Inhibitors of fatty acid amide hydrolase

摘要

The present invention provides compounds, and pharmaceutically acceptable compositions thereof, encompassed by any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof. The present invention also provides methods for treating an FAAH mediated disease, disorder or condition by administering a therapeutically effective amount of a compound or composition comprising a compound of any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof, to a patient in need thereof. Additionally, the present invention provides methods for inhibiting FAAH by administering a therapeutically effective amount of a compound or composition comprising a compound of any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof, to a patient in need thereof.;

主权项

1. A compound of the following formula: or a pharmaceutically acceptable salt or prodrug thereof; wherein: (i) Z1 is —OH or —OR3 and Z2 is —OH, or —OR4, an optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C1-6 heteroalkyl, optionally substituted C2-6 heteroalkenyl, optionally substituted C2-6 heteroalkynyl, optionally substituted C6-10 aryl, or optionally substituted 5-10 membered heteroaryl; or (ii) Z1 is —OH or —OR3, and Z2 and wherein the ring is comprised of carbon atoms and optionally one or more additional heteroatoms independently selected from the group consisting of N, S and O taken together form an optionally substituted 5- to 7-membered ring; W3 is CR15; X is a covalent bond, —O—, —N═N—, —C═N—, —NR6—, —C(NR6)—, —S—, —C(O)—, —S(O)—, —S(O)2, or optionally substituted C1-6 alkylene, wherein one, two or three methylene units of the C1-6 alkylene are optionally and independently replaced with one or more groups selected from —O—, —N═N—, —C═N—, —NR6—, C(NR6)—, —S—, —C(O)—, —S(O)—, and —S(O)2—; each instance of R1 is, independently, halogen, —OR8, —CF3, —CN, —NO2, —SO2R8, —SOR8, —C(O)R8, —CO2R8, —C(O)N(R8)2, —CHO, —N3, —N2R8, —N(R8)2, —B(OH)2, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl; each instance of R2 is, independently, —OR9, —N(R9)2, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, or unsubstituted C6-10 aryl; each instance of R3 and R4 is, independently, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C1-6 heteroalkyl, optionally substituted C2-6 heteroalkenyl, optionally substituted C2-6 heteroalkynyl, optionally substituted C6-10 aryl, or optionally substituted 5-10 membered heteroaryl; each instance of R6, R8 and R9 is, independently, hydrogen, —SO2R11, —SOR11, —C(O)R11, —CO2R11, —C(O)N(R11)2, —C(O)NH(R11), —C(O)NH2, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6alkynyl, optionally substituted C1-6 heteroalkyl, optionally substituted C2-6heteroalkenyl, optionally substituted C2-6 heteroalkynyl, optionally substituted C3-10 carbocyclyl, optionally substituted 3-10 membered heterocyclyl, optionally substituted C6-10 aryl, or optionally substituted 5-10 membered heteroaryl; each instance of R11H is, independently, optionally substituted C1-6alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6alkynyl, optionally substituted C1-6 heteroalkyl, optionally substituted C2-6 heteroalkenyl, optionally substituted C2-6 heteroalkynyl, optionally substituted C3-10 carbocyclyl, optionally substituted 3-10 membered heterocyclyl, optionally substituted C6-10 aryl, or optionally substituted 5-10 membered heteroaryl; R15 is hydrogen, halogen, —CF3, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, or optionally substituted C2-6 alkynyl; n is 0, 1, 2 or 3; and with the proviso that the following compound is excluded: