ANTI-ALPHAVBETA1 INTEGRIN COMPOUNDS AND METHODS

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 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; L1 and L2 are independently a bond or substituted or unsubstituted C1-C10 alkylene; 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, or substituted or unsubstituted alkylarylene; X is a bond, —C—, —C—C—, —C═C—, —C—C—C—, —C═C—C—, —C—C═C—, —O—C—, —C—O—, —C—O—C, —S—C—, —C—S—, —C—S—C—; Y is a bond, —C(O)N(R4)—, —O—, —C(O)O—, —S—, —N(SO2—R4)—, —N(C(O)R4)—, —N(C(O)OR4)—, —(NR4)C(O)—, —N(R4)—, 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, oxo, —N3, —CF3, —CCl3, —CBr3, —CI3, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2Cl, —SO2CH3—SO3H, —OSO3H, —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, substituted or unsubstituted heteroaryl, or a detectable moiety; R2 is independently halogen, —N3, —CF3, —CCl3, —CI3, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2Cl, —SO2CH3—SO3H, —OSO3H, —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, substituted or unsubstituted heteroaryl, or a detectable moiety, or wherein if z2 an integer of 2 to 5, two R2 substituents attached to adjacent ring carbons are optionally joined to form a substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; R3A and R3B are independently hydrogen, —C(NH)NH2, —C(NH)R3D, —C(NR3C)NH2, —C(NR3C)R3D, —C(NCN)NH2, NH, 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, or R3A and R3B are optionally joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R3C and R3D are independently hydrogen, halogen, oxo, —N3, —CF3, —CCl3, —CI3, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2Cl, —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 independently hydrogen or unsubstituted C1-C5 alkyl; z1 is an integer from 1 to 9; and z2 is an integer from 1 to 5.