BENZOIMIDAZOLE DERIVATIVES AS SIRTUIN (SIR) MODULATING COMPOUNDS

摘要

A. Provided herein are novel sirtuin-modulating compounds of formula (I) and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent ( I ), wherein: one of R1 R2 R3 or R4 is selected from a 5- to 6-membered heteroaryl comprising 1 to 3 heteroatoms 'independently selected from N, O or S, wherein said heteroaryl is optionally benzofused or optionally fused to a second 5- to 6-membered heteroaryl comprising 1 to 3 heteroatoms independently selected from N, O or S and is bound to the rest of the compound via a carbon ring atom, wherein said heteroaryl is optionally substituted on a single carbon ring atom with a substituent selected from a solubilizing group, or a C1-C4 straight or branched alkyl.