Claims for Patent: 7,220,862

Summary for Patent: 7,220,862

Title:	Calcitonin gene related peptide receptor antagonists
Abstract:	The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.
Inventor(s):	Prasad V. Chaturvedula, Ling Chen, Rita Civiello, Andrew P. Degnan, Gene M. Dubowchik, Xiaojun Han, Xiang Jun J. Jiang, George N. Karageorge, Guanglin Luo, John E. Macor, Graham Poindexter, George Tora
Assignee:	Bristol Myers Squibb Co
Application Number:	US10/729,155
Patent Claims:	1. A compound according to Formula (I) or a pharmaceutically acceptable salt thereof wherein V is —N(R1)(R2) or OR4; R4 is H, C1-6alkyl, C1-4haloalkyl or (C1-4alkylene)0-1R4′ R4′ is C3-7cycloalkyl, phenyl, adamantyl, quinucidyl, azabicyclo[2.2.1]heptyl, azetidinyl, tetrahydrofuranyl, furanyl, dioxolanyl, thienyl, tetrahydrothienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyranyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino or dioxolanyl; and R4′ is optionally substituted with 1 or 2 of the same or different substituents selected from the group consisting of halo, cyano, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, hydroxy, amino, C3-7cycloalkyl, C1-3alkylamino, C1-3dialkylamino, (C1-3alkyl)0-2ureido, phenyl and benzyl; and R4′ optionally contains 1 or 2 carbonyls wherein the carbon atom of said carbonyl is a member of the ring structure of R4′; R1 and R2 are each independently L1, wherein L1 is selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, —C1-6alkylene-amino (C1-3alkyl)2, C3-7cycloalkyl, phenyl, azetidinyl, adamantyl, tetrahydrofuranyl, furanyl, dioxolanyl, thienyl, tetrahydrothienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, triazolyl, pyranyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino and dioxolmnyl; and R1 and R2 are each optionally and independently substituted with 1 or 2 of the same or different substituents selected from the group consisting of halo, cyano, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, hydroxy, amino, C3-7cycloalkyl, C1-3alkylamino, C1-4dialkylamino, (C1-3alkyl)0-2ureido, phenyl and benzyl; R1 and R2 optionally and independently contain 1 or 2 carbonyls wherein the carbon atom of said carbonyl is a member of the heterocycles comprising R1 and R2; wherein L1 is optionally and independently interrupted from the nitrogen to which it is attached by L2, wherein L2 is independently C1-3alkylene or C1-3alkylidene; or R1 and R2 together with the nitrogen to which they are attached form X, wherein X is azetidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolizyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, azepinyl, diazepinyl, piperazinyl, piperidinyl, morpholino or thiomorpholino; wherein X is optionally substituted with Y, wherein Y is dioxolanyl, C1-9alkyl, C2-9alkenyl, C2-9alkynyl, C1-4alkylamino, C1-4dialkylamino, C1-4alkoxy, C3-7cycloalkyl, phenyl, azetidinyl, furanyl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, imidazolyl, imidazolinyl, imidazolidinyl, imidazolidinonyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, azepinyl, diazepinyl, pyridyl, pyrimidinyl, dihaydrobenzimidazolonyl, piperazinyl, piperidinyl, morpholino, benzothiazolyl, benzisothiazolyl or thiomorpholino; and wherein X and Y are optionally interrupted with Z, wherein Z is—NHC(O)O—, —NHC(O)NH—, NC(Q)NH2,—NH—, —C1-3alkylene—, C1-3alkenylene-NHC(O)O—C1-3alkylene-; and optionally and independently substituted with 1 or 2 of the same or different substituents selected from the group consisting of C1-4alkyl, amino, C1-3alkylamino, —C1-3alkylene-amiao(C1-3alkyl)2, (C1-3alkyl)0-2ureido, phenyl and benzyl; X and Y optionally and independently contain 1 or 2 carbonyls wherein the carbon atom of said carbonyl is a member of the heterocycles comprising X and Y; provided that if X is substituted with Y, and if X and Y are not interrupted with Z, then X and Y optionally share one carbon atom and together form a spirocyclic moiety; Q is Q′ or Q″; wherein Q′ is (Sy)SR3; and Q″ is NH(Sy)SR3, NHC(O)(Sy)SR3, NHC(O)O(Sy)SR3, NHC(O)NH(Sy) sR3, O(Sy)SR3, (Sy)3NHR3, (Sy)SNHC(O)R3,(Sy)SNHC(O)OR3, (Sy)SNHC(O)NHR3; or (Sy)SOR3; wherein Sy is C1-3alkylene or C1-3alkylidene and a is 0 or 1; U is CH2 or NH; provided that if Q is Q″, then U is CH2; R3 is R3a or R3b wherein R3a is (i) a heterocycle having two fused rings with 5 to 7 members in each of said rings, said heterocycle containing one to five of the same or different beteroatoms selected from the group consisting of O, N and S, and said heterocycle optionally containing 1 or 2 carbonyls wherein the carbon atom of said carbonyl is a member of said fused rings; (ii) a 4 to 6 membered heterocycle containing one to three of the same or different heteroatoms selected from the group consisting of O, N and S, optionally containing 1 to 2 carbonyls, wherein the carbon atom of said carbonyl is a member of said 4 to 6 membered heterocycle; (iii) C3-7cycloalkyl; (iv) carbazolyl, fluorenyl, phenyl, —O-phenyl, —O—C1-4alklylene-phenyl, or napthyl; or (v) C1-8alkyl, C2-7alkenyl, —C(O)R3′, CHC(O)O—R3′, CH(CH3)C(O)O—R3′,—C(O)O—R3′or C2-7alkynyl; and wherein R3a is optionally substituted with 1 to 3 of the same or different substituents selected from the group consisting of benzyl, phenyl, —O-phenyl, —O—C1-3alkylenephenyl, —C1-3alkylene-O—C(O)-phenyl, cyano, amino, nitro, halo, C1-6alkyl, C1-3mono-bi-tri-haloalkyl, C1-3mono-bi-tri-haloalkyloxy, (C1-3alkyl)1-2amine, —OR3′, —C(O)R3′, —C(O)O—R3′, —O—C(O)R3′, —N(R3′)2, —C(O)N(R3′)2, —N(R3′)C(O)(R3′)2, —N(R3′)C(O)N(R3′)2, —N(R3′)C(O)OR3′, —O—C(O)N(R3′)2, —N(R3′)SO2R3′, —SO2N(R3′)2 and —SO2R3′; R3′is H or —C1-6alkyl; provided that if R3a is , —C(O)R3′, CHC(O)O—R3′, CH(CH3)C(O)O—R3′or —C(O)O—R3′, then said —C(O)R3′, CHC(O)O—R3′, CH(CH3)C(O)O—R3′or —C(O)O—R3′are unsubstituted; R3b is R3a but is not phenyl, 1-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydro-1-naphthyl, 1H-indol-3-yl, 1-methyl-1H-indol-3-yl, 1-formyl-1H-indol-3-yi, 1 -(1,1-dirnethylethoxycarbonyl)- 1H-indol-3-yl, 4-imidazolyl, 1-methyl-4-imidazolyl, 2-thienyl, 3-thienyl, thiazolyl, 1H-indazol-3-yl, 1-methyl-1H-indazol-3-yl, benzo[b]fur-3-yl, benzo[b]thien-3-yl, pyridinyl, quinolinyl or isoquinolinyl; optionally substituted in the carbon skeleton with mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms or by branched or unbranched alkyl groups, C3-8-cycloalkyl groups, phenylalkyl groups, alkenyl, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycoarbonylalkyl, carboxyalkyl, alkoxycarbonyl, carboxy, dialkylaminoalkyl, dialkylaminoalkoxy, hydroxy, nitro, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, methylsulphonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkanoyl, cyano, tetrazolyl, phenyl, pyridinyl, thiazolyl, furyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl- or trifluoromethylsulphonyl groups; wherein said substituents may be the same or different and the above-mentioned benzoyl, benzoylaznino- and benzoylmnethylamino groups may in turn additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom, or by an alkyl, trifluoromethyl, amino or acetylamino group; D is O, NCN or NSO2C1-3alkyl; A is CH; m and n are each 1; E is N, CE or C; p is 1; G, J and E together form Ax; Ax is a fused heterocycle having two fused rings with 5 to 7 members in each of said rings, said heterocycle containing one to four of the same or different heteroatoms selected from the group consisting of O, N and S; and optionally containing 1 or 2 carbonyls wherein the carbon atom of said carbonyl is a member of said fused heterocycle; and further provided that if Q is Q″, then R3 is R3a; and if Q is Q′, then R3 is R3b. 2. A compound according to claim 1, wherein Q is Q′ and R3 is R3b. 3. A compound according to claim 1, wherein Q is Q″. 4. A compound according to claim 3, wherein Q″ is NH(Sy)SR3. 5. A compound according to claim 3, wherein Q″ is NHC(O)(Sy)SR3. 6. A compound according to claim 3, wherein Q″ is NHC(O)O(Sy)SR3. 7. A compound according to claim 3, wherein Q″ is NHC(O)NH(Sy)SR3. 8. A compound according to claim 3, wherein Q″ is O(Sy)SR3. 9. A compound according to claim 3, wherein Q″ is (Sy)SNHR3. 10. A compound according to claim 3, wherein Q″ is (Sy)SNHC(O)R3. 11. A compound according to claim 3, wherein Q″ is (Sy)SNHC(O)OR3. 12. A compound according to claim 3, wherein Q″ is (Sy)SNHC(O)NHR3. 13. A compound according to claim 3, wherein Q″ is (Sy)SOR3. 14. A compound according to claim 1, wherein V is OR4. 15. A compound according to claim 1, wherein V is —N(R1)(R2). 16. A compound according to claim 1, wherein R4 is H, C1-6alkyl or (C1-4alkylene)0-1R4′and R4′is C3-7cycloalkyl. 17. A compound according to claim 1, wherein V is —N(R1)(R2) and R1 and R2 are each independently L1, wherein L1 is selected from the group consisting of H, C1-6alkyl, —C1-6alkylene-amino(C1-3alkyl)2, C3-7cycloalkyl, phenyl, azetidinyl, adamantyl, tetrahydrofuranyl, furanyl, dioxolanyl, thienyl, tetrahydrothienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, oxazolyl, isoxazolyl, thiazoiyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyranyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, piperidinyl., piperazinyl, morpholino, thiomorpholino and dioxolanyl; or R1 and R2 together with the nitrogen to which they are attached form X, wherein X is azetidinyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, azepinyl, diazepinyl, piperazinyl, piperidinyl, morpholino or thiomorpholino; wherein x is substituted with Y, wherein Y is dioxolanyl, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, phenyl, azetidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, imidazolyl, irnidazolinyl, imidazolidinyl, imidazolidinonyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, azepinyl, diazepinyl, pyridyl, pyrimidinyl, dihydrobenzimidazolonyl, piperazinyl, piperidinyl, morpholino, benzothiazolyl, benzisothiazolyl or thiomorpholino; and wherein X and Y optionally share one carbon atom and together form a spirocyclic moiety. 18. A compound according to claim 1, wherein V is —N(R1)(R2) and R1 and R2 are each independently L1, wherein L1 is selected from the group consisting of H, C1-6alkyl, or R1 and R2 together with the nitrogen to which they are attached form X, wherein X is piperidinyl or morpholino; wherein X is substituted with Y, wherein Y is dioxolanyl, C1-4alkyl or piperidinyl; and wherein X and Y optionally share one carbon atom and together form a spirocydic moiety. 19. A compound according to claim 1, wherein V is —N(R1)(R2) and wherein R1 and R2 are each independently L1, wherein L1 is selected from the group consisting of H, C1-6alkyl. 20. A compound according to claim 1, wherein V is —N(R1)(R2) and wherein R1 and R2 together with the nitrogen to which they are attached form X, wherein X is piperidinyl or morpholino; wherein X is substituted with Y, wherein Y is dioxolanyl, C1-4alkyl or piperidinyl; and wherein X and Y optionally share one carton atom and together form a spirocyclic moiety. 21. A compound according to claim 1, wherein V is —N(R1)(R2) and wherein R1 and R2 together with the nitrogen to which they are attached form X, wherein X is piperidinyl; wherein X is substituted with Y, wherein Y is piperidinyl. 22. A compound according to claim 1, wherein V is —N(R1)(R2) and wherein R1 and R2 together with the nitrogen to which they are attached form X, wherein X is morpholino; wherein X is substituted with Y, wherein Y is C1-4alkyl. 23. A compound according to claim 1, wherein V is —N(R1)(R2) and wherein R1 and R2 together with the nitrogen to which they are attached form X, wherein X is piperidinyl; wherein X is substituted with Y, wherein Y is C1-4alkyl. 24. A conapbund according to claim 1, wherein V is —N(R1)(R2) and wherein R1 and R2 together with the nitrogen to which they are attached form X, wherein X is piperidinyl; wherein X is substituted with Y, wherein Y is dioxolanyl; and wherein X and Y share one carbon atom and together form a spirocyclic moiety. 25. A compound according to claim 1, wherein R3 is R3a and R3a is substituted or unsubstituted phenyl, hydroxyphenyl, azetidinyl, napthyl, C1-6alkyl, C2-6alkenyl, C2-6alkynl, dihydroquinolinonyl, hydroquinolinonyl, quinolinyl, dihydroisoquinolinonyl, hydroisoquinolinonyl, isoquinolinyl, diydroquinazolinonyl, hydroquinazolinonyl, quinazolinyl, dihydroquinoxalinonyl, hydroquinoxalinonyl, quinoxalinyl, benzimidazolyl, indazolyl, dihydrobenzimiidazolonyl, hydrobenzimidazolonyl, benzimidazolinyl, dihydro-benzthiazolonyl, hydrobenztblazolonyl, benzthiazolyl, dihydrobenzoxazolyl, benzotriazolyl, dihydrobeuzotbiophenonyl, hydrobeuzothiophenonyl, beuzothienyl, dihydrobenzofuranonyl, hydrobenzofuranonyl, benzofuranyl, benzdioxolanyl, dihydroindolonyl, hydroindolonyl, indolyl, indolizinyl, isoindolyl, indoliny, indazolyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, furanyl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, purinyl, carbazolyl, pyrimidinyl, piperidinyl, triazolopyrimidinyl, tetrahydropyrazolopyridinyl, piperazinyl or morpholino. 26. A compound according to claim 1, wherein R3 is R3b and R3b is substituted or unsubstituted dihydrobenzimidazolonyl, hydrobenzimidazolonyl, benzimidazolinyl, dihydro-benzthiazolonyl, hydrobenzthiazolonyl, benzthiazolyl, dihydrobenzothiophenonyl, hydrobenzothiophenonyl, dihydrobeuzofuranonyl, hydrobenzofuranonyl, 1H-indazol-5-yl, benzdioxalanyl, dihydrobeuzoxazolyl, benzotriazolyl, dihydroindolonyl, hydroindolonyl, indolizinyl, isoindolyl, indolinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, furanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, purinyl, carbazolyl, pyrimidinyl, piperidinyl, piperazinyl or morpholino. 27. A compound according to claim 1, wherein D is O and m and n are each 1. 28. A compound according to claim 1, wherein p is 1; and G, J and E together fonn Ax. 29. A compound according to claim 1 wherein R3 is R3b and R3b is 1H-Indol-5-yl 1H-Indazol-5-yl 1H-Benzotriazol-5-yl 1,3-Dihydro-indol-2-on-5-yl 3H-Benzooxazol-2-on-6-yl 1,3-Dihydro-benzoimidazol-2-on-5-yl 1-Methyl-1,3-dihydro-benzoimidazol-2-on-6-yl 3,4-Dihydro-1H-quinolin-2-on-6-yl 1,4-Dihydro-benzo[d][1,3]oxazin-2-on-6-yl 3,4-Dihydro-1H-quinazolin-2-on-6-yl 3-Methyl-3,4-dihydro-1H-quinazolin-2-on-6-yl 4H-Benzo[1,4]oxazin-3-on-7-yl wherein Ty is H, C1-4alkyl, F, Cl, Br or nitrile. 30. A compound according to Formula (I) or a pharmaceutically acceptable salt thereof wherein V is —N(R1)(R2); R1 and R2 together with the nitrogen to which they are attached form X, wherein X is piperazinyl; wherein X is substituted with Y, wherein Y is piperidinyl; Q is Q′; wherein Q′is (Sy)SR3; wherein Sy is C1-alkylene and s is 1; U is NH; R3 is R3b wherein R3bis 3H-Benzooxazol-2-on-6-yl wherein Ty is H; D is O; A is CH; m and n are each 1; E is N; p is 1; G, J and E together form Ax; Ax is a fused heterocycle having two fused rings with 6 members in each of said rings, said heterocyole containing two nitrogen atoms; and containing 1 carbonyl wherein the carbon atom of said carbonyl is a member of said fused heterocycle. 31. A compound according to Formula (I) or a pharmaceutically acceptable salt thereof wherein V is —N(R1)(R2); R1 and R2 together with the nitrogen to which they are attached form X, wherein X is piperazinyl; wherein X is substituted with Y, wherein Y is piperidinyl; Q is Q′; wherein Q′ is (Sy)SR3; wherein Sy is C1-alkylene and s is 1; U is NH; R3 is R3b wherein R3b is 1H-Benzotriazol-5-yl wherein Ty is H; D is O; A is CH; m and n are each 1; E is N; p is 1; G, J and E together form Ax; Ax is a fused heterocycle having two fbsed rings with 6 members in each of said rings, said heterocycle containing two nitrogen atoms; and containing 1 carbonyl wherein the carbon atom of said carbonyl is a member of said fused heterocycle. 32. A compound according to Formula (I) or a pharmaceutically acceptable salt thereof wherein V is —N(R1)(R2); R1 and R2 together with the nitrogen to which they are attached form X, wherein X is piperazinyl; wherein X is substituted with Y, wherein Y is piperidinyl; and wherein X and Y are optionally and independently substituted with 1 or 2 of the same or different sub stituents selected from the group consisting of C1-4alkyl; Q is Q′; wherein Q′is (Sy)sR3; wherein Sy is C1-alkylene ands s is 1; U is NH; R3 is R3b wherein R3b is 1H-Indazol-5-yl wherein Ty is C1-4alkyl; D is O; A is CH; m and n are each 1; E is C; p is 1; G, J and E together form Ax; Ax is a fused hetero cycle having two fused rings with 6 members in each of said rings, said heterocycle containing one nitrogen atom; and containing 1 carbonyl wherein the carbon atom of said carbonyl is a member of said fused heterocycle. 33. A compound or a pharmaceutically acceptable salt thereof selected from the group consisting of (±)-3-(1H-Indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(1H-indazol-5 -ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(1H-indol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(1H-indol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid [1-(1H-indol-5 -ylmethyl)-2-(4-isobutyl-piperazin-1-yl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid [2-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-1-(1H-indol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmthyl) -2-(4-isobutyl-piperazin-1-yl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid [2-(1,4-dioxa-8-aza -spiro[4.5]dec-8-yl)-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-(1,4-dioxa-8-aza -spiro[4.5]dec-8-yl)-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-piperidin-1-yl-ethyl]-amide; (±)4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-dimethylcarbamoyl-2-(7-methyl-1H-indazol-5-yl)-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-1-(7-methyl-1H-indazol-5-ylmethyl)-2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-pyrrolidin-1-yl-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-pyridin-4-yl-piperazin-1-yl)-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-pyridin-2-yl-piperazin-1-yl)-ethyl]-amide; 4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid {1-(1-1H-indazol-5-ylmethyl)-2-oxo-2-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-yl]-ethyl}-amide; 4-(3-(1H-Indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid benzyl ester; 4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-oxo-2-piperazin-1-yl-ethyl]-amide; 4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid {1-(1H-indazol-5-ylmethyl)-2-[4-(2-methyl-butyl)-piperazin-1-yl]-2-oxo-ethyl}-amide; 3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid cyclohexyl ester; 3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid 1-benzyl-piperidin-4-yl ester; 3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid 1-methyl-piperidin-4-yl ester, 3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid 4-phenyl-cyclohexyl ester; 3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid (R)-1-pyridin-4-yl-etyl ester; 3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid (S)-1-pyridin-4-yl-ethyl ester; (±)-3-(7-Chloro-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-pipeine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(7-chloro-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-3-(7-Ethyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)piperidine-1-carbonyl]-amino}-propionic acid methyl ester (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(7-ethyl-1H-indazol-5-ylmethyl)-2oxo-ethyl]-amide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(2-methyl-1H-benzoimidazol-5-ylmethyl)-2-oxo-ethyl]-amide; (R)-4(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-2-oxo-1-(2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-ethyl]-amide; (R)-3-(1H-Benzotriazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-(1H-benzotriazol-5-ylmethyl)-2-[1,4′]bipiperidinyl-1′-yl-2-oxo-ethyl]-amide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2[1,4′]bipiperidinyl-1′-yl-2-oxo-1-(2-oxo-2,3-dihydro-1H-indol-5-ylmethyl)-ethyl]-amide; (±)-4(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [1-(4-benzyloxy-2-oxo-2H pyridin-1-ylmethyl)-2-[1,4′]bipiperidinyl-1′-yl-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′bipiperidnyl-1′-yl-1-(4-hydroxy-2-oxo-2H-pyridin-1-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′bipiperidinyl-1′-yl-1-(4-hydroxy-piperidin-1-ylmethyl)-2-oxo-ethy]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-2-oxo-1-(1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-ylmethyl)-ethyl]-amide; (±)-3-(7,7-Dimethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H -quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2[1,4′bipiperidinyl-1′-yl-1-(7,7-dimethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4(2Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2[1,4′]bipiperidinyl-1′-yl-1-(6methoxy-pyridin-3-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1-(2-methoxy-pyrimidin-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [(1-(6-benzyloxy-pyridin-3-ylmethyl)-2-[1,4′bipiperidinyl-1′-yl-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-2-oxo-1-(6-oxo-1,6-dihydro-pyridin-3-ylmethyl)-ethyl]-amide; (±)-2-(7-Methyl-1H-indazol-5-ylmethyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butyric acid methyl ester; (±)-1-[1,4′]Bipiperidinyl-1′-yl-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,4-dihydro-2H -quinazolin-3-yl)-piperidin-1-yl]butane-1,4-dione; (±)-1-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,4-dihydro -2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (±)-N,N-Dimethyl-2-(7-methyl-1H-indazol-5-ylmethyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butyramide; (±)-1-(2,6-Dimethyl-morpholin-4-yl)-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,4-dihydro-2H -quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (±)-2-(7-Methyl-1H-indazol-5-ylmethyl)-1-(4-methyl-piperidin-1-yl)-4-[4-(2-oxo-1,4-dihydro-2H -quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (±)-2-(7-Methyl1H-indazol-5-ylmethyl)-1-morpholin-4-yl-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl) -piperidin-1-yl]-butane-1,4-dione; (±)-2-(7-Methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-1-piperidin-1-yl-butane-1,4-dione; (±)-1-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,4-dihydro-2H -quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (±)-2-(1H-Indazol-5-ylmethyl)-N,N-dimethyl-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl) -piperidine-1-yl]-butyramide; (±)-5-{2-([1,4′]Bipiperidinyl-1′-carbonyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin -1-yl]-butyl}-indazole-1-carboxylic acid tert-butyl ester; (±)-2-(7-Methyl-1H-indazol-5-ylmethyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1yl]-N-prop-2-ynyl-butyramide; (L)-{1-([1,4′]Bipiperidinyl-1′-carbonyl)-3-oxo-3-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-(1H-indol-5-ylamino)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl) -piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-(5-chloro-2-nitro-phenylamino)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin -3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′Bipiperidinyl-1′-yl-2-(6-chloro-pyrimidin-4-ylamino)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin -3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-(2-chloro-9H-purin-6-ylamino)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin -3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-2-(4-Amino-6-methyl-5-nitro-pyrimidin-2-ylamino)-1-[1,4′]bipiperidinyl-1′-yl-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-(4,5-diamino-6-methyl-pyrimidin-2-ylamino)-4-[4-(2-oxo-1,4-dihydro -2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-(7-methyl-1H-[1,2,3]triazo[4,5-d]pyrimidin-5-ylamino)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-((2′-pyridyl)-methyl-amino)-4-]4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-((5′-indazolyl)-methyl-amino)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-((3′-methyl-phenyll)-methyl-amino)-4-[4-(2-oxo-1,4-dihydro-2H -quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-2-(pyrimidin -4-ylamino)-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-(4-hydroxy-cyclohexylamino-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (L)-1-[1,4′]Bipiperidinyl-1′-yl-2-[(1H-imidazol-4-ylmethyl)-amino]-4-[4-(2-oxo-1,4-dihydro-2H -quinazolin-3-yl)piperidin-1-yl]-butane-1,4-dione; (L)-N-{1-([1,4′]Bipiperidinyl-1′-carbonyl)-3-oxo-3-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-propyl}-4-hydroxy-benzamide; (L)-N-{1-([1,4′]Bipiperidinyl-1′-carbonyl)-3-oxo-3-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-propyl}-4-hydroxy-benzamide; (L)-1H-Pyrazole-3-carboxylic acid{1-([1,4′]bipiperidinyl-1′-carbonyl)-3-oxo-3-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-propyl}-amide; (±)-1-[1,4′]Bipiperidinyl-1′-yl-2-(1H-indazol-5-ylamino)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (±)-3-(3-Cyano-1H-indol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-carbonyl]-amino}-propionic acid methyl ester; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl -1-(3-cyano-1H-indol-5-yl-methyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1(3-cyano-7-methyl-1H-indol-5-yl-methyl)-2-oxo-ethyl]-amide; (±)-3-(7-Isopropyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dibydro-2H-quinazolin-3-yl)-piperidin-1-carbonyl]-amino}-propionic acid methyl ester; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1(7-isopropyl-1H-indazol-5-yl-methyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1(7-ethyl-1H-indazol-5-yl-methyl)-2-oxo-ethyl]-amide; (±)-4-(2,2-Dioxo-1,4-dihydro-2H-2λ6-benzo[1,2,6]thiadiazin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-1(7-methyl-1H-indazol-5-yl-methyl)-2-oxo-ethyl]-amide; (±)-4-(2,2-Dioxo-1,4-dihydro-2H-2λ6-benzo[1,2,6]thiadiazin-3-yl)-piperidin-1-carboxylic acid [2-[1,4′bipiperidinyl-1′-yl-1(7-ethyl-3-methyl-1H-indazol-5-yl-methyl)-2-oxo-ethyl]-amide; (±)-2-[4-(6-Cyano-2-oxo-1,4-dihydro-2H-qinazolin-3-yl)piperidine-1-carbonyl]-amino]-3-(7-methyl-1H-indazol-5-yl)-propionic acid methyl ester; (±)-4-(6-Cyano-2-oxo-1,4-dihydro-2H-qinazolin-3-yl)-piperidine-1-carboxylic acid{2-[1,4′bipiperidinyl-1′-yl-1-(7-methyl-1H-indazol-5-yl methyl)-2-oxo-ethyl}-amide; (±)-4-(2-Oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl-1-carboxylic acid{2-[1,4′]bipiperidinyl-1′-yl-1-(7-methyl-1H-indazol-5-yl methyl)-2-oxo-ethyl}-amide; (±)-4-(6-Hydroxy-2-oxo-1,4-dihydro-2H-qinazolin-3-yl)-piperidine-1-carboxylic acid{2-[1,4′]bipiperidinyl-1′-yl-1-(7-methyl-1H-indazol-5-yl methyl)-2-oxo-ethyl}-amide; (±)-4-(8-Methoxy-2-oxo-1,4-dihydro-2H-qinazolin-3-yl)-piperidine-1-carboxylic acid{2-[1,4′]bipiperidinyl-1′-yl-1-(7-methyl-1H-indazol-5-yl methyl)-2-oxo-ethyl}-amide; (±)-4(8-Chloro-2-oxo-1,4-dihydro-2H-qinazolin-3-yl)-piperidine-1-carboxylic acid{2-[1,4′]bipiperidinyl-1′-yl-1-(7-methyl-1H-indazol-5-yl methyl)-2-oxo-ethyl}-amide; (±)-N-(3-(7-Ethyl-1H-indazol-5-yl)-1-(6,7-dihydro-1H-pyrazolo[4,3-c]pyridin-5(4H)-yl)-1-oxopropan-2-yl)-4-(1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide; (±)-Methyl 2-(4-(8-fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide)-3-(7-methyl-1H-indazol-5-yl)propanoate; (±)-4-(8-Fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide; (±)4-(8-Fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl)piperidine-1-carboxamide; (±)-4-(8-Fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)-N-(1-(4-(4-fluorophenyl)piperazin-1-yl)-3-(7-methy-1H-indazol-5-yl)-1-oxopropan-2-yl)piperidine-1-carboxamide; (±)-4-(8-Fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)-N-(1-(4-(2-fluorophenyl)piperazin-1-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl)piperidine-1-carboxamide; (±)-4-(8-Fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-o-tolylpiperazin-1-yl)propan-2-yl)piperidine-1-carboxamide; (±)-Methyl 2-(4-(8-fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide)-3-(7-ethyl -3-methyl-1H-indazol-5-yl)propanoate; (±)-N-(3-(7-Ethyl-3-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)-4-(8-fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide; (R)-N-((R)-3-(2-Oxo-2,3-dihydro-benzooxazol-6-yl)-1-oxo-1-(4-(piperidin-1-yl)propan-2-yl)-4-(8-fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide; (±)-4-(8-Fluoro-1,2-dihydro-2,4-dioxoquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide; N-((R)-3-(2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)-4-(1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide; N-((R)-1-(dimethylcarbamoyl)-2-(2-trifluoromethyl)-1H-benzo[d]imidazol-5-yl)ethyl)-4-(1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide; (R)-methyl 2-(4-(1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-6-yl)propanoate; N-((R)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-6-yl)-1-oxo-1(4-piperidine-1-yl)propan-2-yl)-4-(1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamide; N-((R)-1-(dimnethylcarbamoyl)-2-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-6-yl)ethyl)-4-(1,2-dihydro-2-oxoquinazolin-3(4H))-yl)piperidine-1-carboxamide; 4-(1,2-dihydro-2,4-dioxoquinazolin-3-(4H)-yl)-N-((R)-3-(7-methyl-1H-benzo[d][1,2,3]triazol-5-yl-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid[2-(4-cyclohexyl-piperazin-1-yl)-2-oxo-1-(2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-ethyl]-amide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid[2-(4-isopropyl-piperazin-1-yl)-2-oxo-1-(2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-ethyl]-amide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid[2-[1,4′]bipiperidinyl-1′-yl-1-(4-chloro-2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-2-oxo-ethyl]-amide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid[2-[1,4′]bipiperidinyl-1′-yl-1-(5-chloro-2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-2-oxo-ethyl]-amide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid[2-[1,4′]bipiperidinyl-1′-yl-1-(4-bromo-2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-2-oxo-ethyl]-amide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid[2-[1,4′]bipiperidinyl-1′-yl-1-(5-bromo-2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-2-oxo-ethyl]-amide; (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid[2-[1,4′]bipiperidinyl-1′-yl-1-(4-iodo-2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-2-oxo-ethyl]-amide; (±)-N-(1-Benzyl-2-hydroxy-ethyl)-2-(7-methyl-1H-indazol-5-ylmethyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butyramide; (4Phenyl-acetic acid N′-{2-(7-methyl-1H-indazol-5-ylmethyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro 2H -quinazolin-3-yl)-piperidin-1-yl)-butyryl}-hydrazide; (±)-1-[1,4′]Bipiperidinyl-1′-yl-4-[4-(8-fluoro-2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-2-(7-methyl-1H-indazol-5-ylmethyl)-butane-1,4-dione; (±)1-(4-Cyclohexyl-piperazin-1-yl)-2-(2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butane-1,4-dione; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)piperidine-1-carboxylic acid[2-(4-cyclohexyl -piperazin-1-yl)-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid[2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino)}-propionic acid tert-butyl ester; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-}[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid 1-methyl cyclohexyl ester; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl}-amino}-propionic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid piperidin-4-yl ester; (±)-4-(3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl[-amino}-propionyloxy)-piperidine-1-carboxylic acid tert-butyl ester, (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid 3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-yl ester, (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino)-propionic acid 1-diethylamino-1-methyl-ethyl ester; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid 1,1-dimethyl-2-phenyl-ethyl ester; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino)-propionic acid 1,1-dimethyl-3-phenyl-propyl ester; (±)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid ethyl ester; and (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1d-carboxylic acid[2-[1,4′]bipiperidinyl-1′-yl-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]amide. 34. (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4′]bipiperidinyl-1′-yl-2-oxo-1-(2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-ethyl]-amide or a pharmaceutically acceptable salt thereof. 35. (R)-3-(1H-Benzotriazol-5-yl-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester or a pharrvaoeixtiaally acceptable salt thereof. 36. A pharmaceutical composition comprising a compound according claim 1 or any one of claims 30–35.