Discovery and SAR of 4-aminopyrrolidine-2-carboxylic acid correctors of CFTR for the treatment of cystic fibrosis

Autor:	Marc J C, Scanio, Xenia B, Searle, Bo, Liu, John R, Koenig, Robert J, Altenbach, Gregory A, Gfesser, Andrew, Bogdan, Stephen, Greszler, Gang, Zhao, Ashvani, Singh, Yihong, Fan, Andrew M, Swensen, Timothy, Vortherms, Arlene, Manelli, Corina, Balut, Wenqing, Gao, Hong, Yong, Michael, Schrimpf, Chris, Tse, Philip, Kym, Xueqing, Wang
Rok vydání:	2022
Předmět:	Cystic Fibrosis Proline Organic Chemistry Clinical Biochemistry Cystic Fibrosis Transmembrane Conductance Regulator Pharmaceutical Science Biochemistry Structure-Activity Relationship Mutation Drug Discovery Humans Molecular Medicine Benzodioxoles Molecular Biology
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 72:128843
ISSN:	0960-894X
Popis:	Cystic fibrosis (CF) is an autosomal recessive disease resulting from mutations on both copies of the CFTR gene. Phenylalanine deletion at position 508 of the CFTR protein (F508del-CFTR) is the most frequent mutation in CF patients. Currently, the most effective treatments of CF use a dual or triple combination of CFTR correctors and potentiators. In triple therapy, two correctors (C1 and C2) and a potentiator are employed. Herein, we describe the identification and exploration of the SAR of a series of 4-aminopyrrolidine-2-carboxylic acid C2 correctors of CFTR to be used in conjunction with our existing C1 corrector series for the treatment of CF.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::15a2a884faa7901f5e486831d30b03cd https://doi.org/10.1016/j.bmcl.2022.128843 Zobrazit plný text záznamu Full Text from ScienceDirect