Discovery and SAR of 4-aminopyrrolidine-2-carboxylic acid correctors of CFTR for the treatment of cystic fibrosis.
Cystic Fibrosis (CF)
Cystic Fibrosis Transmembrane Conductance Regulator Protein (CFTR)
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 09 2022
15 09 2022
Historique:
received:
04
04
2022
revised:
31
05
2022
accepted:
02
06
2022
pubmed:
11
6
2022
medline:
27
7
2022
entrez:
10
6
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35688367
pii: S0960-894X(22)00319-5
doi: 10.1016/j.bmcl.2022.128843
pii:
doi:
Substances chimiques
Benzodioxoles
0
CFTR protein, human
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
4-aminopyrrolidine-2-carboxylic acid
99146-69-7
Proline
9DLQ4CIU6V
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
128843Informations de copyright
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