ANALOGUES OF CORTISTATIN, THEIR SYNTHESIS AND APPLICATIONS

摘要

This document presents the compounds of formulas (A), (B), (C), (D) and (E), their pharmaceutically acceptable salts, quaternary amine salts and N-oxides, as well as their pharmaceutical compositions. Considered compounds of formulas (A ), (B), (C), (D), and (E) are useful as therapeutic agents for treating a wide range of conditions, for example, including, but not limited to, conditions associated with angiogenesis and the activity of CDK8 and / or CDK19 kinases. In addition, methods are provided for inhibiting the activity of CDK8 and / or CDK19 kinases, methods for modulating the β-catenin pathway, methods for modulating STAT1 activity, methods for modulating the TGFβ / BMP pathway, methods for modulating HIF-1 alpha activity in a cell, and methods for increasing BIM expression to induce apoptosis using a compound of formulas (A), (B), (C), (D) or (E). In addition, point mutants CDK8 and CDK19 and methods for their use are presented.