121375-11-9

Upstream product

• 108857-35-8 1-(4-amino-3-formyl-5-methylphenyl)-2,4-dimethylimidazole 
• 459-73-4 GlyOEt*HCl 
• 108857-38-1 1-(4-amino-3-cyano-5-methylphenyl)-2,4-dimethylimidazole 
• 108857-39-2 1-(4-Amino-3-bromo-5-methylphenyl)-2,4-dimethylimidazole 
• 102792-03-0 1-(4-Amino-3-methylphenyl)-2,4-dimethylimidazole 
• 121375-16-4 {[1-[2-Amino-5-(2,4-dimethyl-imidazol-1-yl)-3-methyl-phenyl]-meth-(E)-ylidene]-amino}-acetic acid ethyl ester 

Downstream Products

• 108892-68-8 7-(2,4-dimethylimidazol-1-yl)-9-methyl-1,2,3,5-tetrahydroimidazo<2,1-b>quinazolin-2(1H)-one 
• 108857-20-1 ethyl N-cyano-N-<<2-amino-3-methyl-5-(2,4-dimethylimidazol-1-yl)phenyl>methyl>glycinate 

Relevant academic research and scientific papers

7-Heteroaryl-1,2,3,5-tetrahydroimidazoquinazolin-2(1H)-one Derivatives with Cardiac Stimulant Activity

A series of 7-heteroaryl-1,2,3,5-tetrahydroimidazoquinazolin-2(1H)-ones was synthesized and evaluated in dogs for cardiac stimulant activity.Compounds were obtained by a palladium-catalyzed cross-coupling reaction between a heteroarylzinc chloride and a 7-iodo-1,2,3,5-tetrahydroimidazoquinazolin-2(1H)-one or by cyclization of an N-glycinate with cyanogen bromide.Compared to the parent ring system (3), introduction of a 2,6-dimethylpyridin-3-yl (6), 2,4-dimethylimidazol-1-yl (7), or 1,2,4-triazol-1-yl (8) moiety at the 7-position led to a 13-17-fold increase in positive inotropic activity (percentage increase in dP(dtmax) in anesthetized dogs.Potency could be further enhanced with a 9-methyl substituent (10-12).The most potent member of the series, 7-(2,4-dimethylimidazol-1-yl)-9-methyl-1,2,3,5-tetrahydroimidazoquinazolin-2(1H)-one (11) (23percent increase in dP/dtmax, 2 μg/kg), was 80 times more active than 3 and displayed a 5-fold advantage over milrinone.In conscious dogs, 6 elicited marked and sustained positive inotropic activity (decrease in QA interval) after oral administration (1 mg/kg), whereas 10-12 were 10 times more potent. 11 produced an obvious increase in cardiac contractility (20percent increase in dP/dtmax) at low dose levels (25 μg/kg) while, after 100 μ/kg, the marked response (50percent increase in dP/dtmax) was maintained for the whole 7-h test period.In these experiments, 11 had no effect on heart rate, and the compound also displayed exceptional selectivity for increasing the force rather than the rate of cardiac contraction (> 150percent increase in dP/dtmax) in the Starling heart-lung preparation.These studies demonstrate that the tetrahydroimidazoquinazolinone nucleus is an effective bioisostere for the 2(1H)-quinolinone system and that 11 displays improved cardiac stimulant activity and duration of action when compared to milrinone.

Tetrahydroimidazoquinazolinone inotropic agents

A series of novel heterocyclic-substituted 1,2,3,5-tetrahydroimidazo(2,1-b)quinazolin-2-(1H)-one compounds have been prepared, including their pharmaceutically acceptable salts, wherein the heterocyclic ring moiety is an optionally substituted 5- or 6-membered aromatic heterocyclic group attached to the 6-, 7-, 8- or 9-positions of the aforesaid tetrahydroquinaxolinone ring. These particular compounds are useful in therapy as highly potent inotropic and therefore, are of value in the treatment of various cardiac conditions. Preferred member compounds include 7-(2,4-dimethylimidaxol-1-yl)-9-methyl-1,2,4,5,-tetrahydroimidazo (2,1-b)quinazolin-2-(1H)-one, 3,9-dimethyl-7-(2,4-dimethylimidazol-1-yl) -1,2,3,5-tetrahydroimidazo(2,1-b)quinazolin-2-(1H)-one and 9-methyl-7 -(1,2,4-triazol-4-yl)-1,2,3,5-tetrahydroimidazo(2,1-b)quinazolin-2-(1H)-one, respectively. Methods for preparing these compounds from known starting materials are provided.