramethyluronium hexafluorophosphate (HBTU) are added. After 15 min. at room temperature, 200 pL of a 0.5M NtN-dimethytformamide solution of the corresponding amine and 11 pL (0.15 mmol) of N-methylmorpholine are added and the reaction mixture is stirred overnight at 50°C. Solvents are removed under reduced pressure, 500 pL of a solution of trifluoroacetic acid in dichbromethane (33% v/v) is added and the reaction mixture is stirred for 2 h at room temperature. After removal of the solvents under reduced pressure, 500 pL of methanol are added and the crude material is purified using preparative HPLC with a 10 min. linear gradient from 5% to 95% acetonrtrile in water (0.1% TFA) to afford the title compounds. 3-Amino^(2-fluorc>-phenvn-1'f3-hvdroxvmethvl-piperidin-1-vlVbutan-1-one LC/MS (V!) (1-30%, 8 min) rt 5.28, m/z 295 (M+H)+. Further examples from this series are exemplified below: ASSAYS Inhibition of DPP-IV peptidase activity was monitored with a continuous fluorimetric assay. This assay is based on the cleavage of the substrate Gly-Pro-AMC (Bachem) by DPP-IV, releasing free AMC. The assay is carried out in 96-wetl miorotiterplates. In a total volume of 100 pL, compounds are preincubated with 50 pM DPP-IV employing a buffer containing 10mM Hepes, 150mM NaCI, 0.005% Tween 20 (pH 7.4). The reaction is started by the addition of 16 pM substrate and the fluorescence of liberated AMC is detected for 10 minutes at 25 °C with a fluorescence reader (BMG-Fluostar; BMG-Technologies) using an excitation wavelength of 370 nm and an emission wavelength of 450 nm. The final concentration of DMSO is 1 %. The inhibitory potential of the compounds were determined. DPP-IV activity assays were carried out with human and porcine DPP-IV (see below); both enzymes showed comparable activities-include. Soluble human DPP-IV lacking the transmembrane anchor (Gly31-Pro766) was expressed in a recombinant YEAST-strain as Pre-Pro-alpha-mating fusion. The secreted product (rhuDPP-IV-Gly31-Pro766) was purified from fermentation broth (>90% purity) and used for inhouse screening. Claims 1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein Z is selected from the group consisting of phenyl; naphthyl; C3-7 cydoalkyl; heterocyde; and heterobicyde; wherein Z is optionally substituted with one, or independently from each other, more of halogen; CN; OH; =O, where the ring is at least partially saturated; C-j^ alkyl, optionally substituted with one or more F; and O-C1-6 alkyl, optionally substituted with one or more F; R1, R2, R4, R5 are independently from each other selected from the group consisting of H; F; OH; C-i-6 alkyl, optionally substituted with one or more F; and O-C1-6 alkyl, optionally substituted with one or more F; and/or R1 and R2 optionally form together C3.7 cycloalkyl, which is optionally substituted with one or more F; and/or R2 and R3 optionally form together C3-7 cycloalkyl. which is optionally substituted wfth one or more F; and/or R3 and R4 optionally form together C3-7 cycloalkyl, which is optionally substituted with one or more F; and/or R4 and R5 optionally form together C3-7 cycloalkyl, which is optionally substituted with one or more F; R3 is H or C1-6 alkyl; X is selected from the group consisting of H; F; and C1-8 alkyl, optionally substituted with one or more F; nisO, 1 or 2; A1, A2 are independently from each other selected from the group consisting of H; halogen; C1-6 alkyl, optionally substituted with one or more F; and R6; provided that one of A1 and A2 is R6; R6 is -C(R7R8)-Y-T; R7, R8 are independently from each other selected from the group consisting of H; F;and C1-6 alkyl, optionally substituted with one or more F; and/or R7 and R8 optionally form together C3-7 cycloalkyl, which is optionally substituted with one or more F; Y is selected from the group consisting of -Os -C1-4 alkyl-O; -NfR9)-; -C1-6 alkyl-NfR9)- -S-; -c1-c6 alkyl-S-; -S(0)-; -c1-c4 alkyl-S(O)-; -S(0)2-; and -C1-6 alkyl-S(o)2; wherein each c1-4* alkyl is optionally substituted with one or more F; R8, T are independently from each other T1-T2 or T2; V is selected from the group consisting of -c1-c4 alkyl-; -C1-C4 alkyl-O- -C1-6 alkyl-N(R10)- -C(O)-; -c(O)-C1-6 alkyl; -C(O)-C1-4 alkyl-O-; -C(O)-C1-4 alkyl-N(R10)--; -C(O)O-; -C(O)O-C1-6 alkyl-; -0(0)0-c1-6 alkyl-o-; -C(0)0-C1-6 alkyl-N(R10)-; -C(O)N(R10)-; -C(o)N(R10)C1-6 alkyl; -C(O)N(R10)-C1-6 alkyl-O; -C(O)N(R10)-C1-6 alkyl-N(R11)-; -S(0)r; -8(0)2-c1-6 alkyl-; -S(O)z-C1-6 alkyl-O-; and S{0)z-C1-6 alkyl-N(R10)-; wherein each C1-6 alkyl is optionally substituted with one or more F; R10, R11 are independently from each other H or c1-6 alkyl, optionally substituted with one or more F; T2 is selected from the group consisting of H; CF3; phenyl; naphthyl; wherein phenyl and naphthyl are optionally substituted with one, or independently from each other, more of halogen; CN; R12; COOH; OH; C(O)NH2; S(O)2NH2; COOT*; OT3; C(O)NHT3; S(O)2NHT3; or T3; C3.7 cycloalkyl; heterocyde; and heterobicycle; wherein C3.7 cycloalkyl, heterocyde and heterobicycle are optionally substituted with one, or independently from each other, more of halogen; CN; R13; OH; =0, where the ring is at least partially saturated; NH2 COOH; C(O)NH2; S(O)2NH2; COOT3; OT3; C(O)NHT3; S(O)2NHT3; NHT3; or T3; whereby when R9 is T1-T2 and represents -C1-6 alkyl and T is T1-T2 and represents -C1_6 alkyt then R9 and T may form together a 3 to 7 membered cyclic group containing 1 N; R12 is selected from the group consisting of C1-6 atkyl; O-C1-6 alkyl; COO-C1-6 alkyl; OC(O)- c1-6 alkyl; C(O)N(R15)- c1-6 alkyl; S(O)2N(R17)-C1-6 alkyl; S(o)-c1-6 alkyl; S(O)2-Ci-s alkyl; and N(R18)S(o)2-c1-6 alkyl; wherein each C1-6 alkyl is optionally substituted with one, or independently from each other, more of F, COOR19, C(o)N(R20R21), S(O)2N(R22R23), OR24, N(R25R26), T3, OT3 or N(R27)-T3; R13 is selected from the group consisting of C1-.6 alkyl; O-C1-.6 alkyl; N(R14)-C1-6 alkyl; COO-C1-6 alkyl; OC(O)- C1-6 alkyl; C(O)N(R15)- C1-6 alkyl; N(R16)-C(O)-C1-6 alkyl; S(O)2N(R17)-C1-6 alkyl; S(O)-C1-6 alkyl; S(O)2-C1-.6 alkyl; and -N(R18)S(O)2-C1-6 alkyl; wherein each C1-6 alkyl is optionally substituted with one, or independently from each other, more of F, COOR19, C(O)N(R20R21), S(O)2N(R22R23), OR24, N(R25R26), T3, O-T3 or N(R27)-T3; R14, R15, R16, R17, R18, R19, R20. R21, R22, R23, R24. R25, R26, R27 are independently from each other H or C1-6 alkyl; T3 is selected from the group consisting of phenyl; naphthyl; wherein phenyl and naphthyl are optionally substituted with one, or independently from each other, more of halogen; CN; COOH; OH; C(O)NH2; C1-6 alkyl; O-C1-6alkyl; COO-C1-6 alkyl; OC(O)- C1-6 alkyl; C(O)NfR28)- C1-6 alkyl; S(O)2R29C1-6 alkyl; S(O)2-C1-6 alkyl; or N(R30)S(O)-C1-6 alkyl; heterocycle; heterobicycle; and C3.7 cycloalkyl; wherein C3.7 cycloalkyl, heterocycle and heterobicycle are optionally substituted with one, or independently from each other, more of halogen; CN; OH; =O, where the ring is at least partially saturated; NH2 COOH; C(O)NH2; S(O)2NH2; C1-6 alkyl; O-C1-6 alkyl; N(R31)-C1-6 alkyl; COO-C1-6 alkyl; OC(O)- C1-6 alkyl; C(O)N(R32)- C1-6 alkyl; N(R33)-C(O)-C1-6 alkyl; S(O)2N(R34)-C1-6alkyl; S(O)2-C1-6 alkyl; or -N(R36)S(O)2-C1-6 alkyl. 2. A compound according to claim 1 of formula (la) or a pharmaceutically acceptable salt thereof, wherein Z, R1-R5, A1, A2, n and X have the meaning as indicated in claim 1. 3. A compound according to claim 1 or 2, wherein Z is phenyl or heterocycle and Z is optionally substituted independently from each other with up to 2 of Cl, F, CN, CH3 or OCH3. 4. A compound according to any one of the preceding claims, wherein R1, R2, R4, Rs are independently from each other selected from the group consisting of H, F, OH CH3l OCH3. 5. A compound according to any one of the preceding claims, wherein R3 is H. 6. A compound according to any one of the preceding claims, wherein X is H, F or CH3. 7. A compound according to any one of the preceding claims, wherein n is 1. 8. A compound according to any one of the preceding claims, wherein A1 is R6 and A2 is H, F or CH3. 9. A compound according to any one of the preceding claims, wherein R6 is -CH2-Y-T. 10. A compound according to any one of the preceding claims, wherein Y is -O-, -N(R3) or -S(O)2-. 11. A compound according to any one of the preceding claims, wherein R9 is selected from the group consisting of H, CH3, COOH. COOCHa, C(O)NH2, C(O)N(CHa)2, and S(O)2CH3. 12. A compound according to any one of the preceding claims, wherein T is f-T2 or T2 and wherein T1 is selected from the group consisting of -CHr; -C(O)-; -C(O)-CH2-; -C(O)O-; -C(O)O-CH2-; -C(O)NH-; -C(O)NH-CH2-; -S(O)2-; and -S(O)2-CH2-. 13. A compound according to claim 12, wherein T is T1-T2 or T2 and wherein T1 is selected from the group consisting of -C(O)-; -CHr; -S(O)2-; and -C(O)NH-. 14. A compound according to any one of the preceding claims, wherein R6 is -CH2-N(R36)-T, and wherein R36 is H or S(O)2CH3. 15. A compound according to any one of the preceding claims, wherein T2 is phenyl or heterocycle. 16. A compound according to claim 1 selected from the group consisting of or a pharmaceutical^ acceptable salt thereof. 17. A prodrug compound of a compound according to any one of the claims 1 to 16. 18. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to any one of the claims 1 to 17 together with a pharmaceutically acceptable carrier. 19. A pharmaceutical composition according to claim 18, comprising one or more additional compounds or pharmaceutically acceptable salts thereof selected from the group consisting of another compound according to any one of the claims 1 to 17; another DPP-IV inhibitor, insulin sensitizers; PPAR agonists; biguanides; protein tyrosinephosphatase-lB (PTP-1B) inhibitors; insulin and insulin mimetics; sulfonylureas and other insulin secretagogues; a-glucosidase inhibitors; glucagon receptor antagonists; GLP-1, GLP-1 mimetics, and GLP-1 receptor agonists; GiP, GIP mimetics, and GIP receptor agonists; PACAP, PACAP mimetics, and PACAP receptor 3 agonists; cholesterol lowering agents; HMG-CoA reductase inhibitors; sequestrants; nicotinyl alcohol; nicotinic acid or a salt thereof; PPARa agonists; PPARoly dual agonists; inhibitors of cholesterol absorption; acyl CoA : cholesterol acyltransferase inhibitors; anti-oxidants; PPARo agonists; antiobesity compounds; an ileal bile acid transporter inhibitor; and anti-inflammatory agents. 20. A compound or a pharmaceutically acceptable salt thereof of any one of the claims 1 to 17 for use as a medicament. 21. Use of a compound or a pharmaceutically acceptable salt thereof of any of the claims 1 to 17 for the manufacture of a medicament for the treatment or prophylaxis of non-insulin dependent (Type II) diabetes mellitus; hyperglycemia; obesity; insulin resistance; lipkl disorders; dyslipidemia; hyperlipidemia; hypertriglyceridemia; hypercholestrerolemia; low HDL; high LDL; atherosclerosis; growth hormone deficiency; diseases related to the immune response; HIV infection; neutropenia; neuronal disorders; anxiety; depression; tumor metastasis; benign prostatic hypertrophy; gingivitis; hypertension; osteoporosis; diseases related to sperm motility; kyw glucose tolerance; insulin resistance; ist sequelae; vascular restenosis; irritable bowel syndrome; inflammatory bowel disease; including Crohn's disease and ulcerative colitis; other inflammatory conditions; pancreatitis; abdominal obesity; neurodegenerative disease; retinopathy; nephropathy; neuropathy; Syndrome X; ovarian hyperandrogenism (polycystic ovarian syndrome; Type n diabetes; or growth hormone deficiency. 22. Use of a compound according to any one of the claims 1 to 17 as DPP-IV inhibitor. 23. Process for the preparation of a compound according to any one of the claims 1 to 17, comprising the steps of • coupling of an amino-protected beta-amino acid of formula (IVa) wherein PG is a protective group, with an amine of formula (III) using standard peptide coupfing oondMons, reagents and protective groups; • removing the protective group (PG). 24. A process according to daim 23, vrtierein tie oouping reagents are 1-ethyl-S-(3- dimrthyiaminopropyl)carbodimide hydrochloride (EDC) in combination with 1- hydruxybenzotriazcte (HOBQ and a base (triethylamine or disopropylethylamine)or o-(7-azabenz0triazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) in the presence of a base and the protective group is 9-fluorenylmethoxycarbonyl or tert-butoxycarbonyl. 25. A process according to claim 23 or 24, wherein the protective group is removed using diethyiamine in dichkxomethane in the case of 9-fluorenylmethoxycarbonyl or using acidic conditions in the case of ferf-butoxycarbonyl. 26. A compound, a prodrug compound, a pharmaceutical composition, use of a compound and a process for the preparation of a compound substantially as herein described with reference to the foregoing examples.

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