616197-92-3Relevant academic research and scientific papers
BCL-2 INHIBITORS AND THEIR USE AS PHARMACEUTICALS
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Paragraph 0490-0491, (2021/11/13)
The disclosure is directed to, in part, to BCL-2 inhibitors, pharmaceutical compositions comprising the same, as well as methods of their use and preparation.
N-Phenylbenzamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore
Roy, Sudeshna,?ileikyte, Justina,Neuenswander, Benjamin,Hedrick, Michael P.,Chung, Thomas D. Y.,Aubé, Jeffrey,Schoenen, Frank J.,Forte, Michael A.,Bernardi, Paolo
, p. 283 - 288 (2016/02/16)
Persistent opening of the mitochondrial permeability transition pore (PTP), an inner membrane channel, leads to mitochondrial dysfunction and renders the PTP a therapeutic target for a host of life-threatening diseases. Herein, we report our effort toward identifying small-molecule inhibitors of this target through structure-activity relationship optimization studies, which led to the identification of several potent analogues around the N-phenylbenzamide compound series identified by high-throughput screening. In particular, compound 4 (3-(benzyloxy)-5-chloro-N-(4-(piperidin-1-ylmethyl)phenyl)benzamide) displayed noteworthy inhibitory activity in the mitochondrial swelling assay (EC50=280 nm), poor-to-very-good physicochemical as well as in vitro pharmacokinetic properties, and conferred very high calcium retention capacity to mitochondria. From the data, we believe compound 4 in this series represents a promising lead for the development of PTP inhibitors of pharmacological relevance.
