NOVEL HETEROARYL AND HETEROCYCLE COMPOUNDS, COMPOSITIONS AND METHODS

摘要

Provided are novel heteroaryl and heterocycle compounds of formula (I-1), (I-2) or (I-3) and pharmaceutical compositions comprising them, uses and methods thereof for inhibiting the activity of PI3K and for treating inflammatory and autoimmune disorders diseases and cancer.;

主权项

1. A compound of formula I-1, I-2 or I-3: and/or its solvates, racemic mixture, enantiomers, diasteromers, tautomers, or mixtures of optional ratio, or pharmaceutically acceptable salts thereof, wherein:
Z═N or CH;R1 is hydrogen, optionally substituted C1-6 alkyl, optionally substituted C3-6 cycloalkyl, —(CR′ R″)n-heterocycle, —(CR′R″)n— aryl, —(CR′R″)n-heteroaryl, wherein heterocycle, aryl and heteroaryl independently are 5-6 membered monocyclic ring, optionally substituted with one or more groups selected from the group consisting of H, halo, optionally substituted C1-6 alkyl, optionally substituted C1-6 alkoxyl, —CN and —SO2R′;R2 and R3 are each independently hydrogen, optionally substituted C1-4 alkyl;R4 is hydrogen, halo, —CN, optionally substituted C1-6 alkyl, optionally substituted C3-6 cycloalkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, —C(O)NR′R″, optionally substituted 5-6 membered monocyclic heteroaryl;R5 is hydrogen and optionally substituted C1-4 alkyl;or R3, R5 and the atoms they are attached to form an optionally substituted 4-6 membered mono- or bicyclic saturated or partially unsaturated heterocyclic ring;R′ and R″ are each independently hydrogen, halo, optionally substituted C1-6 alkyl, optionally substituted C3-6 cycloalkyl or optionally substituted 4-6 membered monocyclic heterocycle;or R′, R″ and the nitrogen or carbon atom they are both attached to form an optionally substituted 3-7 membered heterocycle;each of m and n is 0, 1, 2, or 3;each of p is 1 or 2;W is a heteroaryl, which is optionally substituted with one or more groups selected from halo, —CN, —CF3, —NO2, —OR′, —NR′R″, —NR′COR″, —(CR′R″)n—C(O)R′, —(CR′R″)n—C(═N—OR′)—R″, —(CR′R″)n—C(O)NR′R″, —(CR′R″)n—S(O)pR′, —(CR′R″)n—SR′, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C1-6 alkoxy, optionally substituted 5-6 membered monocyclic heterocycle and optionally substituted 5-6 membered monocyclic heteroaryl;provided that for formula I-1, when Z═N, R3, R5 and the atoms they are attached to must form an optionally substituted 4-6 membered mono- or bicyclic saturated or partially unsaturated optionally substituted heterocyclic ring, and R4 is not hydrogen, —CN or aminomethyl.