Inotropic polyazapentalene sulmazole analogues.
Aryl substituted 1H-imidazo[1,2-a]imidazole 8, imidazo[2,1-b]thiazole 9, 1,4-dihydroimidazo[4,5-d]imidazole 11, and 1(2),4-dihydroimidazo[4,5-c]pyrazoles 12-17 have been prepared. An X-ray crystallographic study confirmed the structure of 8 and showed this analogue to exist as the 1H-tautomer. These heterocycles were evaluated as inotropic agents and analogues 12, 15, and 17 found to display inotropic properties which were less potent in vitro, but more potent in vivo, than those of sulmazole. Structure-activity relationships are discussed.
Barraclough
P
P
Department of Medicinal Chemistry, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Black
J W
JW
Cambridge
D
D
Firmin
D
D
Gerskowitch
V P
VP
Glen
R C
RC
Giles
H
H
Gillam
J M
JM
Hull
R A
RA
Iyer
R
R
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D006168:Guinea Pigs; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D007093:Imidazoles; C029758:sulmazole