Indole and indoline derivatives and methods of use thereof

摘要

The present application relates to indole and indoline derivatives of formula (I), (II), (III), (IV), (V), or (VI);
wherein a, R1, R2, R3, R4, R5, U, V, W, X, Y, and Z are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

主权项

1. A compound of formula (IV): or a pharmaceutically acceptable salt thereof, wherein
a is a single or double bond;X is NR6;V is —CH2—;Y is CH2CH2—;Z is —CH2—;R1, R2, R3, and R4 are each independently hydrogen, alkyl, halogen, —OR1a, —S(O)2R2a, or haloalkyl;R1a is independently alkyl or haloalkyl;R2a, at each occurrence, is independently alkyl;R6 is —(CR4aR5a)m-G1 wherein R4a and R5a are each hydrogen, and m is 1 or 2, or R6 is —CR4a═CR5a-G1 wherein R4a and R5a are each hydrogen, and G1 is phenyl or pyridinyl, unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of alkyl, halogen, —OR1b, —N(Rb)(R3b), haloalkyl, heteroaryl, and heterocycle; wherein the heteroaryl is selected from the group consisting of furanyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, 1,2-oxazolyl, 1,3-oxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyridinyl, pyrazolyl, pyrrolyl, tetrazolyl, thiadiazolyl, 1,3-thiazolyl, thienyl, triazolyl, and triazinyl; wherein the heterocycle is selected from the group consisting of azetidinyl, azepanyl, aziridinyl, diazepanyl, 1,3-dioxanyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithianyl, imidazolinyl, imidazolidinyl, isothiazolinyl, isothiazolidinyl, isoxazolinyl, isoxazolidinyl, morpholinyl, oxadiazolinyl, oxadiazolidinyl, oxazolinyl, oxazolidinyl, piperazinyl, piperidinyl, pyranyl, pyrazolinyl, pyrazolidinyl, pyridazin-3(2H)-onyl, pyridin-2(1H)-onyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydropyrimidinyl, tetrahydrothienyl, thiadiazolinyl, thiadiazolidinyl, thiazolinyl, thiazolidinyl, thiomorpholinyl, 1,1-dioxidothiomorpholinyl, thiopyranyl, and trithianyl; wherein the heteroaryl and heterocycle are each independently unsubstituted or substituted with at least one alkyl;Rb and R1b, at each occurrence, are each independently alkyl; andR3b, at each occurrence, is independently alkoxyalkyl, or alkyl.