CANNABINOID RECEPTOR MEDIATING COMPOUNDS

摘要

A compound, or a pharmaceutically acceptable salt or ester thereof, comprising (i) a CB1 receptor mediating scaffold and (ii) a second therapeutic scaffold.

主权项

1. A method for treating fibrosis, cirrhosis, or liver cancer in a subject, or reversing insulin resistance in a subject, comprising administering to the subject in need thereof, a therapeutically effective amount of a compound, or a tautomer thereof, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein A is an amidino-containing moiety, a hydrazino-containing moiety, R1, R2, and R3 are each independently selected from optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino; X is SO2 or C═O; R10, R11, R12, R13, and R20 are each independently selected from H, optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino; R21 is optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino; M is S or Se; a, b, and c are each independently 0, 1, 2, 3, 4 or 5; m, x, and y are each independently 0, 1, 2, 3, 4, 5 or 6; d is 0 or 1; and z is 1 or 2; or a structure of:wherein A is an amidino-containing moiety, a hydrazino-containing moiety, an optionally-substituted thiol,R1, R2, and R3 are each independently selected from optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino;
G and G′ are each independently H, hydroxy, optionally-substituted alkyl, aralkyl, amino, or optionally-substituted thiol; X is SO2 or C═O; R10, R11, R12, R13, and R20 are each independently selected from H, optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino; R21 is optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino; M is S or Se; a, b, and c are each independently 0, 1, 2, 3, 4 or 5; m, x, and y are each independently 0, 1, 2, 3, 4, 5 or 6; d is 0 or 1; and z is 1 or 2.