Amide-functionalized 1,2,4-Triazol-5-amines as Covalent Inhibitors of Blood Coagulation Factor XIIa and Thrombin.


Journal

ACS pharmacology & translational science
ISSN: 2575-9108
Titre abrégé: ACS Pharmacol Transl Sci
Pays: United States
ID NLM: 101721411

Informations de publication

Date de publication:
09 Dec 2022
Historique:
received: 21 10 2022
entrez: 16 12 2022
pubmed: 17 12 2022
medline: 17 12 2022
Statut: epublish

Résumé

To counteract thrombosis, new safe and efficient antithrombotics are required. We herein report the design, synthesis, and biological activity of a series of amide-functionalized acylated 1,2,4-triazol-5-amines as selective inhibitors of blood coagulation factor XIIa and thrombin. The introduction of an amide moiety into the main scaffold of 3-aryl aminotriazoles added certain three-dimensional properties to synthesized compounds and allowed them to reach binding sites in FXIIa and thrombin previously unaddressed by non-functionalized 1,2,4-triazol-5-amines. Among synthesized compounds, one quinoxaline-derived aminotriazole bearing

Identifiants

pubmed: 36524012
doi: 10.1021/acsptsci.2c00204
pmc: PMC9745896
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1318-1347

Informations de copyright

© 2022 The Authors. Published by American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Lukas Imberg (L)

Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster 48149, Germany.

Simon Platte (S)

Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster 48149, Germany.

Catharina Erbacher (C)

Institute of Inorganic and Analytical Chemistry, University of Münster, Münster 48149, Germany.

Constantin G Daniliuc (CG)

Institute for Organic Chemistry, University of Münster, Münster 48149, Germany.

Svetlana A Kalinina (SA)

Institute of Food Chemistry, University of Münster, Münster 48149, Germany.

Wolfgang Dörner (W)

Institute of Biochemistry, University of Münster, Münster 48149, Germany.

Antti Poso (A)

School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio 70211, Finland.
Department of Internal Medicine VIII, University Hospital Tübingen, Tübingen 72076, Germany.

Uwe Karst (U)

Institute of Inorganic and Analytical Chemistry, University of Münster, Münster 48149, Germany.

Dmitrii V Kalinin (DV)

Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster 48149, Germany.

Classifications MeSH