HIV protease inhibiting compounds
View Patent ↗A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
1. A compound having formula (III)
or a pharmaceutically acceptable salt form or a stereoisomer thereof, wherein:
B is H or —CH 2 R 9 ;
L is —C(═O), —C(═S), —C(═NH) or —S(O) 2 ;
R 1 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 1 is substituted with 0, 1 or 2 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), -alkylC(O)N(alkyl) 2 , and R 1a ;
R 1a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 1a 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 -alkylC(O)N(alkyl) 2 ;
R 2 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 2 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, —OR a , —SR a , —SOR a , —SO 2 R a , —NR a R b , —NR b C(O)R a —N(R b )C(O)OR a , —N(R a )C(═N)NR a R b , —N(R a )C(O)NR a R b , —C(O)NR a R b , —C(O)OR a and R 2a ;
R 2a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 2a 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 3 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, -alkylOR a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylNR a R b , -alkylN(R b )C(O)R a , -alkylN(R b )C(O)OR a , -alkylN(R a )C(═N)NR a R b , -alkylN(R a )C(O)NR a R b , -alkylC(O)NR a R b , -alkylC(O)OR a , cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocycle, heterocyclealkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkyl moiety of the cycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl, heterocycle moiety of the heterocyclealkyl, heteroaryl moiety of the heteroarylalkyl and the aryl moiety of the arylalkyl are independently 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), -alkylC(O)N(alkyl) 2 and R 3a ;
R 3a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 3a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, oxo, alkyl, alkenyl, 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 -alkylC(O)N(alkyl) 2 ;
R 4 is H and R 5 is OR 16 ;
R 6 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, -alkylOR a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylNR a R b , -alkylN(R b )C(O)R a , -alkylN(R b )C(O)OR a , -alkylN(R a )C(═N)NR a R b , -alkylN(R a )C(O)NR a R b , -alkylC(O)NR a R b , -alkylC(O)OR a , cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocycle, heterocyclealkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkyl moiety of the cycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl, heterocycle moiety of the heterocyclealkyl, heteroaryl moiety of the heteroarylalkyl and the aryl moiety of the arylalkyl are independently 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), -alkylC(O)N(alkyl) 2 and R 6a ;
R 6a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 6a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, oxo, alkyl, alkenyl, 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 -alkylC(O)N(alkyl) 2 ;
R 7 is —N(R b )C(O)OR a , alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl are independently substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, —OR a , —OC(O)R a , —SR a , —SOR a , —SO 2 R a , —NR a R b , —N(R b )C(O)R a , —N(R b )C(O)OR a , —N(R a )C(═N)NR a R b , —N(R a )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 9 is alkyl, alkenyl, alkynyl, 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, formyl, halo, nitro, oxo, —OR a , —SR a , —SOR a , —SO 2 R a ,—SO 2 NR a , —SO 2 OR a , —NR a R b , —N(R b )C(O)R a , —N(R b )SO 2 R a , —N(R b )SO 2 NR a R b , —N(R b )C(O)NR a R b , —N(R b )C(O)OR a , —C(O)R a , —C(O)NR a R b , —C(O)OR a , haloalkyl, nitroalkyl, cynaoalkyl, formylalkyl, -alkylOR a , -alkyl-O—P(O)(OR a )(OR a ), -alkylNR a R b , -alkylN(R b )C(O)OR a , -alkylN(R b )SO 2 NR a R b , -alkylN(R b )C(O)R a , -alkylN(R b )C(O)NR a R b , -alkylN(R b )SO 2 R a , -alkylC(O)OR a , -alkylC(O)R 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, 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 16 is hydrogen or R 15 ;
R 15 is
R 103 is C(R 105 ) 2 , O or —N(R 105 );
R 104 is hydrogen, alkyl, haloalkyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl,
each M is independently selected from the group consisting of H, —N(R 105 ) 2 , alkyl, alkenyl, and R 106 ; wherein 1 to 4 —CH 2 radicals of the alkyl or alkenyl, other than the —CH 2 radical that is bound to Z, is optionally replaced by a heteroatom group selected from the group consisting of O, S, S(O), SO 2 and N(R 105 ); and wherein any hydrogen in said alkyl, alkenyl or R 106 is optionally replaced with a substituent selected from the group consisting of oxo, —OR 105 , —R 105 , —N(R 105 ) 2 , —CN, —C(O)OR 105 , —C(O)N(R 105 ) 2 , —SO 2 N(R 105 ), —N(R 105 )C(O)R 105 , —C(O)R 105 , —SR 105 , —S(O)R 105 , —SO 2 R 105 , —OCF 3 , —SR 106 , —SOR 106 , —SO 2 R 106 , —N(R 105 )SO 2 R 105 , halo, —CF 3 , NO 2 and phenyl; provided that when M is —N(R 105 ) 2 , Z 1 and Z 2 are —CH 2 ;
Z 1 is CH 2 , O, S, —N(R 105 ), or, when M is absent, H;
Z 2 is CH 2 , O, S or —N(R 105 );
Q is O or S;
W is P or S; wherein when W is S, Z 1 and Z 2 are not S;
M′ is H, alkyl, alkenyl or R 106 ; wherein 1 to 4 —CH 2 radicals of the alkyl or alkenyl is optionally replaced by a heteroatom group selected from O, S, S(O), SO 2 , or N(R 105 ); and wherein any hydrogen in said alkyl, alkenyl or R 106 is optionally replaced with a substituent selected from the group consisting of oxo, —OR 105 , —R 105 , —N(R 105 ) 2 , —CN, —C(O)OR 105 , —C(O)N(R 105 ) 2 , —SO 2 N(R 105 ), —N(R 105 )C(O)R 105 , —C(O)R 105 , —SR 105 , —S(O)R 105 , —SO 2 R 105 , —OCF 3 , —SR 106 , —SOR 106 , —SO 2 R 106 , —N(R 105 )SO 2 R 105 , halo, —CF 3 and NO 2 ;
R 106 is a monocyclic or bicyclic ring system selected from the group consisting of aryl, cycloalkyl, cycloalkenyl heteroaryl and heterocycle; wherein any of said heteroaryl and heterocycle ring systems contains one or more heteroatoms selected from the group consisting of O, N, S, SO, SO 2 and N(R 105 ); and wherein any of said ring system is substituted with 0, 1, 2, 3, 4, 5 or 6 substituents selected from the group consisting of hydroxy, alkyl, alkoxy, and —OC(O)alkyl;
each R 105 is independently selected from the group consisting of H or alkyl; wherein said alkyl is optionally substituted with a ring system selected from the group consisting of aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocycle; wherein any of said heteroaryl and heterocycle ring systems contains one or more heteroatoms selected from the group consisting of O, N, S, SO, SO 2 , and N(R 105 ); and wherein any one of said ring systems is substituted with 0, 1, 2, 3 or 4 substituents selected from the group consisting of oxo, —OR 105 , —R 105 , —N(R 105 ) 2 , —N(R 105 )C(O)R 105 , —CN, —C(O)OR 105 , —C(O)N(R 105 ) 2 , halo and —CF 3 ;
each R 107 and R 108 are independently selected from the group consisting of hydrogen and alkyl;
q is 0 or 1;
m is 0 or 1;
m′ is 0 or 1;
m″ is 0 or 1;
r is 0, 1, 2, 3 or 4;
t is 0 or 1;
R a and R b at each occurrence are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and 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 cyano, nitro, halo, oxo, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, —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), -alkylC(O)N(alkyl) 2 and R c ;
alternatively, R a and R b , together with the nitrogen atom to which they are attached, form a ring selected from the group consisting of heteroaryl and heterocycle; wherein each of the heteroaryl and heterocycle 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 ;
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, -alkyl-NH 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.
2. A compound having formula (III)
or a pharmaceutically acceptable salt form or a stereoisomer thereof, wherein:
B is H or —CH 2 R 9 ;
L is —C(═O), —C(═S), —C(═NH) or —S(O) 2 ;
R 1 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 1 is substituted with 0, 1 or 2 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), -alkylC(O)N(alkyl) 2 , and R 1a ;
R 1a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 1a 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 -alkylC(O)N(alkyl) 2 ;
R 2 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 2 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, —OR a , —SR a , —SOR a , —SO 2 R a , —NR a R b , —NR b C(O)R a —N(R b )C(O)OR a , —N(R a )C(═N)NR a R b , —N(R a )C(O)NR a R b , —C(O)NR a R b , —C(O)OR a and R 2a ;
R 2a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 2a 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 3 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, -alkylOR a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylNR a R b , -alkylN(R b )C(O)R a , -alkylN(R b )C(O)OR a , -alkylN(R a )C(═N)NR a R b , -alkylN(R a )C(O)NR a R b , -alkylC(O)NR a R b , -alkylC(O)OR a , cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocycle, heterocyclealkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkyl moiety of the cycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl, heterocycle moiety of the heterocyclealkyl, heteroaryl moiety of the heteroarylalkyl and the aryl moiety of the arylalkyl are independently 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), -alkylC(O)N(alkyl) 2 and R 3a ;
R 3a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 3a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, oxo, alkyl, alkenyl, 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 -alkylC(O)N(alkyl) 2 ;
R 5 is H and R 4 is OR 16 ;
R 6 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, -alkylOR a , -alkylSR a , -alkylSOR a , -alkylSO 2 R a , -alkylNR a R b , -alkylN(R b )C(O)R a , -alkylN(R b )C(O)OR a , -alkylN(R a )C(═N)NR a R b , -alkylN(R a )C(O)NR a R b , -alkylC(O)NR a R b , -alkylC(O)OR a , cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocycle, heterocyclealkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkyl moiety of the cycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl, heterocycle moiety of the heterocyclealkyl, heteroaryl moiety of the heteroarylalkyl and the aryl moiety of the arylalkyl are independently 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), -alkylC(O)N(alkyl) 2 and R 6a ;
R 6a is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein each R 6a is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, oxo, alkyl, alkenyl, 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 -alkylC(O)N(alkyl) 2 ;
R 7 is —N(R b )C(O)OR a , alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl are independently substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, —OR a , —OC(O)R a , —SR a , —SOR a , —SO 2 R a , —NR a R b , —N(R b )C(O)R a , —N(R b )C(O)OR a , —N(R a )C(═N)NR a R b , —N(R a )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)0alkyl, -alkylC(O)NH 2 , -alkylC(O)N(H)(alkyl) and -alkyl-C(O)N(alkyl) 2 ;
R 9 is alkyl, alkenyl, alkynyl, 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, formyl, halo, nitro, oxo, —OR a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a , —SO 2 OR a , —NR a R b , —N(R b )C(O)R a , —N(R b )SO 2 R a , —N(R b )SO 2 NR a R b , —N(R b )C(O)NR a R b , —N(R b )C(O)OR a , —C(O)R a , —C(O)NR a R b , —C(O)OR a , haloalkyl, nitroalkyl, cynaoalkyl, formylalkyl, -alkylOR a , -alkyl-O—P(O)(OR a )(OR a ), -alkylNR a R b , -alkylN(R b )C(O)OR a , -alkylN(R b )SO 2 NR a R b , -alkylN(R b )C(O)R a , -alkylN(R b )C(O)NR a R b , -alkylN(R b )SO 2 R a , -alkylC(O)OR a , -alkylC(O)R 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, 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 16 is hydrogen or R 15 ;
R 15 is
R 103 is C(R 105 ) 2 , O or —N(R 105 );
R 104 is hydrogen, alkyl, haloalkyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl,
each M is independently selected from the group consisting of H, —N(R 105 ) 2 , alkyl, alkenyl, and R 106 ; wherein 1 to 4 —CH 2 radicals of the alkyl or alkenyl, other than the —CH 2 radical that is bound to Z, is optionally replaced by a heteroatom group selected from the group consisting of O, S, S(O), SO 2 and N(R 105 ); and wherein any hydrogen in said alkyl, alkenyl or R 106 is optionally replaced with a substituent selected from the group consisting of oxo, —OR 105 , —R 105 , —N(R 105 ) 2 , —CN, —C(O)OR 105 , —C(O)N(R 105 ) 2 , —SO 2 N(R 105 ), —N(R 105 )C(O)R 105 , —C(O)R 105 , —SR 105 , —S(O)R 105 , —SO 2 R 105 , —OCF 3 , —SR 106 , —SOR 106 , —SO 2 R 106 , —N(R 105 )SO 2 R 105 , halo, —CF 3 , NO 2 and phenyl; provided that when M is —N(R 105 ) 2 , Z 1 and Z 2 are —CH 2 ;
Z 1 is CH 2 , O, S, —N(R 105 ), or, when M is absent, H;
Z 2 is CH 2 , O, S or —N(R 105 );
Q is O or S;
W is P or S; wherein when W is S, Z 1 and Z 2 are not S;
M′ is H, alkyl, alkenyl or R 106 ; wherein 1 to 4 —CH 2 radicals of the alkyl or alkenyl is optionally replaced by a heteroatom group selected from O, S, S(O), SO 2 , or N(R 105 ); and wherein any hydrogen in said alkyl, alkenyl or R 106 is optionally replaced with a substituent selected from the group consisting of oxo, —OR 105 , —R 105 , —N(R 105 ) 2 , —CN, —C(O)OR 105 , —C(O)N(R 105 ) 2 , —SO 2 N(R 105 ), —N(R 105 )C(O)R 105 , —C(O)R 105 , —SR 105 , —S(O)R 105 , —SO 2 R 105 , —OCF 3 , —SR 106 , —SOR 106 , —SO 2 R 106 , —N(R 105 )SO 2 R 105 , halo, —CF 3 and NO 2 ;
R 106 is a monocyclic or bicyclic ring system selected from the group consisting of aryl, cycloalkyl, cycloalkenyl heteroaryl and heterocycle; wherein any of said heteroaryl and heterocycle ring systems contains one or more heteroatoms selected from the group consisting of O, N, S, SO, SO 2 and N(R 105 ); and wherein any of said ring system is substituted with 0, 1, 2, 3, 4, 5 or 6 substituents selected from the group consisting of hydroxy, alkyl, alkoxy, and —OC(O)alkyl;
each R 105 is independently selected from the group consisting of H or alkyl; wherein said alkyl is optionally substituted with a ring system selected from the group consisting of aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocycle; wherein any of said heteroaryl and heterocycle ring systems contains one or more heteroatoms selected from the group consisting of O, N, S, SO, SO 2 , and N(R 105 ); and wherein any one of said ring systems is substituted with 0, 1, 2, 3 or 4 substituents selected from the group consisting of oxo, —OR 105 , —R 105 , —N(R 105 ) 2 , —N(R 105 )C(O)R 105 , —CN, —C(O)OR 105 , —C(O)N(R 105 ) 2 , halo and —CF 3 ;
each R 107 and R 108 are independently selected from the group consisting of hydrogen and alkyl;
q is 0 or 1;
m is 0 or 1;
m′ is 0 or 1;
m″ is 0 or 1;
r is 0, 1, 2, 3 or 4;
t is 0 or 1;
R a and R b at each occurrence are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and 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 cyano, nitro, halo, oxo, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, —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), -alkylC(O)N(alkyl) 2 and R c ;
alternatively, R a and R b , together with the nitrogen atom to which they are attached, form a ring selected from the group consisting of heteroaryl and heterocycle; wherein each of the heteroaryl and heterocycle 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 ;
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, -alkyl-NH 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.
3. The compound of claim 1 wherein, L is —C(═O) or —C(═S) and R 2 is alkyl.
4. The compound of claim 2 wherein, L is —C(═O) or —C(═S) and R 2 is alkyl.
5. The compound of claim 1 wherein L is —C(═O) or —C(═S), R 2 is alkyl, R 3 is arylalkyl wherein the aryl moiety of the arylalkyl is substituted with 0 or one R 3a , and R 3a is aryl or heteroaryl.
6. The compound of claim 2 wherein L is —C(═O) or —C(═S), R 2 is alkyl, R 3 is arylalkyl wherein the aryl moiety of the arylalkyl is substituted with 0 or one R 3a , and R 3a is aryl or heteroaryl.
7. The compound of claim 1 wherein L is —C(═O) or —C(═S), R 2 is alkyl, R 3 is arylalkyl wherein the aryl moiety of the arylalkyl is substituted with 0 or one R 3a wherein R 3a is aryl or heteroaryl and R 9 is aryl or heteroaryl.
8. The compound of claim 2 wherein L is —C(═O) or —C(═S), R 2 is alkyl, R 3 is arylalkyl wherein the aryl moiety of the arylalkyl is substituted with 0 or one R 3a wherein R 3a is aryl or heteroaryl and R 9 is aryl or heteroaryl.
9. A pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds, or a pharmaceutically acceptable salt form or stereoisomer thereof, and a pharmaceutically acceptable carrier, wherein the compound, or at least one of said compounds, is selected from the group consisting of
methyl(1S)-1-[({(1R,3S,4S)-3-hydroxy-4-{[(2S)-2-(3-{[6-(1-hydroxy-l-methylethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanoyl]amino}-5-phenyl-1[4-(2-pyridinyl) benzyl]pentyl}amino)carbony1]-2,2-dimethylpropylcarbamate, and
methyl(1S )-1-[({(1S,3S,4S)-4-{[(2S)-2-(3-benzyl -2-oxo-1-imidazolidinyl)-3,3-dimethylbutanoyl]amino }-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl) benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate.