Substituted pyrazino[2,3-b]pyrazines as mTOR kinase inhibitors

摘要

Provided herein are Heteroaryl Compounds having the following structure:;wherein R1-R4 are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, neurodegenerative diseases, diabetes, obesity, neurological disorders, age-related diseases, or cardiovascular conditions, comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.;Furthermore, provided are methods of preparing a compound of formula (III),;;Furthermore, provided are methods of preparing a compound of formula (VI),;

主权项

1. A compound having formula (III): or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein: X is halogen, B(OR+)2 or Sn(R++)3; each R+ is independently hydrogen or substituted or unsubstituted C1-3 alkyl, or each R+, together with the boron atom and the atoms to which they are attached, form a cyclic boronate; each R++ is independently C1-4 alkyl; R2 is H, unsubstituted C1-8 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, or substituted or unsubstituted cycloalkylalkyl; and R3 and R4 are each independently H, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aralkyl, or substituted cycloalkylalkyl, wherein substituted means substituted with a substituent selected from the group consisting of chloro; iodo; bromo; fluoro; alkyl; hydroxy; alkoxy; alkoxyalkyl; amino; alkylamino; carboxy; nitro; cyano; thiol; thioether; imine; imide; amidine; guanidine; enamine; aminocarbonyl; acylamino; phosphonato; phosphine; thiocarbonyl; alkylsulfonyl; sulfonamide; acyl; ester; urea; urethane; oxime; hydroxylamine; alkoxyamine; aralkoxyamine; N-oxide; hydrazine; hydrazide; hydrazone; azide; isocyanate; isothiocyanate; cyanate; thiocyanate; oxo; B(OH)2, O(alkyl)aminocarbonyl; cycloalkyl, which may be monocyclic or fused or non-fused polycyclic, or a heterocyclyl, which may be monocyclic or fused or non-fused polycyclic; monocyclic or fused or non-fused polycyclic aryl or heteroaryl; aryloxy; aralkyloxy; heterocyclyloxy; and heterocyclylalkoxy.