Inotropic "A" ring substituted sulmazole and isomazole analogues.
A series of "A" ring substituted sulmazole and isomazole analogues have been prepared and evaluated as inotropic agents. pKA's, protonation sites, and log P values were measured for selected compounds and their electronic properties were calculated. No simple correlation between inotropic activity and pKA, protonation site, or log P value was observed. However, in vitro inotropism did correlate with the calculated charge density of the "B" ring imidazo nitrogen atom. The 6-position of sulmazole appeared to be the most tolerant toward substituents, the 6-amino derivative 7 being a more potent inotrope than sulmazole itself. 4-Methoxyisomazole 13 had comparable in vivo inotropic properties to those of isomazole.
Barraclough
P
P
Department of Medicinal Chemistry, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Black
J W
JW
Cambridge
D
D
Collard
D
D
Firmin
D
D
Gerskowitch
V P
VP
Glen
R C
RC
Giles
H
H
Hill
A P
AP
Hull
R A
RA
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004563:Electrochemistry; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D015394:Molecular Structure; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011522:Protons; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D007093:Imidazoles; D011522:Protons; C065061:6-aminosulmazole; C065062:4-methoxyisomazole; C029758:sulmazole