Azetidinone Derivatives and Methods of Use Thereof

A compound having the formula:

• or a pharmaceutically acceptable salt, solvate, ester, prodrug or stereoisomer thereof, wherein:
• R1 is H, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkylalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or -alkylene-C(O)N(alkyl)2, wherein an alkyl or aryl group may be optionally and independently substituted with one or more of the following groups:
• —(C═N—O-alkyl)CH3, —NC(O)NH2, —NC(O)NH(alkyl), —NC(O)N(alkyl)2, —SO2NH2, —SO2NH(alkyl), —SO2N(alkyl)2, —CF3, —OH, -halo, —CN, -alkoxy, —C(O)O-alkyl, —C(O)N(R6)2, —S(O)alkyl, —SO2-alkyl, or —P(O)(O-alkyl)2, an aryl group may further be optionally and independently substituted with one or more alkyl groups, and an alkyl group may further be optionally and independently substituted with one or more aryl groups;
• R2 is H, alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, R6-A-, alkyl-O—C(O)—, (alkyl)2-N-alkylene-C(O)—, CN-alkylene-C(O)—, alkyl-O-alkylene-C(O)—, alkyl-C(O)-alkylene-C(O)—, alkyl-NH—C(O)— or alkyl-O—C(O)-alkylene-C(O)—, wherein an alkyl or aryl group may be optionally and independently substituted with one or more of the following groups:
• —(C═N—O-alkyl)CH3, —NC(O)NH2, —NC(O)NH(alkyl), —NC(O)N(alkyl)2, —SO2NH2, —SO2NH(alkyl), —SO2N(alkyl)2, —CF3, —OH, -halo, —CN, -alkoxy, —C(O)O-alkyl, —S(O)alkyl, —SO2-alkyl, or —P(O)(O-alkyl)2, and an aryl group may further be optionally and independently substituted with one or more alkyl groups;
• R3 is H, alkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, —NH-arylalkyl, aralkoxy, cycloalkyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl, wherein an alkyl or aryl group can be optionally and independently substituted with one or more of the following groups:
• —(C═N—O-alkyl)CH3, —NH—C(O)NH-alkyl, —C(O)NH2, —CN, —C(O)NH-alkyl, —C(O)O-alkyl, —C(O)H, —C(O)OH, —NC(O)NH2, —NC(O)NH(alkyl), —NC(O)N(alkyl)2, —SO2NH2, —SO2NH(alkyl), —SO2N(alkyl)2, —CF3, —OH, -halo, —CN, -alkoxy, —C(O)O-alkyl, —S(O)alkyl, —SO2-alkyl, or —P(O)(O-alkyl)2, an aryl group can be optionally and independently substituted with one or more alkyl groups, and a heteroaryl group can be optionally and independently substituted with one or more aryl or heteroaryl groups;
• each occurrence of R4 and R5 is independently —C(R7)2—, wherein the ring carbon atom of one R4 group and the ring carbon atom of one R5 group may optionally be joined by a —CH2—CH2— group;
• each occurrence of R6 is independently alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, benzofused cycloalkyl, benzofused heterocycloalkyl or benzofused heterocycloalkenyl;
• each occurrence of R7 is independently H, alkyl, —CN, or —OH;
• A is —C(O)—, —OC(O)—, —NHC(O)—, -alkylene-C(O)—, —O-alkylene-C(O)—, —C(O)-alkylene-C(O)—, —C(O)—CH2—NHC(O)—, -alkylene-, -alkenylene-, -alkenylene-C(O)—,
• -alkylene-NHC(O)—, wherein an A group is joined to the nitrogen atom to which it is attached via a terminal C(O) group;
• u is an integer ranging from 0 to 3;
• and
• v is an integer ranging from 0 to 3;
• such that the sum of u and v is from 3 to 5,
• such that the compound of formula (II) is not a compound of formula (IA), (IB), (IC) or (ID) as set forth in the above specification.

A compound having the formula:

• or a pharmaceutically acceptable salt, solvate, ester, prodrug or stereoisomer thereof wherein:
• R1 is alkyl, aryl, cycloalkyl, —CH2-cycloalkyl, —CH2-aryl, —CH(aryl)2, heteroaryl, wherein an aryl group may be optionally substituted with up to 3 substituents independently selected from alkyl, halo, —NO2, —O-alkyl, —CN, —C(O)O-alkyl, —CF3, —C(O)-alkyl or —S(O)2-alkyl;
• R2 is H, —C(O)aryl, —C(O)NH-alkyl, —C(O)NH-alkylene-aryl, —C(O)NR6-aryl, —C(O)NH-cycloalkyl, —C(O)NH—CH2-aryl, —C(O)NH-heteroaryl, —C(O)NH-heterocycloalkyl, —C(O)NH-benzofused heterocycloalkyl, —C(O)O-alkyl or
• wherein an alkyl group may be optionally substituted with up to 2 substituents independently selected from —OH, —O-alkyl, —C(O)OR6 or —C(O)N(R6)2;
• an aryl group may be optionally substituted with up to 3 substituents independently selected from alkyl, —O-alkyl, -halo, unsubstituted alkyl, —CN or —CF3;
• and a cycloalkyl group may be may be optionally and independently substituted with up to 3 unsubstituted alkyl groups;
• R3 is H, aryl or heteroaryl, wherein an aryl group or may be optionally substituted with up to 2 substituents independently selected from alkyl, halo, —OH, or —O-benzyl;
• each occurrence of R4 and R5 is independently —CH(R7)—, wherein the ring carbon atom of one R4 group and the ring carbon atom of one R5 group may optionally be joined by a —CH2—CH2— group;
• each occurrence of R6 is H or alkyl;
• each occurrence of R7 is independently H, alkyl, —CN, or —OH;
• A is —CH2— or —C(O)—;
• u and v are each 2;
• and
• w is an integer ranging from 1 to 3,
• such that the compound of formula (III) is not a compound of formula (IA), (IB), (IC) or (ID) as set forth in Tables 1-4 in the above specification.