Calpain modulators and therapeutic uses thereof

Abstract

Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.

Description

technical field [0001] The present invention relates to the fields of chemistry and medicine. More specifically, the present invention relates to non-macrocyclic alpha-ketoamide compounds, compositions, methods for their preparation and their use as therapeutic agents as small molecule calpain modulators. Background technique [0002] Fibrotic diseases account for an estimated 45% of deaths in developed countries, yet the development of treatments for these diseases is still in its infancy. Current treatments for fibrotic diseases, such as idiopathic pulmonary fibrosis, renal fibrosis, systemic sclerosis, and cirrhosis, are few in number and only alleviate some of the symptoms of fibrosis without treating the underlying cause. [0003] Despite the current limited understanding of the different etiologies that cause these conditions, the phenotypic similarities of affected organs in fibrotic diseases strongly support the existence of common pathogenic pathways. A major driv...

AI Technical Summary

Problems solved by technology

Unfortunately, TGFβ is a pleiotropic cytokine with many physiological functions, such that global inhibition of TGFβ signaling is also associated with severe side effects

Additionally, current data suggest that this proximal inhibition may be susceptible to pathological resolution strategies (i.e., due to redundancy or compensation), which would limit the utility of these drugs

Further complicating the issue is that in cancer, TGFβ signaling acts early on as an anti-tumor growth suppressor but then becomes a tumor-promoting agent and is so strongly required to selectively inhibit another virulence factor of signaling reason

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