Parallel solid-phase synthesis of zatebradine analogues as potential I(f) channel blockers.
The first solid-phase synthesis of zatebradine 1 and its analogues is reported. This has resulted in the preparation of compounds with increased ability to reduce the spontaneous beating of isolated guinea-pig atria in a concentration-dependent manner. One example, 8g, showed a maximum reduction of beating of 80% at 3 microM compared to a reduction of 40% at 3 microM with zatebradine 1.
Bom
A
A
Pharmacology Department, Organon Laboratories Ltd, Newhouse, Lanarkshire, ML1 5SH, Scotland, UK.
Booth
S
S
Bruin
J
J
Clark
J
J
Miller
S
S
Wathey
B
B
D000818:Animals; D016275:Atrial Function; D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000737:chemistry* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D013329:Structure-Activity Relationship
C442389:3-((allyl)(2-(4-methoxyphenyl)ethyl)amino)propyl-7,8-dimethoxy-1H-benzazepin-2-one; D001552:Benzazepines; D002316:Cardiotonic Agents; C043636:zatebradine