HIV protease inhibiting compounds
| Title: | HIV protease inhibiting compounds |
|---|---|
| Patent Number: | 8,653,141 |
| Publication Date: | February 18, 2014 |
| Appl. No: | 13/451370 |
| Application Filed: | April 19, 2012 |
| Abstract: | A compound of the formula [chemical expression included] is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed. |
| Inventors: | Flentge, Charles A. (Salem, WI, US); Chen, Hui-Ju (Grayslake, IL, US); DeGoey, David A. (Salem, WI, US); Flosi, William J. (Evanston, IL, US); Grampovnik, David J. (Waukegan, IL, US); Huang, Peggy P. (Lake Bluff, IL, US); Kempf, Dale J. (Libertyville, IL, US); Klein, Larry L. (Lake Forest, IL, US); Krueger, Allan C. (Gurnee, IL, US); Madigan, Darold L. (Elk Grove Village, IL, US); Randolph, John T. (Libertyville, IL, US); Sun, Minghua (Libertyville, IL, US); Yeung, Ming C. (Grayslake, IL, US); Zhao, Chen (Libertyville, IL, US) |
| Assignees: | AbbVie Inc. (North Chicago, IL, US) |
| Claim: | 1. A compound of formula (I), [chemical expression included] or a pharmaceutically acceptable salt form, stereoisomer, ester, salt of an ester, or combination thereof, wherein: A is R 5 C(O)—, R 6 SO 2 —, [chemical expression included] X is O, S or NH; R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R is substituted with 0, 1, or 2 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro, hydroxy, alkoxy, —NH 2 , —N(H)alkyl, —N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R 1 is OR a , —OSO 2 R a , —OSO 3 R a , —OPO 3 R a , —OC(═O)C(H)(R 1a)NR a R b or —OC(═O)C(H)(R 1a)N(H)C(O)OR a ; R 1a is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R 1a is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, —OR a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —C(═O)R a , —NR a R b , —N(R b)C(═O)R a , —N(R b)C(═O)OR a , —N(R b)SO 2 R a , —N(R a)SO 2 NR a R b , —N(R b)C(═NH)NR a R b , —N(R b)C(═O)NR a R b , —C(═O)NR a R b and —C(═O)OR a ; R 2 is H; R 3 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl, heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylNR a R b , -alkylN(R b)C(═O)OR a , -alkylN(R b)C(═O)R a , -alkylN(R b)SO 2 R a or -alkylN(R b)SO 2 NR a R b ; wherein each of the cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkyl moiety of the cycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroaryl moiety of the heteroarylalkyl, aryl moiety of the arylalkyl is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO 2 (alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , —C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO 2 (alkyl), -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl) 2 , -alkylC(═O)alkyl and R 3a ; R 3a is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, wherein each R 3a is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO 2 (alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(O)N(alkyl) 2 , —C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO 2 (alkyl), -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl) 2 and -alkylC(═O)alkyl; R 4 is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl wherein each R 4 is substituted with —C(R 4b)═NOR 4a and 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of halo, alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR 4a , —SR 4a , —SOR 4a , —SO 2 R 4a , —NR 4a R 4b , —OC(═O)R 4a , —C(═O)R 4a , —C(═O)OR 4a , —C(═O)NR 4a R 4b , —N(R 4b)C(═O)R 4a , N(R 4b)C(═O)OR 4a , —N(R 4b)SO 2 R 4a , —N(R 4b)C(═O)NR 4a R 4b , —N(R 4b)SO 2 NR 4a R 4b , -alkylSR 4a , -alkylSOR 4a , -alkylSO 2 R 4a , -alkylNR 4a R 4b , -alkylOC(═O)R 4a , -alkylC(═O)R 4a , -alkylC(═O)OR 4a , -alkylC(═O)NR 4a R 4b , -alkylN(R 4b)C(═O)R 4a , -alkylN(R 4b)C(═O)OR 4a , -alkylN(R 4b)SO 2 R 4a , -alkylN(R 4b)C(═O)NR 4a R 4b , -alkylN(R 4b)SO 2 NR 4a R 4b , —N(H)C(═O)alkylN(H)C(═O)OR 4a , —N(H)C(═O)alkylNR 4a R 4b , —C(NR 4a R 4b)═NOR 4a and —C(R 4b)═NOC(═O)alkylNR 4a R 4b ; R 4a and R 4b , at each occurrence, are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl, heteroaryl and heteroalkyl; wherein each R 4a and R 4b , at each occurrence, is independently substituted with 0, 1 or 2 substituents independently selected from the group consisting of alkyl, alkenyl, hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH 2 , —N(H)alkyl, —N(alkyl) 2 , —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)alkyl, —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, cyanoalkyl, nitroalkyl, formylalkyl and alkoxyalkyl; R 5 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -OalkylSO 2 alkyl, —O-heterocycle, -alkyl-O-aryl or —O-alkyl-heteroaryl; wherein the heterocycle, aryl or heteroaryl moiety of —O-heterocycle, -alkyl-O-aryl and —O-alkyl-heteroaryl is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl) 2 ; R 6 is aryl or heteroaryl; wherein each R 6 is substituted with 0 or 1 substituent selected from the group consisting of —C(H)═NOH, —C(alkyl)═NOH, —C(H)═NO(alkyl), —C(alkyl)═NO(alkyl), —C(H)═NO(arylalkyl) and —C(alkyl)═NO(arylalkyl); R 7 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R 7 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, —OR a , -OalkylC(═O)NR a R b , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —C(═O)R a , —NR a R b , —N(R b)C(═O)R a , —N(R b)C(═O)OR a , —N(R b)SO 2 R a , —N(R b)SO 2 NR a R b , —N(R b)C(═NH)NR a R b , —N(R b)C(═O)NR a R b , —C(═O)NR a R b , —C(═O)OR a and R 7a ; R 7a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 7a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl) 2 ; R 8 is —C(═O)OR 8a or —C(═O)alkylNR 8a R 8b , R 8a and R 8b are, at each occurrence, independently selected from the group consisting of alkyl, arylalkyl and heteroarylalkyl; wherein each R 8a and R 8b is independently substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of alkyl, nitro, hydroxy, alkoxy, amino, formyl, halo, haloalkyl, hydroxyalkyl, alkoxyalky aminoalkyl and formylalkyl; R 9 is alkyl, alkenyl, alkynyl, —C(═O)NR a R b , —C(═O)OR a , cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein each R 9 is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR a , —OC(═O)R a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a , —SO 2 OR a , —NR a R b , —N(R b)NR a R b , —N(R b)C(═O)R a , —N(R b)SO 2 R a , —N(R b)C(═O)OR a , —N(R b)C(═O)NR a R b , —N(R b)SO 2 NR a R b , —C(═O)R a , —C(═O)NR a R b , —C(═O)OR a , azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR a , -alkylOC(═O)R a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylSO 2 NR a , -alkylSO 2 OR a , -alkylNR a R b , —C(H)═N(OR a), —C(alkyl)═N(OR a), —C(H)═NNR a R b , —C(alkyl)═NNR a R b , —C(H)(═NOR a)NR a R b , —C(alkyl)(═NOR a)NR a R b , -alkylN(R b)NR a R b , -alkylN(R b)C(═O)R a , -alkylN(R b)C(═O)OR a , -alkylN(R b)C(═O)NR a R b , -alkylN(R b)SO 2 NR a R b , -alkylN(R b)SO 2 R a , -alkylC(═O)R a , -alkylC(═O)OR a , -alkylC(═O)NR a R b and R 9a ; R 9a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 9a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl) 2 ; R 10 is alkyl, alkenyl, alkynyl, —C(═O)NR a R b , —C(═O)OR a , cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein each R 10 is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR a , —OC(═O)R a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a , —SO 2 OR a , —NR a R b , —N(R b)NR a R b , —N(R b)C(═O)R a , —N(R b)SO 2 R a , —N(R b)C(═O)OR a , —N(R b)C(═O)NR a R b , —N(R b)SO 2 NR a R b , —C(═O)R a , —C(═O)NR a R b , —C(═O)OR a , azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR a , -alkylOC(═O)R a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylSO 2 NR a , -alkylSO 2 OR a , -alkylNR a R b , —C(H)═N(OR a), —C(alkyl)═N(OR a), —C(H)═NNR a R b , —C(alkyl)═NNR a R b , —C(H)(═NOR a)NR a R b , —C(alkyl)(═NOR a)NR a R b , -alkylN(R b)NR a R b , -alkylN(R b)C(═O)R a , -alkylN(R b)C(═O)OR a , -alkylN(R b)C(═O)NR a R b , -alkylN(R b)SO 2 NR a R b , -alkylN(R b)SO 2 R a , -alkylC(═O)R a , -alkylC(═O)OR a , -alkylC(═O)NR a R b and R 10a ; R 10a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 10a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl) 2 ; R 11 is alkyl, alkenyl, alkynyl, —C(═O)NR a R b , —C(═O)OR a , cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein each R 11 is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR a , —OC(═O)R a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a , —SO 2 OR a , —NR a R b , —N(R b)NR a R b , —N(R b)C(═O)R a , —N(R b)SO 2 R a , —N(R b)C(═O)OR a , —N(R b)C(═O)NR a R b , —N(R b)SO 2 NR a R b , —C(═O)R a , —C(═O)NR a R b , —C(═O)OR a , azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR a , -alkylOC(═O)R a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylSO 2 NR a , -alkylSO 2 OR a , -alkylNR a R b , —C(H)═N(OR a), —C(alkyl)═N(OR a), —C(H)═NNR a R b , —C(alkyl)═NNR a R b , —C(H)(═NOR a)NR a R b , —C(alkyl)(═NOR a)NR a R b , -alkylN(R b)NR a R b , -alkylN(R b)C(═O)R a , -alkylN(R b)C(═O)OR a , -alkylN(R b)C(═O)NR a R b , -alkylN(R b)SO 2 NR a R b , -alkylN(R b)SO 2 R a , -alkylC(═O)R a , -alkylC(═O)OR a , -alkylC(═O)NR a R b and R 11a ; R 11a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 11a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl) 2 ; R 12 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl or cycloalkenylalkyl; wherein each R 12 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, alkoxy cyano, nitro and halo; R 13 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein each R 13 is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR a , —OC(═O)R a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a , —SO 2 OR a , —NR a R b , —N(R b)NR a R b , —N(R b)C(═O)R a , —N(R b)SO 2 R a , —N(R b)C(═O)OR a , —N(R b)C(═O)NR a R b , —N(R b)SO 2 NR a R b , —C(═O)R a , —C(═O)NR a R b , —C(═O)OR a , azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR a , -alkylOC(═O)R a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylSO 2 NR a , -alkylSO 2 OR a , -alkylNR a R b , —C(H)═N(OR a), —C(alkyl)═N(OR a), —C(H)═NNR a R b , —C(alkyl)═NNR a R b , —C(H)(═NOR a)NR a R b , —C(alkyl)(═NOR a)NR a R b , -alkylN(R b)NR a R b , -alkylN(R b)C(═O)R a , -alkylN(R b)C(═O)OR a , -alkylN(R b)C(═O)NR a R b , -alkylN(R b)SO 2 NR a R b , -alkylN(R b)SO 2 R a , -alkylC(═O)R a , -alkylC(═O)OR a , -alkylC(═O)NR a R b and R 13a ; R 13a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 13a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl) 2 ; R a and R b at each occurrence are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocycle; wherein each R a and R b , at each occurrence, is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl) 2 and R c ; alternatively, R a and R b , together with the nitrogen atom they are attached, form a heterocycle ring substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl) 2 and R c ; R c is aryl, heteroaryl or heterocycle; wherein each R c is independently substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkyl-N(H)(alkyl), -alkyl-N(alkyl) 2 , -alkyl-N(H)C(═O)NH 2 , -alkyl-N(H)C(═O)N(H)(alkyl), -alkyl-N(H)C(═O)N(alkyl) 2 , -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl, -alkyl-C(═O)NH 2 , -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl) 2 ; and n is 1 or 2. |
| Claim: | 2. The compound of claim 1 wherein R 1 is OH and R 2 is H. |
| Claim: | 3. The compound of claim 1 wherein R 1 is OH, R 2 is H, X is O, and R 3 is alkyl, cycloalkenylalkyl, cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSR a , -alkylSOR a , -alkylSO 2 R a or -alkylNR a R b . |
| Claim: | 4. The compound of claim 1 wherein R 1 is OH, R 2 is H, X is O, R 3 is alkyl or cycloalkylalkyl, R 4 is aryl or heteroaryl, and R 4a and R 4b are each hydrogen. |
| Claim: | 5. The compound of claim 1 wherein R 1 is OH, R 2 is H, R 3 is alkyl or cycloalkylalkyl, X is O, and R 4 is phenyl substituted with 0, 1, 2, 3 or 4 substituents selected from the group consisting of halo, —OR 4a and —NR 4a R 4b ; wherein R 4a and R 4b are independently selected from the group consisting of hydrogen and alkyl. |
| Claim: | 6. The compound of claim 1 or a pharmaceutically acceptable salt form, stereoisomer, ester, salt of an ester, or combination thereof, selected from the group consisting of hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; tetrahydro-3-furanyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}acetamide; N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(2,6-dimethylphenoxy)acetamide; (3aS,7aR)-hexahydro-4H-furo[2,3-b]pyran-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate and (3aR,7aS)-hexahydro-4H-furo[2,3-b]pyran-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; 3-furylmethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; 2-pyridinylmethyl 2-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-2-oxoethylcarbamate; 2-(methylsulfonyl)ethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; (3aS,7aR)-hexahydro-4H-furo[2,3-b]pyran-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; (3aR,7aS)-hexahydro-4H-furo[2,3-b]pyran-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; 3-pyridinylmethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; 4-pyridinylmethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; 1,3-thiazol-5-ylmethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate; and N-{(2R,3S)-2-hydroxy-3-[({4-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-4-phenylbutyl}-4-[(E)-(hydroxyimino)methyl]-N-isobutylbenzenesulfonamide. |
| Claim: | 7. The compound of claim 1 having formula (II) [chemical expression included] or a pharmaceutically acceptable salt form, stereoisomer, ester, salt of an ester, or combination thereof, wherein R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R is substituted with 0, 1, or 2 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro, hydroxy, alkoxy, —NH 2 , —N(H)alkyl, —N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R 1 is OR a , —OSO 2 R a , —OSO 3 R a , —OPO 3 R a , —OC(═O)C(H)(R 1a)NR a R b or —OC(═O)C(H)(R 1a)N(H)C(O)OR a ; R 1a is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R 1a is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, —OR a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —C(═O)R a , —NR a R b , —N(R b)C(═O)R a , —N(R b)C(═O)OR a , —N(R b)SO 2 R a , —N(R a)SO 2 NR a R b , —N(R b)C(═NH)NR a R b , —N(R b)C(═O)NR a R b , —C(═O)NR a R b and —C(═O)OR a ; R 2 is H; R 3 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl, heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylNR a R b , -alkylN(R b)C(═O)OR a , -alkylN(R b)C(═O)R a , -alkylN(R b)SO 2 R a or -alkylN(R b)SO 2 NR a R b ; wherein each of the cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkyl moiety of the cycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroaryl moiety of the heteroarylalkyl, aryl moiety of the arylalkyl is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO 2 (alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , —C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO 2 (alkyl), -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl) 2 , -alkylC(═O)alkyl and R 3a ; R 3a is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, wherein each R 3a is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO 2 (alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(O)N(alkyl) 2 , —C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO 2 (alkyl), -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl) 2 and -alkylC(═O)alkyl; R 4 is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl wherein each R 4 is substituted with —C(R 4b)═NOR 4a and 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of halo, alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR 4a , —SR 4a , —SOR 4a , —SO 2 R 4a , —NR 4a R 4b , —OC(═O)R 4a , —C(═O)R 4a , —C(═O)OR 4a , —C(═O)NR 4a R 4b , —N(R 4b)C(═O)R 4a , —N(R 4b)C(═O)OR 4a , —N(R 4b)SO 2 R 4a , —N(R 4b)C(═O)NR 4a R 4b , —N(R 4b)SO 2 NR 4a R 4b , -alkylSR 4a , -alkylSOR 4a , -alkylSO 2 R 4a , -alkylNR 4a R 4b , -alkylOC(═O)R 4a , -alkylC(═O)R 4a , -alkylC(═O)OR 4a , -alkylC(═O)NR 4a R 4b , -alkylN(R 4b)C(═O)R 4a , -alkylN(R 4b)C(═O)OR 4a , -alkylN(R 4b)SO 2 R 4a , -alkylN(R 4b)C(═O)NR 4a R 4b , -alkylN(R 4b)SO 2 NR 4a R 4b , —N(H)C(═O)alkylN(H)C(═O)OR 4a , —N(H)C(═O)alkylNR 4a R 4b , —C(NR 4a R 4b)═NOR 4a and —C(R 4b)═NOC(═O)alkylNR 4a R 4b ; R 4a and R 4b , at each occurrence, are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl, heteroaryl and heteroalkyl; wherein each R 4a and R 4b , at each occurrence, is independently substituted with 0, 1 or 2 substituents independently selected from the group consisting of alkyl, alkenyl, hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH 2 , —N(H)alkyl, —N(alkyl) 2 , —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)alkyl, —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, cyanoalkyl, nitroalkyl, formylalkyl and alkoxyalkyl; R 7 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R 7 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, —OR a , -OalkylC(═O)NR a R b , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —C(═O)R a , —NR a R b , —N(R b)C(═O)R a , —N(R b)C(═O)OR a , —N(R b)SO 2 R a , —N(R b)SO 2 NR a R b , —N(R b)C(═NH)NR a R b , —N(R b)C(═O)NR a R b , —C(═O)NR a R b , —C(═O)OR a and R 7a ; R 7a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 7a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl) 2 ; R 8 is —C(═O)OR 8a or —C(═O)alkylNR 8a R 8b , R 8a and R 8b are, at each occurrence, independently selected from the group consisting of alkyl, arylalkyl and heteroarylalkyl; wherein each R 8a and R 8b is independently substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of alkyl, nitro, hydroxy, alkoxy, amino, formyl, halo, haloalkyl, hydroxyalkyl, alkoxyalky aminoalkyl and formylalkyl; R a and R b at each occurrence are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocycle; wherein each R a and R b , at each occurrence, is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl) 2 and R c ; alternatively, R a and R b , together with the nitrogen atom they are attached, form a heterocycle ring substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl) 2 and R c ; and R c is aryl, heteroaryl or heterocycle; wherein each R c is independently substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkyl-N(H)(alkyl), -alkyl-N(alkyl) 2 , -alkyl-N(H)C(═O)NH 2 , -alkyl-N(H)C(═O)N(H)(alkyl), -alkyl-N(H)C(═O)N(alkyl) 2 , -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl, -alkyl-C(═O)NH 2 , -alkyl —C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl) 2 . |
| Claim: | 8. The compound of claim 7 wherein R 1 is OH and R 2 is H. |
| Claim: | 9. The compound of claim 7 wherein R 1 is OH, R 2 is H and R 3 is alkyl, cycloalkenylalkyl, cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSR a , -alkylSOR a , -alkylSO 2 R a or -alkylNR a R b . |
| Claim: | 10. The compound of claim 7 wherein R 1 is OH, R 2 is H, R 3 is alkyl or cycloalkyl and R 4 is aryl or heteroaryl and R 4a and R 4b are each hydrogen. |
| Claim: | 11. The compound of claim 7 wherein R 1 is OH, R 2 is H, R 3 is alkyl or cycloalkylalkyl and R 4 is phenyl substituted with 0, 1, 2, 3 or 4 substituents selected from the group consisting of halo, —OR 4a and —NR 4a R 4b ; wherein R 4a and R 4b are independently selected from the group consisting of hydrogen and alkyl. |
| Claim: | 12. The compound of claim 7 wherein R 1 is OH, R 2 is H, R 3 is alkyl or cycloalkylalkyl, R 4 is phenyl substituted with 0, 1, 2, 3 or 4 substituents selected from the group consisting of halo, —OR 4a and —NR 4a R 4b , and R 7 is alkyl; wherein R 4a and R 4b are independently selected from the group consisting of hydrogen and alkyl. |
| Claim: | 13. The compound of claim 7 or a pharmaceutically acceptable salt form, stereoisomer, ester, salt of an ester, or combination thereof, selected from the group consisting of tert-butyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropylcarbamate; benzyl(1S)-3-amino-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-3-oxopropylcarbamate; methyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropylcarbamate; 2-pyridinylmethyl(1R)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylpropylcarbamate; 2-pyridinylmethyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylpropylcarbamate; benzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylpropylcarbamate; benzyl(1S,2R)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-hydroxypropylcarbamate; tert-butyl(1S,2S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylbutylcarbamate; benzyl(1S,2S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylbutylcarbamate; tert-butyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-3-(methylsulfonyl)propylcarbamate; benzyl(1R)-1-[(aminosulfonyl)methyl]-2-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-2-oxoethylcarbamate; benzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-3-(methylsulfanyl)propylcarbamate; benzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-3-methylbutylcarbamate; benzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropylcarbamate; benzyl(1S)-4-amino-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]butylcarbamate; benzyl(1S)-2-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-1-(1H-imidazol-4-ylmethyl)-2-oxoethylcarbamate; benzyl(1S)-2-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamate; benzyl(1S,2R)-2-(2-amino-2-oxoethoxy)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]propylcarbamate; methyl(3S)-4-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-3-{[(benzyloxy)carbonyl]amino}-4-oxobutanoate; 2-pyridinylmethyl(1S,2S)-1-[({(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2-methylbutylcarbamate; [6-(methoxymethyl)-2-pyridinyl]methyl(1S,2S)-1-[({(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2-methylbutylcarbamate; [6-(methoxymethyl)-2-pyridinyl]methyl(1S)-1-[({(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2,2-dimethylpropylcarbamate; (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanamide; (2R)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3-methylpentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[({[(5-nitro-3-thienyl)methyl]amino}acetyl)amino]pentanamide; and benzyl (1S)-4-{[amino(imino)methyl]amino}-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]butylcarbamate. |
| Claim: | 14. The compound of claim 1 having formula (VI) [chemical expression included] or a pharmaceutically acceptable salt form, stereoisomer, ester, salt of an ester, or combination thereof, wherein X is O, S or NH; R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R is substituted with 0, 1, or 2 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro, hydroxy, alkoxy, —NH 2 , —N(H)alkyl, —N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R 1 is H and R 2 is OR a , —OSO 2 R a , —OSO 3 R a , —OPO 3 R a , —OC(═O)C(H)(R 1a)NR a R b or —OC(═O)C(H)(R 1a)N(H)C(O)OR a ; or R 1 is OR a , —OSO 2 R a , —OSO 3 R a , —OPO 3 R a , —OC(═O)C(H)(R 1a)NR a R b or —OC(═O)C(H)(R 1a)N(H)C(O)OR a ; R 1a is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R 1a is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, —OR a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —C(═O)R a , —NR a R b , —N(R b)C(═O)R a , —N(R b)C(═O)OR a , —N(R b)SO 2 R a , —N(R a)SO 2 NR a R b , —N(R b)C(═NH)NR a R b , —N(R b)C(═O)NR a R b , —C(═O)NR a R b and —C(═O)OR a ; R 2 is H; R 3 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl, heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylNR a R b , -alkylN(R b)C(═O)OR a , -alkylN(R b)C(═O)R a , -alkylN(R b)SO 2 R a or -alkylN(R b)SO 2 NR a R b ; wherein each of the cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkyl moiety of the cycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroaryl moiety of the heteroarylalkyl, aryl moiety of the arylalkyl is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO 2 (alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , —C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO 2 (alkyl), -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl) 2 , -alkylC(═O)alkyl and R 3a ; R 3a is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, wherein each R 3a is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO 2 (alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(O)N(alkyl) 2 , —C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO 2 (alkyl), -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl) 2 and -alkylC(═O)alkyl; R 4 is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl wherein each R 4 is substituted with —C(R 4b)═NOR 4a and 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of halo, alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR 4a , —SR 4a , —SOR 4a , —SO 2 R 4a , —NR 4a R 4b , —OC(═O)R 4a , —C(═O)R 4a , —C(═O)OR 4a , —C(═O)NR 4a R 4b , —N(R 4b)C(═O)R 4a , —N(R 4b)C(═O)OR 4a , —N(R 4b)SO 2 R 4a , —N(R 4b)C(═O)NR 4a R 4b , —N(R 4b)SO 2 NR 4a R 4b , -alkylSR 4a , -alkylSOR 4a , -alkylSO 2 R 4a , -alkylNR 4a R 4b , -alkylOC(═O)R 4a , -alkylC(═O)R 4a , -alkylC(═O)OR 4a , -alkylC(═O)NR 4a R 4b , -alkylN(R 4b)C(═O)R 4a , -alkylN(R 4b)C(═O)OR 4a , -alkylN(R 4b)SO 2 R 4a , -alkylN(R 4b)C(═O)NR 4a R 4b , -alkylN(R 4b)SO 2 NR 4a R 4b , —N(H)C(═O)alkylN(H)C(═O)OR 4a , —N(H)C(═O)alkylNR 4a R 4b , —C(NR 4a R 4b)═NOR 4a and —C(R 4b)═NOC(═O)alkylNR 4a R 4b ; R 4a and R 4b , at each occurrence, are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl, heteroaryl and heteroalkyl; wherein each R 4a and R 4b , at each occurrence, is independently substituted with 0, 1 or 2 substituents independently selected from the group consisting of alkyl, alkenyl, hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH 2 , —N(H)alkyl, —N(alkyl) 2 , —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)alkyl, —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, cyanoalkyl, nitroalkyl, formylalkyl and alkoxyalkyl; R 7 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R 7 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, —OR a , -OalkylC(═O)NR a R b , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —C(═O)R a , —NR a R b , —N(R b)C(═O)R a , —N(R b)C(═O)OR a , —N(R b)SO 2 R a , —N(R b)SO 2 NR a R b , —N(R b)C(═NH)NR a R b , —N(R b)C(═O)NR a R b , —C(═O)NR a R b , —C(═O)OR a and R 7a ; R 7a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 7a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl) 2 ; R 12 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl or cycloalkenylalkyl; wherein each R 12 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, alkoxy cyano, nitro and halo; R 13 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein each R 13 is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR a , —OC(═O)R a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a , —SO 2 OR a , —NR a R b , —N(R b)NR a R b , —N(R b)C(═O)R a , —N(R b)SO 2 R a , —N(R b)C(═O)OR a , —N(R b)C(═O)NR a R b , —N(R b)SO 2 NR a R b , —C(═O)R a , —C(═O)NR a R b , —C(═O)OR a , azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR a , -alkylOC(═O)R a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylSO 2 NR a , -alkylSO 2 OR a , -alkylNR a R b , —C(H)═N(OR a), —C(alkyl)═N(OR a), —C(H)═NNR a R b , —C(alkyl)═NNR a R b , —C(H)(═NOR a)NR a R b , —C(alkyl)(═NOR a)NR a R b , -alkylN(R b)NR a R b , -alkylN(R b)C(═O)R a , -alkylN(R b)C(═O)OR a , -alkylN(R b)C(═O)NR a R b , -alkylN(R b)SO 2 NR a R b , -alkylN(R b)SO 2 R a , -alkylC(═O)R a , -alkylC(═O)OR a , -alkylC(═O)NR a R b and R 13a ; R 13a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 13a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl) 2 ; R a and R b at each occurrence are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocycle; wherein each R a and R b , at each occurrence, is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl) 2 and R c ; alternatively, R a and R b , together with the nitrogen atom they are attached, form a heterocycle ring substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkylN(H)(alkyl), -alkylN(alkyl) 2 , -alkylN(H)C(═O)NH 2 , -alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl) 2 , -alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH 2 , -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl) 2 and R c ; and R c is aryl, heteroaryl or heterocycle; wherein each R c is independently substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —SH, —S(alkyl), —SO 2 (alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl) 2 , —C(═O)OH, —C═O)Oalkyl, —C(═O)NH 2 , —C(═O)N(H)(alkyl), —C(═O)N(alkyl) 2 , haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH 2 , -alkyl-N(H)(alkyl), -alkyl-N(alkyl) 2 , -alkyl-N(H)C(═O)NH 2 , -alkyl-N(H)C(═O)N(H)(alkyl), -alkyl-N(H)C(═O)N(alkyl) 2 , -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl, -alkyl-C(═O)NH 2 , -alkyl —C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl) 2 . |
| Claim: | 15. The compound of claim 14 wherein R 1 is OH and R 2 is H. |
| Claim: | 16. The compound of claim 14 wherein R 1 is OH, R 2 is H, X is O and R 3 is alkyl, cycloalkenylalkyl, cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSR a , -alkylSOR a , -alkylSO 2 R a or -alkylNR a R b . |
| Claim: | 17. The compound of claim 14 wherein R 1 is OH, R 2 is H, X is O, R 3 is alkyl or cycloalkyl and R 4 is aryl or heteroaryl and R 4a and R 4b are each hydrogen. |
| Claim: | 18. The compound of claim 14 wherein R 1 is OH, R 2 is H, X is O, R 3 is alkyl or cycloalkylalkyl and R 4 is phenyl and R 4a and R 4b are each hydrogen. |
| Claim: | 19. The compound of claim 14 wherein R 1 is OH, R 2 is H, X is O, R 3 is alkyl or cycloalkylalkyl, R 4 is phenyl substituted with 0, 1, 2, 3 or 4 substituents selected from the group consisting of halo, —OR 4a and —NR 4a R 4b , and R 7 is alkyl; wherein R 4a and R 4b are independently selected from the group consisting of hydrogen and alkyl. |
| Claim: | 20. The compound of claim 14 or a pharmaceutically acceptable salt form, stereoisomer, ester, salt of an ester, or combination thereof, selected from the group consisting of (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)pentanamide; (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylbutanamide; (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)butanamide; (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide; (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylbutanamide; (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[({ethyl[(2-isopropyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]propanamide; (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylbutanamide; (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylbutanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)pentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)pentanamide; (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-tert-butoxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide; (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-tert-butoxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylpentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylpentanamide; (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]pentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]pentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-tert-butoxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-tert-butoxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(3-nitrobenzyl)amino]carbonyl}amino)pentanamide; methyl 4-{(5S,8S,9R)-8-benzyl-9-hydroxy-11-({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)-2,13-dimethyl-5-[(1S)-1-methylpropyl]-3,6-dioxo-2,4,7,11-tetraazatetradec-1-yl}-1,3-thiazol-2-ylcarbamate; (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylbutanamide; (2S,3S)-2-({[{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(3-pyridinylmethyl)amino]carbonyl}amino)pentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-({[methyl(4-pyridinylmethyl)amino]carbonyl}amino)pentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylpentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[6-(methoxymethyl)-2-pyridinyl]methyl}(methyl)amino]carbonyl}amino)-3-methylpentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl{amino)-3-methylpentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanamide; (2S,3S)-2-({[({6-[(Z)-amino(hydroxyimino)methyl]-2-pyridinyl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide; (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[6-(methoxymethyl)-2-pyridinyl]methyl}(methyl)amino]carbonyl}amino)-3,3-dimethylbutanamide; (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[6-(tert-butoxymethyl)-2-pyridinyl]methyl}(methyl)amino]carbonyl}amino)-3,3-dimethylbutanamide; (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide; (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide; (2S,3S)-2-({[(3-aminobenzyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide; (2S,3R)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-hydroxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide; (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide; (2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide; (2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide; (2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide; (2S,3S)-2-({[({2-[(1S)-1-aminoethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide; (2S,3S)-2-({[({2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide; (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[({6-[N-hydroxyethanimidoyl]-2-pyridinyl}methyl)(methyl)amino]carbonyl}amino)-3-methylpentanamide; and (2S,3S)-2-({[({2-[(1S)-1-(acetylamino)ethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide. |
| Claim: | 21. A pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of claim 1 , and a pharmaceutically acceptable carrier. |
| Claim: | 22. A pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of claim 1 , one, two, three, four, five or six agents selected from the group consisting of a second HIV protease inhibitor, a HIV reverse transcriptase inhibitor, an HIV entry/fusion inhibitor, an HIV integrase inhibitor and an HIV budding/maturation inhibitor, or combination thereof, and a pharmaceutically acceptable carrier. |
| Claim: | 23. The pharmaceutical composition of claim 22 wherein the second HIV protease inhibitor is selected from the group consisting of ritonavir, lopinavir, saquinavir, amprenavir, fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126, TMC-114, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649, KNI-272, DPC-681, DPC-684 and GW640385X. |
| Claim: | 24. The pharmaceutical composition of claim 22 wherein the HIV reverse transcriptase inhibitor is selected from the group consisting of lamivudine, stavudine, zidovudine, abacavir, zalcitabine, didanosine, tenofovir, emtricitabine, amdoxovir, elvucitabine, alovudine, MIV-210, Racivir (±-FTC), D-D4FC (Reverset, DPC-817), SPD754, nevirapine, delavirdine, efavirenz, capravirine, emivirine, calanolide A, GW5634, BMS-56190 (DPC-083), DPC-961, MIV-150, TMC-120 and TMC-125. |
| Claim: | 25. The pharmaceutical composition of claim 22 wherein the HIV entry/fusion inhibitor is selected from the group consisting of enfuvirtide (T-20), T-1249, PRO 2000, PRO 542, PRO 140, AMD-3100, BMS-806, FP21399, GW873140, Schering C(SCH-C), Schering D (SCH-D), TNX-355 and UK-427857. |
| Claim: | 26. The pharmaceutical composition of claim 22 wherein the HIV integrase inhibitor is selected from the group consisting of S-1360, zintevir (AR-177), L-870812 and L-870810. |
| Claim: | 27. The pharmaceutical composition of claim 22 wherein the HIV budding/maturation inhibitor is PA-457. |
| Claim: | 28. A method of inhibiting the replication of an HIV virus comprising contacting said virus with a therapeuctially effective amount of a compound or combination of compounds of claim 1 . |
| Claim: | 29. A method of treating an HIV infection comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound or combination of compounds of claim 1 . |
| Claim: | 30. A method of treating an HIV infection comprising administering to a patient in need of such treatment a pharmaceutical composition of claim 1 . |
| Claim: | 31. A method of inhibiting an HIV protease comprising contacting said HIV protease with a therapeutically effective amount of a compound or combination of compounds of claim 1 . |
| Current U.S. Class: | 514/601 |
| Patent References Cited: | 5914332 June 1999 Sham et al. 5977137 November 1999 Tung et al. 6060476 May 2000 Vazquez et al. 6150556 November 2000 Getman et al. 6251906 June 2001 Chen et al. 2002/0004503 January 2002 Sham et al. 2004/0039016 February 2004 Ghosh et al. 9405639 March 1994 9506030 March 1995 9533464 December 1995 9933792 July 1999 9933815 July 1999 0100635 January 2001 0206292 January 2002 0210124 February 2002 02092595 November 2002 03078438 September 2003 |
| Other References: | Li F, Goila-Gaur R, Salzwedel K, Kilgore NR, Reddick M, Matallana C, Castillo A, Zoumplis D, Martin DE, Orenstein JM, Allaway GP, Freed EO, Wild CT. PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc Natl Acad Sci U S A. Nov. 11, 2003;100(23):13555-60. Epub Oct. 22, 2003. cited by examiner Marcus U, Dittmar MT, Kräusslich HG.HIV: epidemiology and strategies for therapy and vaccination. Intervirology. 2002;45(4-6):260-6. cited by examiner van De Waterbeemd H, Smith DA, Beaumont K, and Walker DK, “Property-based design: optimization of drug absorption and pharmacokinetics,” Journal of Medicinal Chemistry, Apr. 2001,44(9), 1313-1333. cited by examiner Flynn D.L., et al., “Chemical Library Purification Strategies Based on Principles of Complementary Molecular Reactivity and Molecular Recognition,” 1997, vol. 119 (21), pp. 4874-4881. cited by applicant Riley G.P., et al., “Fosamprenavir Anti-HIV,” Drugs of the Future, 2001, vol. 26 (3), pp. 224-231. cited by applicant Vazquez M. L. et al., “Inhibitors of HIV-1 Protease Containing the Novel and Potent (R)-(Hydroxyethyosulfonamide Isostere,” Journal of Medicinal Chemistry, vol. 38 (4), pp. 581-584, 1995. cited by applicant Waterbeemd Van De H., et al., “Property-based Design: Optimization of Drug Absorption and Pharmacokinetics,” Journal of Medicinal Chemistry, 2001, vol. 44 (9), pp. 1313-1333. cited by applicant |
| Primary Examiner: | Zarek, Paul |
| Attorney, Agent or Firm: | Davis, Bradley E. |
| Accession Number: | edspgr.08653141 |
| Database: | USPTO Patent Grants |
| Language: | English |
|---|