title: Benzazepinone calcium channel blockers. 3. Synthesis and structure-activity studies of 3-alkylbenzazepinones.
abstract: As part of a program aimed at identifying novel analogues of diltiazem, we developed several synthetic routes for 3-alkylbenzazepinones, both in racemic and nonracemic form. Structure-activity relationship studies in this series have led to identification of several analogues as potent calcium channel blocking agents, both in vitro and in vivo. Analogues containing a 6-trifluoromethyl substituent (17a and 17b) are the most potent vasorelaxants in vitro. The oral antihypertensive activity of these compounds is comparable to its 3-acetoxy derivative 1 (X = 6-CF3) and 8-chlorodiltiazem (2b). The 3-allyl analogue 17c is a more potent antihypertensive agent than 17a, 17b, or 8-chlorodiltiazem (2b), and has a longer duration of action in vivo.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
authors.forename: J
authors.initials: J
authors.lastname: Das
authors.forename: D M
authors.initials: DM
authors.lastname: Floyd
authors.forename: S D
authors.initials: SD
authors.lastname: Kimball
authors.forename: K J
authors.initials: KJ
authors.lastname: Duff
authors.forename: T C
authors.initials: TC
authors.lastname: Vu
authors.forename: M W
authors.initials: MW
authors.lastname: Lago
authors.forename: R V
authors.initials: RV
authors.lastname: Moquin
authors.forename: V G
authors.initials: VG
authors.lastname: Lee
authors.forename: J Z
authors.initials: JZ
authors.lastname: Gougoutas
authors.forename: M F
authors.initials: MF
authors.lastname: Malley
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006168:Guinea Pigs; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008968:Molecular Conformation; D015394:Molecular Structure; D009132:Muscles / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects; D014961:X-Ray Diffraction
chemical_list: D000959:Antihypertensive Agents; D001552:Benzazepines; D002121:Calcium Channel Blockers