Discovery of Novel 2-Carbamoyl Morpholine Derivatives as Highly Potent and Orally Active Direct Renin Inhibitors.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
11 Aug 2022
11 Aug 2022
Historique:
received:
16
06
2022
accepted:
26
07
2022
entrez:
18
8
2022
pubmed:
19
8
2022
medline:
19
8
2022
Statut:
epublish
Résumé
The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure. Renin, the first and rate-limiting enzyme of the RAAS, is an attractive target for the treatment of hypertension and cardiovascular/renal diseases. Therefore, various direct renin inhibitors (DRIs) have been researched over recent decades; however, most exhibited poor pharmacokinetics and oral bioavailability due to the peptidomimetic or nonpeptidomimetic structures with a molecular weight (MW) of >600, and only aliskiren is approved. This study introduces a novel class of DRIs comprised of a 2-carbamoyl morpholine scaffold. These compounds have a nonpeptidomimetic structure and a MW of <500. The representative compound
Identifiants
pubmed: 35978678
doi: 10.1021/acsmedchemlett.2c00280
pmc: PMC9377009
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1351-1357Informations de copyright
© 2022 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare the following competing financial interest(s): D.I., H.S., N.A., Y.T., Y.T., T.T., H.A., T.K., K.T., A.K., M.N., Y.I., H.Y. and T.I. were employed by Mitsubishi Tanabe Pharma Corporation at the time this work was done; J.X., J.S., Y.K. and G.X. were employed by Shanghai Pharmaceuticals Holding Co., Ltd. at the time this work was done.
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