Therapeutic compounds and related methods of use

摘要

Compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat a disorder, e.g., schizophrenia and cognitive deficit, in a subject are described herein. The compounds disclosed herein include quinoline and quinazoline-containing compounds that modulate striatal-enriched tyrosine phosphatase (STEP) activity.

主权项

1. A compound of formula (I): or a salt thereof, wherein: A is CH or N; B is phenyl, dihydroindenyl, dihydrobenzoxazinyl, dihydrobenzodioxinyl, chromenyl, tetrahydroisoquinolyl, tetrahydroquinolinyl, dihydroquinolyl, quinolyl, tetrahydroquinazolinyl, indolinyl, dihydrobenzothiazolyl, dihydrobenzimidazolyl, dihydrobenzoxazolyl, isoindolinyl, benzofuryl, benzothienyl, benzodioxolyl, indolyl, indazolyl, benzoimidazolyl, benzotriazolyl, benzisoxazolyl, benzoxazolyl, benzothiazolyl, benzoxadiazolyl, tetrahydrobenzothienyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, thiadiazolyl or pyridyl; m is 0, 1, 2, 3, or 4; E is phenyl, thienyl, or pyrrolyl; when E is phenyl, n is 1 or 2; and when E is thienyl or pyrrolyl, n is 0 or 1; L is NR5; one of X and Z is N and the other is CH; p is 0, 1, or 2; each R1 is independently C1-C8 alkyl, halo, haloalkyl, haloalkoxy, alkoxyalkyl, —CN, oxo, —NO2, —C(Y)NRbRb′, —NRcC(Y)Rc′, —SO2NRbRb′, —ORd, or —S(O)qRf; each R2 is independently C1-C8 alkyl, C3-C8 cycloalkyl, thiomorpholinylalkyl, pyrrolidinylalkyl, morpholinylalkyl, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, hydroxyalkyl, alkoxyalkyl, silyloxyalkyl, —CN, —NO2, —C(O)ORa, —C(Y)NRbRb′, —NRbRb′, —ORd, —C(Y)Re or —S(O)qRf; each R3 is independently C1-C8 alkyl, halo, haloalkyl, —NRbRb′ or —ORd; R5 is hydrogen; or when m is not 0, R5 and one R1 may be taken together with the atoms to which they are attached to form an optionally substituted heteroaryl or heterocyclyl ring; Y is O or S; q is 1 or 2; and each Ra, Rb, Rb′, Rc, Rc′, Rd, Re, and Rf is independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, phenyl, dihydroindenyl, morpholinyl, tetrahydropyranyl, piperidyl, pyrrolidinyl, thiomorpholinyl, phenylalkyl, thienylalkyl, pyridylalkyl, tetrahydropyranylalkyl, dihydroindenylalkyl, tetrahydrofurylalkyl, hydroxyalkyl, morpholinylalkyl, pyrrolidinylalkyl, dialkylaminoalkyl, piperidylalkyl, benzodioxolilalkyl, dihydrobenzodioxinylalkyl, C3-C8 cycloalkylalkyl, haloalkyl or alkoxyalkyl.