53985-44-7Relevant articles and documents
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.
BIARYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PHARMACEUTICALS
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, (2014/10/15)
The present invention relates to compounds of the formula (I), wherein X, R, R1, R2, D, E1, E2, E3, E4, G1, G2, G3 and G4 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease ca
3-Aminopyrrolidinone farnesyltransferase inhibitors: Design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency
Bell, Ian M.,Gallicchio, Steven N.,Abrams, Marc,Beese, Lorena S.,Beshore, Douglas C.,Bhimnathwala, Hema,Bogusky, Michael J.,Buser, Carolyn A.,Culberson, J. Christopher,Davide, Joseph,Ellis-Hutchings, Michelle,Fernandes, Christine,Gibbs, Jackson B.,Graham, Samuel L.,Hamilton, Kelly A.,Hartman, George D.,Heimbrook, David C.,Homnick, Carl F.,Huber, Hans E.,Huff, Joel R.,Kassahun, Kelem,Koblan, Kenneth S.,Kohl, Nancy E.,Lobell, Robert B.,Lynch Jr., Joseph J.,Robinson, Ronald,Rodrigues, A. David,Taylor, Jeffrey S.,Walsh, Eileen S.,Williams, Theresa M.,Zartmant, C. Blair
, p. 2388 - 2409 (2007/10/03)
A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear 3-aminopyrrolidinone FTIs such as compound 1, macrocycles such as 49 combined improved pharmacokinetic prope
