CYCLIC PEPTIDES AND USE AS MEDICINES

摘要

The present invention provides a compound of formula I;;;or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, and A-B are as defined herein, which are non-immunosuppressive, cyclophilin-binding, mPTP blockers and are therefore useful for the prevention or treatment of diseases or disorders such as HCV infection, stroke, multiple sclerosis, HBV infection, HPV infection, asthma, cancer, muscular dystrophy, sepsis, ischemia/reperfusion injury, and heart failure.

主权项

1. A compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein
A-B is —CH═CH or CH2CH2; R1 is C1-C4alkoxy or C1-C4 alkyl; R2 is —OR1a, or a 4 to 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, wherein said heterocycle is optionally substituted with at least one substituent selected from the group consisting of halogen, —OH, CN, —O(C1-C4)alkyl, oxo (═O), —S(O)2(C1-C4)alkyl, —C(O)(C1-C4)alkyl, —C(O)2(C1-C4)alkyl, C1-C4haloalkyl, C3-C7cycloalkyl, and C1-C4 alkyl optionally substituted with C1-C4alkoxy; R1a is C1-C4alkyl, (C1-C4)alkyl-OH, (C1-C4)alkyl-C1-C4alkoxy, (C2-C4)alkyl-NR9R10, a 4 to 8 membered heterocycle containing 1 to 3 heteroatom selected from N, S, and O, or a (C1-C4)alkyl-4 to 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, wherein said heterocycles are optionally substituted with at least one substituent selected from the group consisting of halogen, —OH, CN, —O(C1-C4)alkyl, oxo (═O), —S(O)2(C1-C4)alkyl, —C(O)(C1-C4)alkyl, —C(O)2(C1-C4)alkyl, C1-C4haloalkyl, C3-C7cycloalkyl, and C1-C4 alkyl optionally substituted with C1-C4alkoxy; R3 is C1-C6alkyl optionally substituted with at least one substituent selected from the group consisting of OH, O(C1-C4alkyl), —NR7R8, and S(C1-C6 alkyl); R4 is C1-C4 alkyl; R5 is H, (C1-C6)alkyl; R7 is H or C1-C4 alkyl; R8 is H or C1-C4 alkyl; or R7 and R8 taken together with the nitrogen to which they are attached form a 4 to 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, wherein said heterocycle is optionally substituted with at least one substituent selected from the group consisting of halogen and C1-C4 alkyl; R9 is H, C1-C4alkyl optionally substituted with one or more halogen, one or more hydroxy, C1-C4alkoxy, 5 to 6 membered heteroaryl or 5 to 6 membered heterocycle; and R10 is H, C1-C4alkyl optionally substituted with one or more halogen, C1-C4alkoxy or one or more hydroxy.