Synthesis and modifications of a small library of 1,4-benzodiazepin-3-ones toward potential inhibitors of the collagen-von Willebrand Factor interaction

Deschrijver, Tiny; Verwilst, Peter; Broos, Katleen; Deckmyn, Hans; Dehaen, Wim; De Borggraeve, Wim

doi:10.1016/j.tet.2009.03.095

Synthesis and modifications of a small library of 1,4-benzodiazepin-3-ones toward potential inhibitors of the collagen-von Willebrand Factor interaction

Author:

Deschrijver, Tiny

Verwilst, Peter ; Broos, Katleen ; Deckmyn, Hans ; Dehaen, Wim ; De Borggraeve, Wim

Keywords:

angiotensin-ii, receptor antagonists, factor a3-domain, beta-hairpins, antibody, benzodiazepine, conformation, binding, design, platelets, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, BETA-TURNS, CONFORMATION, ANTIBODY, BINDING, DESIGN, PLATELETS, ADHESION, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, Organic Chemistry, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

A library of 1,4-benzodiazepin-3-one-based turn mimetics were synthesized and tested for their antithrombotic abilities. These mimetics are designed to incorporate amino acid side chains of the previously reported paratope of the inhibitory anti-von Willebrand Factor antibody 82D6A3. Modifications were performed oil the scaffolds by alkylation of the N-1-position and acylation of the reduced nitro group. Hereby the number of functional groups incorporated oil the core was expanded. (C) 2009 Elsevier Ltd. All rights reserved.