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US 2018/0022706 A1Published application
Cannabinoid receptor mediating compounds
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsGeorge Kunos, Malliga Iyer, Resat Cinar, Kenner C. Rice
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Abstract
A compound, or a pharmaceutically acceptable salt or ester thereof, comprising (i) a CB1 receptor mediating scaffold conjugated to (ii) a second therapeutic scaffold.
Claims20
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 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.
8 more elements
A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:
- wherein R14 is 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.
A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:
- wherein A is —NH—C(═NH)—CH3 or —NH—C(═NH)—NH—C(═O)—CH3;
- and
- R′ is Cl or CF3.
A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:
- wherein 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;
- a, b, and c are each independently 0, 1, 2, 3, 4 or 5;
- and
- A is an amidino-containing moiety having a structure of
- wherein R4 is selected from H, optionally-substituted alkyl, optionally-substituted cycloalkyl, optionally-substituted heterocycloalkyl, 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;
- and
- R5 is a thiol substituted with an alkyl, a thiol substituted with a substituted alkyl, or an amino of the formula —NR30R31, where R30 and R31 are independently, hydrogen or an optionally-substituted alkyl, provided that at least one of R30 and R31 is optionally substituted alkyl.
5 more elements
A compound, or a pharmaceutically acceptable salt or ester thereof, having 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, provided that at least one of G or G′ is 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.
9 more elements
Dependencies are inferred from the claim text.