Discovery of novel bridged tetrahydronaphthalene derivatives as potent T/L-type calcium channel blockers

• Published in: Bioorganic & medicinal chemistry letters Vol. 25; no. 18; pp. 3941 - 3946
• Main Authors: Renneberg, Dorte, Hubler, Francis, Rey, Markus, Hess, Patrick, Delahaye, Stephane, Gatfield, John, Iglarz, Marc, Hilpert, Kurt
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.09.2015; Elsevier
• Subjects: Animals; Antihypertensive effect; Bridged tetrahydronaphthalene; Calcium channel blocker; Calcium Channel Blockers - chemical synthesis; Calcium Channel Blockers - chemistry; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; Drug Discovery; Life Sciences & Biomedicine; Mibefradil; Molecular Conformation; Pharmacology & Pharmacy; Physical Sciences; Rats; Rats, Inbred SHR; Science & Technology; Structure-Activity Relationship; T/L-type calcium channels; Tetrahydronaphthalenes - chemical synthesis; Tetrahydronaphthalenes - chemistry; Tetrahydronaphthalenes - pharmacology; OZBPEBNJOSXIBE-SKYBXZRDSA-N; Mibefradil; T/L-type calcium channels; Calcium channel blocker; Bridged tetrahydronaphthalene; Antihypertensive effect; CA2+ CHANNELS; INHIBITOR
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.07.038

[Display omitted] Chemical evolution of mibefradil resulted in the identification of novel bridged tetrahydronaphthalene derivatives as potent T/L-type calcium channel blockers. A SAR study, in vitro and in vivo DMPK properties as well as the in vivo antihypertensive effect in rats are presented.