Claims for Patent: 7,741,356

Summary for Patent: 7,741,356

Title:	Compounds as opioid receptor modulators
Abstract:	The present invention is directed to novel opioid receptor modulators of Formula (I). The invention further relates to methods for preparing such compounds, pharmaceutical compositions containing them, and their use in the treatment of disorders that may be ameliorated or treated by the modulation of opioid receptors.
Inventor(s):	Henry J. Breslin, Chaozhong Cai, Wei He, Robert W. Kavash
Assignee:	Janssen Pharmaceutica NV
Application Number:	US11/079,647
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,741,356
Patent Claims:	1. A compound of Formula (I) wherein: R1 is selected from the group consisting of hydrogen, C1-6alkyl, cycloalkyl, heterocyclyl, aryl(C1-6)alkyl, and heteroaryl(C1-6)alkyl; wherein when R1 is phenyl(C1-6)alkyl, phenyl is optionally fused to a heterocyclyl or cycloalkyl; wherein when R1 is C1-2alkyl, said C1-2alkyl is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkoxy, aryl, cycloalkyl, heterocyclyl, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, and carboxy; and further, wherein when R1 is C3-6alkyl, said C3-6alkyl is optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkoxy, aryl, cycloalkyl, heterocyclyl, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, and carboxy; wherein the cycloalkyl and heterocyclyl of C1-2alkyl and C3-6alkyl are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, carboxy, aryl(C1-6)alkoxycarbonyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, and aminosulfonyl; furthermore, wherein the cycloalkyl and heterocyclyl of R1 are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, carboxy, aryl(C1-6)alkoxycarbonyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, and aminosulfonyl; furthermore, wherein the aryl and heteroaryl portion of the R1 substituents aryl(C1-6)alkyl and heteroaryl(C1-6)alkyl, are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-6alkyl; hydroxy(C1-6)alkyl; C1-6alkoxy; C6-10aryl(C1-6)alkyl; C6-10aryl(C1-6) alkoxy; C6-10aryl; heteroaryl optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy; cycloalkyl; heterocyclyl; C6-10aryloxy; heteroaryloxy; cycloalkyloxy; heterocyclyloxy; amino; C1-6alkylamino; (C1-6alkyl)2amino; C3-6cycloalkylaminocarbonyl; hydroxy(C1-6) alkylaminocarbonyl; C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; heterocyclylcarbonyl; carboxy; C1-6alkoxycarbonyl; C1-6alkoxycarbonyloxy; C1-6alkylcarbonyl; C1-6alkylcarbonylamino; aminocarbonyl; C1-6alkylaminocarbonyl; (C1-6alkyl)2aminocarbonyl; cyano; halogen; trifluoromethyl; trifluoromethoxy; and hydroxy; provided that no more than one R11 substituent is selected from the group consisting of C6-10aryl(C1-6)alkyl; C6-10aryl(C1-6)alkoxy; C6-10aryl; heteroaryl optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy; cycloalkyl; heterocyclyl; C6-10aryloxy; heteroaryloxy; cycloalkyloxy; C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; heterocyclylcarbonyl, and heterocyclyloxy; R2 is hydrogen, C1-8alkyl, hydroxy(C1-8)alkyl, C6-10aryl(C1-6)alkoxy(C1-6)alkyl, or C6-10aryl(C1-8)alkyl; wherein the C6-10aryl group in the C6-10aryl-containing substituents of R2 are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, hydroxy, amino, C1-6alkylamino, (C1-6alkyl)2amino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, cyano, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy; and, wherein the C1-6alkyl and C1-6alkoxy substituents of aryl are optionally substituted with hydroxy, amino, C1-6alkylamino, (C1-6alkyl)2amino, or aryl; A is a-1, optionally substituted with R3 and R5; wherein A-B is N—C; R3 is one to two substituents independently selected from the group consisting of C1-6alkyl, aryl, aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, heteroaryl, heteroaryl(C1-6)alkyl, heteroaryl(C2-6)alkenyl, heteroaryl(C2-6)alkynyl, amino, C1-6alkylamino, (C1-6alkyl)2amino, arylamino, heteroarylamino, aryloxy, heteroaryloxy, trifluoromethyl, and halogen; wherein the aryl, heteroaryl, and the aryl and heteroaryl of aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, heteroaryl(C1-6)alkyl, heteroaryl(C2-6)alkenyl, heteroaryl(C2-6)alkynyl, arylamino, heteroarylamino, aryloxy, and heteroaryloxy, are optionally substituted with one to five fluoro substituents or one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, C6-10aryl(C1-6)alkyl, C6-10aryl(C1-6)alkoxy, C6-10aryl, C6-10aryloxy, heteroaryl(C1-6)alkyl, heteroaryl(C1-6)alkoxy, heteroaryl, heteroaryloxy, C6-10arylamino, heteroarylamino, amino, C1-6alkylamino, (C1-6alkyl)2amino, carboxy(C1-6)alkylamino, carboxy, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, C1-6alkylcarbonylamino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, carboxy(C1-6)alkylaminocarbonyl, cyano, halogen, trifluoromethyl, trifluoromethoxy, hydroxy, C1-6alkylsulfonyl, and C1-6alkylsulfonylamino; provided that no more than one such substituent on the aryl or heteroaryl portion of R3 is selected from the group consisting of C6-10aryl(C1-6)alkyl, C6-10aryl(C1-6)alkoxy, C6-10aryl, C6-10aryloxy, heteroaryl(C1-6)alkyl, heteroaryl(C1-6)alkoxy, heteroaryl, heteroaryloxy, C6-10arylamino, heteroarylamino; and wherein C1-6alkyl and C1-6alkyl of aryl(C1-6)alkyl and heteroaryl(C1-6)alkyl are optionally substituted with a substituent selected from the group consisting of hydroxy, carboxy, C1-4alkoxycarbonyl, amino, C1-6alkylamino, (C1-6alkyl)2amino, aminocarbonyl, (C1-4)alkylaminocarbonyl, di(C1-4)alkylaminocarbonyl, aryl, heteroaryl, arylamino, heteroarylamino, aryloxy, heteroaryloxy, aryl(C1-4)alkoxy, and heteroaryl(C1-4)alkoxy; R4 is C6-10aryl or a heteroaryl selected from the group consisting of furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolinyl, benzofuryl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolizinyl, quinolinyl, isoquinolinyl and quinazolinyl; wherein R4 is optionally substituted with one to three R41 substituents independently selected from the group consisting of (C1-6)alkyl optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino; (C1-6)alkoxy; phenyl(C1-6)alkoxy; phenyl(C1-6)alkylcarbonyloxy wherein C1-6 alkyl is optionally substituted with amino; a non fused 5-membered-heteroaryl(C1-6)alkylcarbonyloxy; a non fused 5-membered-heteroaryl; hydroxy; halogen; aminosulfonyl; formylamino; aminocarbonyl; C1-6alkylaminocarbonyl wherein (C1-6)alkyl is optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino; (C1-6alkyl)2aminocarbonyl wherein each (C1-6)alkyl is optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino; heterocyclylcarbonyl wherein heterocyclyl is a 5-7 membered nitrogen-containing ring and said heterocyclyl is attached to the carbonyl carbon via a nitrogen atom; carboxy; or cyano; and wherein the phenyl portion of phenyl(C1-6)alkylcarbonyloxy is optionally substituted with (C1-6)alkyl (C1-6) alkoxy, halogen, cyano, amino, or hydroxy; provided that no more than one R41 is C1-6alkyl substituted with C1-6alkylamino or (C1-6alkyl)2amino; aminosulfonyl; formylamino; aminocarbonyl; C1-6alkylaminocarbonyl; (C1-6alkyl)2aminocarbonyl; heterocyclylcarbonyl; hydroxy; carboxy; or a phenyl- or heteroaryl-containing substituent; R5 is a substituent on a nitrogen atom of ring A selected from the group consisting of hydrogen and C1-4alkyl; R6 is hydrogen or C1-6alkyl; R7 is hydrogen or C1-6alkyl; Ra and Rb are independently selected from the group consisting of hydrogen, C1-6alkyl, and C1-6alkoxycarbonyl; alternatively, when Ra and Rb are each other than hydrogen, Ra and Rb are optionally taken together with the nitrogen atom to which they are both attached to form a five to eight membered monocyclic ring; L is O; and pharmaceutically acceptable enantiomers, diastereomers, racemates, and salts thereof. 2. The compounds of claim 1 wherein R1 is selected from the group consisting of hydrogen, C1-6alkyl, aryl(C1-4)alkyl, and heteroaryl(C1-4)alkyl; wherein the aryl and heteroaryl portion of aryl(C1-4)alkyl and heteroaryl(C1-4) alkyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-6alkoxy; heteroaryl optionally substituted with one to two substitutents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy; carboxy; C1-4alkoxycarbonyl; C1-4alkoxycarbonyloxy; aminocarbonyl; C1-4alkylaminocarbonyl; C3-6cycloalkylaminocarbonyl; hydroxy(C1-6) alkylaminocarbonyl; C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; heterocyclylcarbonyl; cyano; halogen; trifluoromethoxy; and hydroxy; provided that no more than one R11 is heteroaryl (optionally substituted with one to two C1-4alkyl substituents); C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; or heterocyclylcarbonyl. 3. The compounds of claim 1 wherein R1 is selected from the group consisting of C6-10aryl(C1-4)alkyl, pyridinyl(C1-4)alkyl, and furanyl(C1-4)alkyl; wherein C6-10aryl, pyridinyl, and furanyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-3alkoxy; tetrazolyl; carboxy; C1-4alkoxycarbonyl; aminocarbonyl; C1-4alkylaminocarbonyl; C1-3alkylaminocarbonyl; C3-6cycloalkylaminocarbonyl; hydroxy(C1-4)alkylaminocarbonyl; C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; morpholin-4-ylcarbonyl; cyano; halogen; and trifluoromethoxyl; provided that no more than one R11 is C6-10arylaminocarbonyl. 4. The compounds of claim 1 wherein R1 is selected from the group consisting of phenyl(C1-3)alkyl, pyridinyl(C1-3)alkyl, and furanyl(C1-3)alkyl; wherein phenyl, pyridinyl, and furanyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-3alkoxy; tetrazolyl, C3-6cycloalkylaminocarbonyl; hydroxy(C1-4) alkylaminocarbonyl; C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; morpholin-4-ylcarbonyl; chloro; fluoro; trifluoromethoxy; C1-4alkoxycarbonyl; and carboxy; provided that no more than one R11 is C6-10arylaminocarbonyl. 5. The compounds of claim 1 wherein R1 is phenylmethyl, pyridinylmethyl, or furanylmethyl; wherein phenyl, pyridinyl, and furanyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of methoxy; tetrazolyl; cyclopropylaminocarbonyl, (2-hydroxyeth-1-yl)aminocarbonyl; methoxycarbonyl; phenylaminocarbonyl wherein phenyl is optionally substituted with carboxy; morpholin-4-ylcarbonyl; and carboxy. 6. The compounds of claim 1 wherein R2 is a substituent selected from the group consisting of hydrogen, C1-4alkyl, hydroxy(C1-4)alkyl, and phenyl(C1-6) alkoxy(C1-4)alkyl; wherein said phenyl is optionally substituted with one to two substituents independently selected from the group consisting of C1-3alkyl, C1-3alkoxy, hydroxy, cyano, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy. 7. The compounds of claim 1 wherein R2 is a substituent selected from the group consisting of hydrogen and C1-4alkyl. 8. The compounds of claim 1 wherein R2 is hydrogen or methyl. 9. The compounds of claim 1 wherein R3 is one to two substituents independently selected from the group consisting of C1-6alkyl, halogen, and aryl; wherein aryl is optionally substituted with one to three substituents independently selected from the group consisting of halogen, carboxy, aminocarbonyl, C1-3alkylsulfonylamino, cyano, hydroxy, amino, C1-3alkylamino, and (C1-3alkyl)2amino. 10. The compounds of claim 1 wherein R3 is one to two substituents independently selected from the group consisting of C1-3alkyl, bromo, and phenyl; wherein phenyl is optionally substituted with one to three substituents independently selected from the group consisting of chloro, fluoro, iodo, carboxy, aminocarbonyl, and cyano. 11. The compounds of claim 1 wherein R3 is one to two substituents independently selected from the group consisting of methyl and phenyl; wherein phenyl is optionally substituted with one to three substituents independently selected from the group consisting of chloro and carboxy. 12. The compounds of claim 1 wherein at least one R3 substituent is phenyl. 13. The compounds of claim 1 wherein R3 is a substituent selected from the group consisting of methyl and phenyl; wherein phenyl is optionally substituted with one to two substituents independently selected from the group consisting of chloro and carboxy. 14. The compounds of claim 1 wherein R4 is C6-10aryl optionally substituted with one to three R41 substituents independently selected from the groupconsisting of (C1-3)alkyl, (C1-6)alkoxy, phenyl(C1-6)alkoxy; hydroxy; halogen; formylamino; aminocarbonyl; C1-6alkylaminocarbonyl; (C1-6alkyl)2aminocarbonyl; heterocyclylcarbonyl wherein heterocyclyl is a 5-7 membered nitrogen-containing ring and said heterocyclyl is attached to the carbonyl carbon via a nitrogen atom; carboxy; and cyano; provided that no more than one R41 substituent is formylamino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, heterocyclylcarbonyl, hydroxy, carboxy, or a phenyl-containing substituent. 15. The compounds of claim 1 wherein R4 is phenyl substituted with one to three R41 substituents independently selected from the group consisting of (C1-3)alkyl, (C1-3)alkoxy, phenyl(C1-3)alkoxy, hydroxy, C1-6alkylaminocarbonyl, and aminocarbonyl; provided that no more than one R41 substituent is aminocarbonyl, C1-6alkylaminocarbonyl, hydroxy, or a phenyl-containing substituent. 16. The compounds of claim 1 wherein R4 is phenyl substituted at the 4-position with hydroxy, C1-3alkylaminocarbonyl, or aminocarbonyl, and optionally substituted with one to two substituents independently selected from the group consisting of methyl, methoxy, and benzyloxy. 17. The compounds of claim 1 wherein R4 is phenyl substituted at the 4-position with hydroxy, C1-3alkylaminocarbonyl, or aminocarbonyl, and optionally substituted with one to two methyl substituents. 18. The compounds of claim 1 wherein R4 is phenyl substituted at the 4-position with hydroxy, C1-3alkylaminocarbonyl, or aminocarbonyl, and substituted at the 2- and 6-positions with methyl substituents. 19. The compounds of claim 1 wherein R5 is hydrogen or methyl. 20. The compounds of claim 1 wherein R5 is hydrogen. 21. The compounds of claim 1 wherein R6 is hydrogen or methyl. 22. The compounds of claim 1 wherein R6 is hydrogen. 23. The compounds of claim 1 wherein R7 is hydrogen or methyl. 24. The compounds of claim 1 wherein R7 is hydrogen. 25. The compounds of claim 1 wherein Ra and Rb are independently selected from the group consisting of hydrogen and C1-3alkyl; or, when Ra and Rb are each other than hydrogen, Ra and Rb are optionally taken together with the nitrogen atom to which they are both attached to form a five to seven membered monocyclic ring. 26. The compounds of claim 1 wherein Ra and Rb are independently hydrogen or methyl. 27. The compounds of claim 1 wherein Ra and Rb are each hydrogen. 28. The compounds of claim 1 that are present in their RR, SS, RS, and SR configurations. 29. The compounds of claim 1 in their S,S configuration. 30. A compound of Formula (Ia): wherein: R1 is selected from the group consisting of hydrogen, C1-6alkyl, aryl(C1-4)alkyl, and heteroaryl(C1-4)alkyl; wherein the aryl and heteroaryl portion of aryl(C1-4)alkyl and heteroaryl(C1-4) alkyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-6alkoxy; heteroaryl optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy; carboxy; C1-4alkoxycarbonyl; C1-4alkoxycarbonyloxy; aminocarbonyl; C1-4alkylaminocarbonyl; C3-6cycloalkylaminocarbonyl; hydroxy(C1-6) alkylaminocarbonyl; C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; heterocyclylcarbonyl; cyano; halogen; trifluoromethoxy; and hydroxy; provided that no more than one R11 is heteroaryl (optionally substituted with one to two C1-4alkyl substituents); C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; or heterocyclylcarbonyl; R2 is selected from the group consisting of hydrogen, C1-4alkyl, hydroxy(C1-4) alkyl, and phenyl(C1-6)alkoxy(C1-4)alkyl; wherein said phenyl is optionally substituted with one to two substituents independently selected from the group consisting of C1-3alkyl, C1-3alkoxy, hydroxy, cyano, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy; R3 is one to two substituents independently selected from the group consisting of C1-6alkyl, halogen, and aryl; wherein aryl is optionally substituted with one to three substituents independently selected from the group consisting of halogen, carboxy, aminocarbonyl, C1-3alkylsulfonylamino, cyano, hydroxy, amino, C1-3alkylamino, and (C1-3alkyl)2amino; R4 is C6-10aryl optionally substituted with one to three R41 substituents independently selected from the group consisting of (C1-3)alkyl, (C1-6) alkoxy, phenyl(C1-6)alkoxy; hydroxy; halogen; formylamino; aminocarbonyl; C1-6alkylaminocarbonyl; (C1-6alkyl)2aminocarbonyl; heterocyclylcarbonyl wherein heterocyclyl is a 5-7 membered nitrogen-containing ring and said heterocyclyl is attached to the carbonyl carbon via a nitrogen atom; carboxy; and cyano; provided that no more than one R41 substituent is formylamino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, heterocyclylcarbonyl, hydroxy, carboxy, or a phenyl-containing substituent. R5 is hydrogen or methyl; Ra and Rb are independently hydrogen or C1-3alkyl; or, when Ra and Rb are each other than hydrogen, Ra and Rb are optionally taken together with the nitrogen atom to which they are both attached to form a five to seven membered monocyclic ring; and pharmaceutically acceptable enantiomers, diastereomers, racemates, and salts thereof. 31. A compound of Formula (Ia) wherein: R1 is selected from the group consisting of C6-10aryl(C1-4)alkyl, pyridinyl(C1-4) alkyl, and furanyl(C1-4)alkyl; wherein C6-10aryl, pyridinyl, and furanyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-3alkoxy; tetrazolyl; carboxy; C1-3alkoxycarbonyl; aminocarbonyl; C1-4alkylaminocarbonyl; C1-3alkylaminocarbonyl; C3-6cycloalkylaminocarbonyl; hydroxy(C1-4) alkylaminocarbonyl; C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; morpholin-4-ylcarbonyl; cyano; halogen; trifluoromethoxy; C1-4alkoxycarbonyl; or carboxy; provided that no more than one R11 is C6-10arylaminocarbonyl; R2 is hydrogen or C1-4alkyl; R3 is one to two substituents independently selected from the group consisting of C1-3alkyl, bromo, and phenyl; wherein phenyl is optionally substituted with one to three substituents independently selected from the group consisting of chloro, fluoro, carboxy, aminocarbonyl, and cyano; R4 is phenyl substituted with one to three substituents independently selected from the group consisting of (C1-3)alkyl, (C1-3)alkoxy, phenyl(C1-3)alkoxy, hydroxy, C1-6alkylaminocarbonyl, and aminocarbonyl; provided that no more than one R41 substituent is aminocarbonyl, C1-6alkylaminocarbonyl, hydroxy, or a phenyl-containing substituent; R5 is hydrogen; Ra and Rb are independently hydrogen or methyl; and pharmaceutically acceptable enantiomers, diastereomers, racemates, and salts thereof. 32. A compound of Formula (Ia) wherein: R1 is selected from the group consisting of phenyl(C1-3)alkyl, pyridinyl(C1-3) alkyl, and furanyl(C1-3)alkyl; wherein phenyl, pyridinyl, and furanyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of is C1-3alkoxy; tetrazolyl, C3-6cycloalkylaminocarbonyl; hydroxy(C1-4)alkylaminocarbonyl; C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl; morpholin-4-ylcarbonyl; chloro; fluoro; trifluoromethoxy; methoxycarbonyl; and carboxy; provided that no more than one R11 is C6-10arylaminocarbonyl; R2 is hydrogen or methyl; R3 is one to two substituents independently selected from the group consisting of methyl and phenyl; wherein phenyl is optionally substituted with one to three substituents independently selected from the group consisting of chloro and carboxy; R4 is phenyl substituted at the 4-position with hydroxy, C1-3alkylaminocarbonyl, or aminocarbonyl, and optionally substituted with one to two substituents independently selected from the group consisting of methyl, methoxy, and benzyloxy; R5 is hydrogen; Ra and Rb are each hydrogen; and pharmaceutically acceptable enantiomers, diastereomers, racemates, and salts thereof. 33. A compound according to claim 32 wherein R1 is phenylmethyl, pyridinylmethyl, or furanylmethyl; wherein phenyl, pyridinyl, and furanyl are optionally substituted with one to three R11 substituents independently selected from is the group consisting of methoxy, tetrazolyl, cyclopropylaminocarbonyl, (2-hydroxyeth-1-yl)aminocarbonyl, phenylaminocarbonyl wherein phenyl is optionally substituted with carboxy, morpholin-4-ylcarbonyl, methoxycarbonyl, and carboxy; provided that no more than one R11 is phenylaminocarbonyl. 34. A compound according to claim 32 wherein R4 is phenyl substituted at the 4-position with hydroxy, C1-3alkylaminocarbonyl, or aminocarbonyl, and optionally substituted with one to two methyl substituents. 35. A compound according to claim 32 wherein R4 is phenyl substituted at the 4-position with hydroxy, C1-3alkylaminocarbonyl, or aminocarbonyl, and substituted at the 2- and 6-positions with methyl substituents. 36. A compound of Formula (Ib) Formula (Ib) wherein L is O and R1, R2, R3-1, R3-2, R5, Ra, Rb, and R41 are dependently selected from the group consisting of: R1 R2 R3-1 R3-2 R5 R41 Ra/Rb 2- methyl phenyl H H 2,6-dimethyl-4- H Aminocarbonyl- aminocarbonyl phenylmethyl 2-Cyano-phenyl methyl phenyl H H 2,6-dimethyl-4- H methyl aminocarbonyl 2-Bromo-phenyl methyl phenyl H H 2,6-dimethyl-4- H methyl aminocarbonyl 3-Carboxy-4- methyl phenyl H H 4-aminocarbonyl H methoxy-phenyl methyl 3-Carboxy-4- H phenyl H H 4-aminocarbonyl H methoxy-phenyl methyl 3-Carboxy-4- H phenyl H H 2,6-dimethyl-4- H methoxy-phenyl aminocarbonyl methyl 3- H phenyl H H 2,6-dimethyl-4- H Methoxycarbonyl- aminocarbonyl 4-methoxy- phenylmethyl 3-(1H-tetrazol-5- methyl phenyl H H 2,6-dimethyl-4- H yl)-4-methoxy- phenylmethyl 3- methyl phenyl H H 2,6-dimethyl-4- H Methoxycarbonyl- aminocarbonyl phenylmethyl 3-Methoxy methyl naphthalen- H H 2,6-dimethyl-4- H carbonyl- 1-yl aminocarbonyl phenylmethyl 3-Carboxy- methyl naphthalen- H H 2,6-dimethyl-4- H phenylmethyl 1-yl 3-Carboxy- methyl 4-chloro- Me H 2 ,6-dimethyl-4- H phenylmethyl phenyl 4-Carboxy- methyl naphthalen- H H 2,6-dimethyl-4- H phenylmethyl 1-yl 3-Methoxy-4- methyl phenyl H H 2,6-dimethyl-4- H carboxy- aminocarbonyl phenylmethyl 3,4-Dihydroxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy Piperidin-4- methyl phenyl H H 2,6-dimethyl-4- H ylmethyl hydroxy 3-Methoxy methyl phenyl H H 2,6-dimethyl-4- H carbonyl-4- aminocarbonyl methoxy-phenyl methyl 3-Carboxy-4- methyl phenyl H H 2,6-dimethyl-4- H methoxy- aminocarbonyl phenylmethyl 3,4-Dimethoxy- methyl 3-bromo H H 2,6-dimethyl-4- H phenylmethyl phenyl aminocarbonyl 3,4-Dimethoxy- methyl 3-carboxy H H 2,6-dimethyl-4- H phenylmethyl phenyl aminocarbonyl 3,4-Dimethoxy- benzyl phenyl H H 2,6-dimethyl-4- H phenylmethyl oxy hydroxy methyl 3,4-Dimethoxy- methyl 3-amino H H 2,6-dimethyl-4- H phenylmethyl carbonyl aminocarbonyl phenyl 3,4-Dimethoxy- methyl 3-cyano H H 2,6-dimethyl-4- H phenylmethyl phenyl aminocarbonyl Isopropyl H quinoxalin- Me H 2,6-dimethyl-4- H 8-yl hydroxy 3,4-Dimethoxy- methyl 2-bromo H H 2,6-dimethyl-4- H phenylmethyl phenyl aminocarbonyl 3,4-Dimethoxy- methyl 2-cyano H H 2,6-dimethyl-4- H phenylmethyl phenyl aminocarbonyl 3,4-Dimethoxy- methyl 2-amino 2,6-dimethyl-4- H phenylmethyl carbonyl aminocarbonyl phenyl 3,4-Dimethoxy- methyl 2-carboxy H H 2,6-dimethyl-4- H phenylmethyl phenyl aminocarbonyl 3,4-Dibenzyloxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy [1,3]benzo methyl phenyl H H 2,6-dimethyl, 4- H dioxal-5-yl hydroxy 4-Methoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 3-Methoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 2,4-Dimethoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 3,4-Dimethoxy- H phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy Isopropyl H 4-methyl H H 2,6-dimethyl-4- H carbonyl hydroxy phenyl Isopropyl H 3-fluoro, 4- Me H 2,6-dimethyl-4- H carboxy- hydroxy phenyl Isopropyl H 2-phenyl- Me H 2,6-dimethyl-4- H ethyl hydroxy en-1-yl Isopropyl H 4-hydroxy Me H 2,6-dimethyl-4- H methyl hydroxy phenyl Benzhydryl H phenyl H H 2,6-dimethyl-4- H hydroxy Isopropyl H 4-cyano Me H 2,6-dimethyl-4- H phenyl hydroxy Benzyl methyl 4-trifluoro H H 2,6-dimethyl-4- H methyl aminocarbonyl phenyl Isopropyl H 3-trifluoro Me H 2,6-dimethyl-4- H methoxy hydroxy phenyl Isopropyl H 4-trifluoro Me H 2,6-dimethyl-4- H methoxy hydroxy phenyl Isopropyl H 3-methane Me H 2,6-dimethyl-4- H sulfonyl hydroxy amino phenyl Isopropyl H 4-(2- Me H 2,6-dimethyl-4- H carboxy hydroxy ethyl) phenyl Isopropyl H 3-amino-5- Me H 2,6-dimethyl-4- H carboxy hydroxy phenyl 3-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 4-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl carboxy 4-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl aminocarbonyl 4-Methoxy methyl phenyl H H 2,6-dimethyl-4- H carbonyl- aminocarbonyl phenylmethyl 3-Methoxy methyl phenyl H H 2,6-dimethyl-4- H carbonyl- hydroxy phenylmethyl 1-Benzyloxy methyl phenyl H H 2,6-dimethyl-4- H carbonyl- hydroxy piperadin-4- ylmethyl Furan-2-yl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy Furan-3-yl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy Cyclohexyl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy Pyridin-4-yl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy Benzyl methyl 4-chloro Me H 2,6-dimethyl-4- H phenyl aminocarbonyl Benzyl methyl 3-fluoro H H 2,6-dimethyl-4- H phenyl aminocarbonyl Isopropyl H 3-cyano Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 2,5-difluoro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 4-methane Me H 2,6-dimethyl-4- H sulfonyl hydroxy phenyl Benzyl benzyl phenyl H H 2,6-dimethyl-4- H oxy aminocarbonyl methyl Isopropyl H Br Me H 2,6-dimethyl-4- H hydroxy Isopropyl H 4-dimethyl Me H 2,6-dimethyl-4- H amino hydroxy phenyl Isopropyl H 3-dimethyl Me H 2,6-dimethyl-4- H amino hydroxy carbonyl phenyl Isopropyl H 3-hydroxy Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 4-amino Me H 2,6-dimethyl-4- H carbonyl hydroxy phenyl Isopropyl H 3-chloro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 2,4-difluoro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 3-methane Me H 2,6-dimethyl-4- H sulfonyl hydroxy phenyl Isopropyl H 3-amino Me H 2,6-dimethyl-4- H carbonyl hydroxy phenyl Benzyl methyl 4-trifluoro Me H 2,6-dimethyl-4- H methyl aminocarbonyl phenyl 3,4-Dimethoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl aminocarbonyl Benzyl methyl 4-fluoro H H 2,6-dimethyl-4- H phenyl aminocarbonyl 4-Dimethylamino- methyl phenyl H Me 2,6-dimethyl-4- H phenylmethyl hydroxy 4-Methylamino- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 4-Methylcarbonyl methyl phenyl H H 2,6-dimethyl-4- H amino-phenyl hydroxy methyl 4-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 4-Hydroxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy Benzyl methyl 4-fluoro H H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl methyl 4-fluoro H H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl hydroxy phenyl H H 2,6-dimethyl-4- H methyl aminocarbonyl Isopropyl H phenyl H H 2,6-dimethyl, 4- H aminocarbonyl 3,4-Dichloro- H phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 4-Methylcarbonyl methyl phenyl H H 2,6-dimethyl-4- H oxy-phenyl hydroxy methyl 4-Methoxy methyl phenyl H H 2,6-dimethyl-4- H carbonyl- hydroxy phenylmethyl 3-Aminocarbonyl- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 3-Cyano-phenyl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy Pyridin-3-yl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy Pyridin-2-yl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy 1-(R)-Phenylethyl H phenyl H H 2,6-dimethyl-4- H aminocarbonyl 1-(R)-Phenylethyl H phenyl H H 2,6-dimethyl-4- H aminocarbonyl 2-Methoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 2,6-Dichloro- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 3-Phenoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy Naphthalen-1-yl- methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy Naphthalen-2-yl- methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy 3-Bromo-phenyl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy 3,4-Dimethoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 2,4-Dichloro- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy Benzyl isobutyl phenyl H H 2,6-dimethyl-4- H hydroxy Benzyl benzyl phenyl H H 2,6-dimethyl-4- H hydroxy Benzyl isopropyl phenyl H H 2,6-dimethyl-4- H hydroxy Benzyl H phenyl H H 2,6-dimethyl-4- H aminocarbonyl 3-Phenyl methyl phenyl H H 2,6-dimethyl-4- H prop-1-yl aminocarbonyl 2-Phenylethyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl 1-Phenylethyl methyl phenyl H H 2,6-dimethyl-4- H diastereomer A aminocarbonyl 1-Phenylethyl methyl phenyl H H 2,6-dimethyl-4- H diasteromer B aminocarbonyl Benzyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Isopropyl H 4-biphenyl Me H 2,6-dimethyl-4- H hydroxy Isopropyl H 3-fluoro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 2-fluoro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl hydroxy phenyl H H 2,6-dimethyl-4- H methyl hydroxy H hydroxy phenyl H H 2,6-dimethyl-4- H methyl hydroxy Isopropyl 3-(amino phenyl H H 2,6-dimethyl-4- H methyl) hydroxy phenyl methyl Isopropyl 3-amino phenyl H H 2,6-dimethyl-4- H carbonyl hydroxy phenyl methyl Isopropyl 3-cyano phenyl H H 2,6-dimethyl-4- H phenyl hydroxy methyl Isopropyl H 4-carboxy Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H pyridin-3-yl Me H 2,6-dimethyl-4- H hydroxy Isopropyl H 4-methoxy Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 3,5-difluoro Me H 2,6-dimethyl-4- H phenyl hydroxy Cyclohexyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Carboxymethyl H phenyl H H 2,6-dimethyl-4- H hydroxy Isopropyl H 3-hydroxy Me H 2,6-dimethyl-4- H methyl hydroxy phenyl Isopropyl H pyrimidin-5- Me H 2,6-dimethyl-4- H yl hydroxy Isopropyl H pyrimidin-5- Me H 4-hydroxy H yl Isopropyl H 3-carboxy Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 3-biphenyl Me H 2,6-dimethyl-4- H hydroxy Isopropyl H 2-methoxy Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl benzyl phenyl H H 3-aminocarbonyl H Isopropyl isopropyl phenyl H H 3-aminocarbonyl H Isopropyl benzyl phenyl H H 2,6-dimethyl-4- H oxy hydroxy methyl Isopropyl isobutyl phenyl H H 2,6-dimethyl-4-[2- H (2,6-dimethyl-4- hydroxyphenyl)-1- amino- ethylcarbonxyloxy] phenyl Isopropyl isobutyl phenyl H H 2,6-dimethyl-4- H hydroxy Isopropyl H 3,5-dichloro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 3-methoxy Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Isopropyl H 2-biphenyl Me H 2,6-dimethyl-4- H hydroxy Isopropyl H thiophen-3- Me H 2,6-dimethyl-4- H yl hydroxy Isopropyl H 4-chloro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 3-methyl Me H 2,6-dimethyl-4- H carbonyl hydroxy amino phenyl Isopropyl H 4-trifluoro Me H 2,6-dimethyl-4- H methyl hydroxy phenyl Isopropyl H naphthal Me H 2,6-dimethyl-4- H en-2-yl hydroxy Isopropyl H 2-trifluoro Me H 2,6-dimethyl-4- H methyl hydroxy phenyl Isopropyl H thiophen-3-yl Me H 4-hydroxy H Isopropyl H pyridin-3-yl Me H 4-hydroxy H Isopropyl H phenyl Me H 4-hydroxy H Isopropyl H 2-chloro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H naphthal Me H 2,6-dimethyl-4- H en-1-yl hydroxy Isopropyl benzyl phenyl H H 3-cyano H Isopropyl benzyl phenyl H H 4-hydroxy H Isopropyl benzyl phenyl H H 2,6-dimethyl-4- H hydroxy Isopropyl isopropyl phenyl H H 3-cyano H Isopropyl isopropyl phenyl H H 4-hydroxy H Isopropyl isopropyl phenyl H H 2,6-dimethyl-4- H hydroxy Isopropyl H 4-fluoro Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H 3,5-bis- Me H 2,6-dimethyl-4- H trifluoro hydroxy methyl phenyl Isopropyl H 2-methyl Me H 2,6-dimethyl-4- H phenyl hydroxy Isopropyl H phenyl Me H 2,6-dimethyl-4- H hydroxy 2-Dimethylamino- H phenyl H H 2,6-dimethyl-4- H 1-methyl-eth-1-yl hydroxy Methyl isobutyl phenyl H H 3-aminocarbonyl H Methyl isobutyl phenyl H H 3-cyano H Ethyl isopropyl phenyl H H 2,6-dimethyl-4- H hydroxy Methyl isopropyl phenyl H H 4-hydroxy H H 3-amino phenyl H H 2,6-dimethyl-4- H carbonyl hydroxy phenyl methyl H 3-cyano phenyl H H 2,6-dimethyl-4- H phenyl hydroxy methyl Methyl isobutyl phenyl H H 2,6-dimethyl-4- H hydroxy H benzyl phenyl H H 2,6-dimethyl-4- H oxy hydroxy methyl H isobutyl phenyl H H 2,6-dimethyl-4- H hydroxy H benzyl phenyl H H 2,6-dimethyl-4- H hydroxy Isopropyl H phenyl H H 2,6-dimethyl-4- H aminocarbonyl Methyl methyl phenyl H H 2,6-dimethyl-4- H morpholin-1- ylcarbonyl Methyl methyl phenyl H H 2,6-dimethyl-4- H ethylamino carbonyl Methyl methyl phenyl H H 2,6-dimethyl-4- H methylamino carbonyl H isopropyl phenyl H H 3-aminocarbonyl H H isopropyl phenyl H H 3-cyano H H isopropyl phenyl H H 2,6-dimethyl-4- H hydroxy H isopropyl phenyl H H 4-hydroxy H Methyl methyl phenyl H H 4-aminosulfonyl H Cyclohexyl H phenyl H H 2,6-dimethyl-4- H hydroxy Cyclohexyl H phenyl H H 2,6-dimethyl-4- H 4-hydroxy Cyclopropyl H phenyl H H 2,6-dimethyl-4- H methyl hydroxy Cyclopropyl H phenyl H H 4-hydroxy H methyl Isopropyl H phenyl H H 2,6-dimethyl-4- H hydroxy Isopropyl H phenyl H H 4-hydroxy H Methyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Ethyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Methyl H phenyl H H 4-hydroxy H Methyl H phenyl H H 2,6-dimethyl-4- H hydroxy Methyl methyl phenyl H H 4-aminocarbonyl H Methyl methyl benzyl H H 4-hydroxy H Methyl methyl benzyl H H 2,6-dimethyl-4- H hydroxy Methyl methyl phenyl H H 2,6-dimethyl-4- H hydroxy H methyl phenyl H H 2,6-dimethyl-4- H hydroxy Methyl methyl phenyl H H 4-hydroxy H H methyl phenyl H H 4-hydroxy H Ethyl methyl phenyl H H 4-hydroxy H Ethyl methyl phenyl H H 2,6-dimethyl-4- H hydroxy Benzyl methyl phenyl H H 2,6-dimethyl-4- H hydroxy Benzyl methyl phenyl H H 4-hydroxy H Isopropyl methyl phenyl H H 2,6-dimethyl-4- H hydroxy Isopropyl methyl phenyl H H 4-hydroxy H 2-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H phenyl aminocarbonyl methyl 3-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H phenyl aminocarbonyl methyl 2-Bromo-4,5- methyl phenyl H H 2,6-dimethyl-4- H dimethoxy- aminocarbonyl phenylmethyl 2-Carboxy-4,5- methyl phenyl H H 2,6-dimethyl-4- H dimethoxy- aminocarbonyl phenylmethyl 3-Carboxy-4- methyl phenyl H H H H methoxy-phenyl methyl 3-Carboxy-4- methyl phenyl H H 2,6-dimethyl H methoxy-phenyl methyl 3-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl H 4-methoxy- phenylmethyl 3,4-Dimethoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl imidazol-2-yl 3,4-Dimethoxy- methyl phenyl H H 2,6-dimethyl H phenylmethyl 3-Carboxy-4- methyl 4-chloro H H 2,6-dimethyl-4- H methoxy-phenyl aminocarbonyl methyl 3-Carboxy-4- methyl 4-chloro H H 2,6-dimethyl-4- H methoxy-phenyl aminocarbonyl methyl 3-Carboxy-4- methyl 4-chloro H H 2,6-dimethyl-4- H methoxy-phenyl aminocarbonyl methyl 4-Carboxy- methyl 4-chloro Me H 2,6-dimethyl-4- H phenylmethyl phenyl aminocarbonyl 3-Carboxy-4- methyl 4-chloro Cl H 2,6-dimethyl-4- H methoxy-phenyl phenyl aminocarbonyl methyl 3-(1H-tetrazol-5- methyl phenyl H H 2,6-dimethyl-4- H yl)-phenylmethyl aminocarbonyl 3-Carboxy-4- methyl phenyl H H 2,6-dimethyl-4- H trifluoromethoxy- aminocarbonyl phenylmethyl Bis-3,4- methyl phenyl H H 2,6-dimethyl-4- H trifluoromethoxy- aminocarbonyl phenylmethyl 3-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl aminocarbonyl Quinolin-4-yl methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy 4-Methoxy methyl phenyl H H 2,6-dimethyl-4- H naphthalen-1- hydroxy ylmethyl 4-Trifluoromethoxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 4-Trifluoromethyl- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 4-Isopropyloxy- methyl phenyl H H 2,6-dimethyl-4- H phenylmethyl hydroxy 3-Ethoxyphenyl- methyl phenyl H H 2,6-dimethyl-4- H methyl hydroxy 5-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl-4- H pyridin-2-yl aminocarbonyl methyl 5-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H pyridin-2- aminocarbonyl ylmethyl 6-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H pyridin-3- aminocarbonyl ylmethyl 6-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl-4- H pyridin-3- aminocarbonyl ylmethyl 5-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H furan-2-ylmethyl aminocarbonyl 5-Methoxy methyl phenyl H H 2,6-dimethyl-4- H carbonyl- aminocarbonyl furan-2-ylmethyl 3,4-Dimethoxy- hydroxy phenyl H H 2,6-dimethyl-4- H phenylmethyl methyl aminocarbonyl Benzyl hydroxy phenyl H H 2,6-dimethyl-4- H methyl aminocarbonyl 3-Carboxy-4- methyl phenyl H H 2,6-dimethyl-4- H methoxy-phenyl hydroxy methyl 3-Carboxy-4- methyl phenyl H H 4-hydroxy H methoxy-phenyl methyl 3-Carboxy-4- methyl phenyl H H 4-hydroxy H/Me methoxy-phenyl methyl 3-Carboxy-4- H phenyl H H 4-hydroxy H methoxy-phenyl methyl 3-Carboxy-4- H phenyl H H 4-hydroxy H/Me methoxy-phenyl methyl 3-Carboxy-4- H phenyl H H 2,6-dimethyl-4- H methoxy-phenyl hydroxy methyl 3-Methoxycarbonyl- methyl phenyl H H H H 4-methoxy- phenylmethyl 3-(1H-tetrazol-5- methyl phenyl H H 4-aminocarbonyl H yl)-phenylmethyl 3-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl-4- H 4-methoxy- hydroxy phenylmethyl 3-Methoxycarbonyl methyl phenyl H H 4-aminocarbonyl H 3-Carboxy methyl phenyl H H 4-aminocarbonyl H 3-Methoxycarbonyl H phenyl H H 2,6-dimethyl-4- H aminocarbonyl 3-Carboxy H phenyl H H 2,6-dimethyl-4- H aminocarbonyl 3-Carboxy-4- methyl phenyl H H 4-benzyloxy- H/Me methoxy- phenylmethyl 3-Carboxy-4- methyl phenyl H H 4-aminocarbonyl H methoxy- phenylmethyl 3-Carboxy- methyl 4-chloro Me H 4-aminocarbonyl H phenyl 3-Methoxycarbonyl- methyl phenyl H H 4-hydroxy H 4-methoxy- phenylmethyl 5-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl-4- H furan-2-ylmethyl hydroxy 5-Carboxy-furan- methyl phenyl H H 2,6-dimethyl-4- H 2-ylmethyl hydroxy 3-Carboxy-4- methyl 3-bromo H H 2,6-dimethyl-4- H methoxy- phenyl aminocarbonyl phenylmethyl 3-Carboxy-4- methyl 4-iodo H H 2,6-dimethyl-4- H methoxy- aminocarbonyl phenylmethyl 3-Carboxy-4- methyl 2-bromo H H 2,6-dimethyl-4- H methoxy- phenyl aminocarbonyl phenylmethyl 3-Carboxy-4- methyl 4-bromo H H 2,6-dimethyl-4- H methoxy- aminocarbonyl phenylmethyl 3-Carboxy-4- methyl phenyl H H 2,6-dimethyl H methoxy- phenylmethyl 3-Carboxy-4- methyl 4-chloro methyl H 4-hydroxy H methoxy- phenylmethyl 3-Aminocarbonyl- methyl phenyl H H 2,6-dimethyl-4- H 4-methoxy aminocarbonyl phenylmethyl 3-(Morpholin-4- methyl phenyl H H 2,6-dimethyl-4- H ylcarbonyl)-4- aminocarbonyl methoxy phenylmethyl -3-Aminocarbonyl- methyl phenyl H H 4-hydroxy H 4-methoxy- phenylmethyl 3-(Morpholin-4- methyl phenyl H H 4-hydroxy H ylcarbonyl)-4- methoxy- phenylmethyl 3-(2-Hydroxy methyl phenyl H H 2,6-dimethyl-4- H eth-1-yl- aminocarbonyl aminocarbonyl)- 4-methoxy phenylmethyl 3-(Cyclopropyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl)- aminocarbonyl 4-methoxy- phenylmethyl 3-(Phenylamino methyl phenyl H H 2,6-dimethyl-4- H carbonyl)-4- aminocarbonyl methoxy- phenylmethyl 5-Methoxycarbonyl- methyl phenyl H H 4-aminocarbonyl H furan-2-ylmethyl 5-Carboxy-furan- methyl phenyl H H 4-aminocarbonyl H 2-ylmethyl 3-(Phenylamino methyl phenyl H H 2,6-dimethyl-4- H carbonyl)-4- hydroxy methoxy- phenylmethyl 3-(3-carboxyphenyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl)- hydroxy 4-methoxy- phenylmethyl 3-(1H-Tetrazol-5- methyl phenyl H H 2,6-dimethyl-4- H yl)-4-methoxy- hydroxy phenylmethyl 3-(4-Carboxyphenyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl)- hydroxy 4-methoxy- phenylmethyl 3-(2-t-Butyl- methyl phenyl H H 2,6-dimethyl-4- H tetrazol-5-yl)-4- aminocarbonyl methoxy- phenylmethyl 3-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl-4- Methoxy- 4-methoxy- aminocarbonyl carbonyl phenylmethyl 2-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl-4- H pyridin-4-yl aminocarbonyl methyl 4-Methoxycarbonyl methyl phenyl H H 2,6-dimethyl-4- H pyridin-2-yl aminocarbonyl methyl 6-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl-4- H pyridin-2- aminocarbonyl ylmethyl 3-Methoxycarbonyl- methyl phenyl H H 2,6-dimethyl-4- Methoxy- 4-methoxy- aminocarbonyl carbonyl phenylmethyl 2-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H pyridin-4- aminocarbonyl ylmethyl and 6-Carboxy- methyl phenyl H H 2,6-dimethyl-4- H. pyridin-2- aminocarbonyl ylmethyl 37. A compound of Formula (Ic) Formula (Ic) wherein L is O and R1, R2, R3-1, R3-2, R5, Ra, Rb, and R41 are dependcently selected from the group consisting of: R1 R2 R3-1 R3-2 R5 R41 Ra/Rb 3,4-Dimethoxy- benzyloxy phenyl H H 2,6-dimethyl-4- H phenylmethyl methyl hydroxy Isopropyl hydroxy phenyl H H 2,6-dimethyl-4- H methyl hydroxy Isopropyl methyl 4- 2,6-dimethyl-4- H fluorophenyl hydroxy 2-Phenylethyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Benzyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Cyclohexyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Methyl methyl phenyl H H 2,6-dimethyl-4- H aminocarbonyl Methyl methyl phenyl H H 2,6-dimethyl-4- H (morpholin-4- carbonyl) Methyl methyl phenyl H H 2,6-dimethyl-4- H ethylamino carbonyl Methyl methyl phenyl H H 2,6-dimethyl-4- H methylamino carbonyl Methyl methyl phenyl H H 4-aminocarbonyl H Methyl methyl phenyl H H 2,6-dimethyl-4- H hydroxy H methyl phenyl H H 2,6-dimethyl-4- H hydroxy Methyl methyl phenyl H H 4-hydroxy H H methyl phenyl H H 4-hydroxy H Ethyl methyl phenyl H H 4-hydroxy H Ethyl methyl phenyl H H 2,6-dimethyl-4- H hydroxy Benzyl methyl phenyl H H 2,6-dimethyl-4- H hydroxy Benzyl methyl phenyl H H 4-hydroxy H Isopropyl methyl phenyl H H 4-hydroxy H Isopropyl methyl phenyl H H 2,6-dimethyl-4- H hydroxy 3-Carboxy- methyl 4- Me H 2,6-dimethyl-4- H phenyl chlorophenyl aminocarbonyl methyl 3-Carboxy- methyl 4- Me H 4-aminocarbonyl H phenyl chlorophenyl 3-Carboxy-4- methyl 4- Me H 2,6-dimethyl-4- H methoxy- chlorophenyl aminocarbonyl phenylmethyl 3- methyl phenyl H H 2,6-dimethyl-4- H Methoxycarbon- aminocarbonyl yl-4-methoxy- phenylmethyl 3- methyl phenyl H H 4-aminocarbonyl H Methoxycarbon- yl-4-methoxy- phenylmethyl 3-Carboxy-4- methyl phenyl H H 2,6-dimethyl-4- H methoxy- aminocarbonyl phenylmethyl 3-Carboxy-4- methyl phenyl H H 4-aminocarbonyl H methoxy- phenylmethyl 3-Carboxy-4- methyl 4- Me H 4-hydroxy H methoxy- chlorophenyl phenylmethyl 6-Methoxy- methyl phenyl H H 2,6-dimethyl-4- H carbonyl- aminocarbonyl pyridin-2-yl methyl and 3-Carboxy-4- methyl 4- H H 4-aminocarbonyl H. methoxy- chlorophenyl phenylmethyl 38. A compound of Formula (Id) Formula (Id) wherein L is O and R1, R2, R3-1, R3-2, R5, Ra, Rb, and R41 are dependently selected from the group consisting of: R1 R2 R3-1 R3-2 R5 R41 Ra/Rb 3-Carboxy-4- methyl phenyl H H 4-amino- H. methoxyphenyl carbonyl methyl 39. A compound of Formula (Ie) Formula (Ie) wherein L is O and R1, R2, R3-1, R3-2, R5, Ra, Rb, and R41 are dependently selected from the group consisting of: R1 R2 R3-1 R3-2 R5 R41 Ra/Rb 3- methyl phenyl H H 4-amino- H Methoxycarbon- carbonyl yl-4-methoxy- phenylmethyl and 3-Carboxy-4- methyl phenyl H H 4-amino- H. methoxy- carbonyl phenylmethyl 40. A compound selected from the group consisting of and 41. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. 42. The compound of claim 1 that is the hydrochloride salt of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid dihydrochloride. 43. The composition of claim 41 wherein the compound is the hydrochloride salt of 5-({[2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid.