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US 10,214,522 B2Granted
Anti-alphavbeta1 integrin inhibitors and methods of use
AssigneeThe Regents of the University of California
InventorsWilliam F. DeGrado, Dean Sheppard, Hyunil Jo, Nilgun Isik Reed, Youzhi Tang, Joel McIntosh
Life of this patent
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Abstract
Provided herein, inter alia, are methods and compositions for inhibiting αvβ1 integrin and for treating fibrosis.
Claims19
A method for treating fibrosis, said method comprising administering to a subject in need thereof an effective amount of a compound, or a salt thereof, having the formula:
- wherein,
- Ring A is 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 —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, or substituted or unsubstituted arylene;
- 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.
13 more elements
Dependencies are inferred from the claim text.