Inhibitors of fatty acid amide hydrolase
AssigneeInfinity Pharmaceuticals, Inc.
InventorsAlfredo C. Castro, Catherine A. Evans, Louis Grenier, Michael J. Grogan
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Abstract
Provided herein are compounds of formula (I): or pharmaceutically acceptable salts, solvates or prodrugs thereof or mixtures thereof, wherein Z1, Z2, X1, X2, X3, R1, R2, R3, R4, m and n are defined herein. Also provided are pharmaceutically acceptable compositions that include a compound of formula I and a pharmaceutically acceptable excipient. Also provided are methods for treating an FAAH-mediated disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound or composition of the present invention.
Claims25
A compound of formula III:
- or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof, wherein:
- is selected from a single bond and a double bond;
- m is 1 when is a single bond;
- m is 0 when is a double bond;
- Z1 is —OR14;
- Z2 is —OR15;
- R1, R2, R3, R4, R6, R7, R12 and R13 each independently is selected from H, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 perhaloalkyl, —CN, —OR16, NR17R18, —C(O)R19, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
- R8 is selected from C2-6 alkenyl, C2-6 alkynyl, —C(O)R20, —C(O)NR22R23, S(O)2R24, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —(CH2)p—R25;
- R14 and R15, at each occurrence, each independently is selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
- R16, at each occurrence, each independently is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
- R17 and R18, at each occurrence, each independently is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C(O)R26, —C(O)OR27, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
- R19, at each occurrence, each independently is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
- R20 is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —(CH2)q—R28;
- R22 and R23 each independently is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —(CH2)r—R29;
- R24 is selected from C1-6 alkyl, C2-6 alkenyl, alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —(CH2)t—R30;
- R25 is selected from C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
- R26 and R27 each independently is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
- R28, R29, and R30, at each occurrence, each independently is selected from —OR31, —NR32R33, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
- R31, R32 and R33, at each occurrence, each independently is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
- and
- p, q, r, and t, at each occurrence, each independently is selected from 1, 2, 3, 4, 5 and 6.
Dependencies are inferred from the claim text.