HIGH AFFINITY LIGANDS FOR NOCICEPTIN RECEPTOR ORL-1

摘要

Compounds of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein: the dotted line represents an optional double bond; X<1> is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl; X<2> is -CHO, -CN, optionally substituted amino, alkyl, or aryl; or X<1> is optionally substituted benzofused heterocyclyl and X<2> is hydrogen; or X<1> and X<2> together form an optionally benzofused spiro heterocyclyl group; R<1>, R<2>, R<3> and R<4> are independently H and alkyl, or (R<1> and R<4>) or (R<2> and R<3>) or (R<1> and R<3>) or (R<2> and R<4>) together can form an alkylene bridge of 1 to 3 carbon atoms; Z<1> is optionally substituted alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, or -CO2(alkyl or substituted amino) or CN; Z<2> is H or Z<1>; Z<3> is H or alkyl; or Z<1>, Z<2> and Z<3>, together with the carbon to which they are attached, form bicyclic saturated or unsaturated rings; pharmaceutical compositions therefore, and the use of said compounds as nociceptin receptor inhibitors useful in the treatment of pain, anxiety, cough, asthma, depression and alcohol abuse are disclosed.