Synthesis and biological activity of 4-(diphenylmethyl)-alpha-[(4-quinolinyloxy)methyl]-1-piperazineethanol and related compounds.
A series of 4-(diphenylmethyl)-alpha-[(4-quinolinyloxy)methyl]-1-pipe razineethanol and closely related compounds was synthesized and evaluated for cardiac and vascular activity in isolated perfused rat and guinea pig hearts. Compound 1 produced greater inotropic effects in rat hearts than in guinea pig hearts, a phenomenon which was also observed with the prototype agent DPI 201-106. Compound 15 produced an inotropic effect with one-tenth the potency of compound 1. Both compounds 1 and 15 demonstrated direct inotropic and vasodilatory effects when administered iv in anesthetized dogs, although the vasodilatory activity was more pronounced with compound 15 than 1 and DPI compound. Compound 1 lacks the CN moiety which is a key structural requirement in DPI for positive inotropic activity. The synthesis, in vitro, and in vivo evaluations of these agents, and comparative data with DPI-201-106 (compound 17) are reported.
Sircar
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Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Haleen
S J
SJ
Burke
S E
SE
Barth
H
H
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D010879:Piperazines; D011804:Quinolines; C078278:4-(diphenylmethyl)-alpha-((quinolinyloxy)methyl)-1-piperazinoethanol; C046261:DPI 201-106