Discovery and evaluation of Ca v 3.1-selective T-type calcium channel blockers.

Autor: Bezençon O; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland. Electronic address: olivier.bezencon@idorsia.com., Remeň L; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland., Richard S; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland., Roch C; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland., Kessler M; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland., Moon R; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland., Mawet J; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland., Ertel EA; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland., Pfeifer T; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland., Capeleto B; Drug Discovery Chemistry, Biology and Pharmacology, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Dec 01; Vol. 27 (23), pp. 5322-5325. Date of Electronic Publication: 2017 Oct 03.
DOI: 10.1016/j.bmcl.2017.09.063
Abstrakt: We identified and characterized a series of pyrazole amides as potent, selective Ca v 3.1-blockers. This series culminated with the identification of pyrazole amides 5a and 12d, with excellent potencies and/or selectivities toward the Ca v 3.2- and Ca v 3.3-channels. This compound displays poor DMPK properties, making its use difficult for in vivo applications. Nevertheless, this compound as well as analogous ones are well-suited for in vitro studies.
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Databáze: MEDLINE
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