title: Discovery of novel bridged tetrahydronaphthalene derivatives as potent T/L-type calcium channel blockers.
abstract: 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.
authors.affiliation: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland. Electronic address: dorte.renneberg@actelion.com.
authors.forename: Dorte
authors.initials: D
authors.lastname: Renneberg
authors.affiliation: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: Francis
authors.initials: F
authors.lastname: Hubler
authors.affiliation: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Rey
authors.affiliation: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hess
authors.affiliation: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: Stephane
authors.initials: S
authors.lastname: Delahaye
authors.affiliation: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: John
authors.initials: J
authors.lastname: Gatfield
authors.affiliation: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Iglarz
authors.affiliation: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: Kurt
authors.initials: K
authors.lastname: Hilpert
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D008968:Molecular Conformation; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013764:Tetrahydronaphthalenes
keywords: Antihypertensive effect; Bridged tetrahydronaphthalene; Calcium channel blocker; Mibefradil; T/L-type calcium channels