ANTI-ALPHAVBETA1 INTEGRIN INHIBITORS AND METHODS OF USE

摘要

Provided herein, inter alia, are methods and compositions for inhibiting αvβ1 integrin and for treating fibrosis.

主权项

1. A compound having the formula: wherein, Ring A is substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ring C is aryl or heteroaryl; L2 is independently a bond or substituted, unsubstituted C1-C10 alkylene, or unsubstituted 2 to 10 membered heteroalkylene; L3 is a bond, substituted or unsubstituted C1-C10 alkylene, substituted or unsubstituted 2 to 10 membered heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or substituted or unsubstituted alkylarylene; Y is a bond, —C(O)N(R4)—, —O—, —C(O)O—, —S—, —N(SO2R4)—, —N(C(O)R4)—, —N(C(O)OR4)—, —N(R4)C(O)—, —N(R4)—, —N(R4)C(O)NH—, —NHC(O)N(R4)—, —N(R4)C(O)O—, —C(O)—, —N(R4)CH2—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene; R1 is independently halogen, —N3, —CX3, —CHX2, —CH2X, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2CH3—SO3H, —OSO3H, —SO2NH2, —SO2Ph, —NHNH2, —ONH2, —NHC(O)NHNH2, —OPO3H, —PO3H2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a detectable moiety; R2 is —NR3AR3B, —C(NH)NH2, —C(NH)R3B, —C(NR3A)NH2, —C(NR3A)R3B, —C(NCN)NH2, —NH2, —C(NH)NHR3B, —C(NR3A)NHR3B, —C(NCN)NHR3B, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted fused ring cycloalkyl, substituted or unsubstituted fused ring heterocycloalkyl, substituted or unsubstituted fused ring aryl, or substituted or unsubstituted fused ring heteroaryl; R3A and R3B are independently hydrogen, —C(NH)NH2, —C(NH)R3D, —C(NR3C)NH2, —C(NR3C)R3D, —C(NCN)NH2, —NH2, —C(NH)NHR3D, —C(NR3C)NHR3D, —C(NCN)NHR3D, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, wherein R3A and R3B are optionally joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R3C is hydrogen, halogen, —N3, —CX1C3, —CHX1C2, —CH2X1C, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2CH3—SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R3D is hydrogen, halogen, —N3, —CX1D3, —CHX1D2, —CH2X1D, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2CH3—SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R4 is hydrogen or unsubstituted C1-C5 alkyl; R12 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or a prodrug moiety. each X, X1C and X1D is independently —F, —Cl, —Br, or —I; and z1 is an integer from 0 to 5.