Modulators of opioid receptors and methods of use thereof

摘要

Provided herein are compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as pain, neurological disorders, psychiatric disorders, and neuromuscular disorders. Compounds provided herein modulate the activity of opioid receptor (e.g., μ-opioid receptor) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

主权项

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein R1 is heteroaryl which is optionally substituted; R2 is aryl which is optionally substituted; Z1 is ═O; Z2 is NR3R4; X is CR7R8; n is 1; R3 is (i) hydrogen; or (ii) alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which is optionally substituted; or (iii) R3 and R4 together with the nitrogen atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclyl or heteroaryl ring; or (iv) R4 is OH and R3 is hydrogen; R4 is (i) alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which is optionally substituted; or (ii) R3 and R4 together with the nitrogen atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclyl or heteroaryl ring; or (iii) R4 is OH and R3 is hydrogen; R7 and R8 are independently (i) hydrogen, halo, or cyano; or (ii) alkyl, alkenyl, heteroalkyl, alkoxyl, aminoalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which is optionally substituted; or (iii) OR3, C(O)OR3, —C(O)NH2, —C(O)NR3R4, or C(O)R3; or (iv) R7 and R8 together with the carbon atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclyl, heteroaryl, aryl, or cycloalkyl ring; and optionally R2 and R7 or R8 together with the atoms to which they are attached form an optionally substituted heterocyclyl or heteroaryl ring.