Cyclic guanidines. 17. Novel (N-substituted amino)imidazo[2,1-b]quinazolin-2-ones: water-soluble platelet aggregation inhibitors

Abstract

A series of novel 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one derivatives substituted with a secondary amino group has been prepared and tested for the activities of inhibiting platelet aggregation in rats in vitro and ex vivo. Most of the compounds were found to be the potent inhibitors of platelet aggregation. Some of the active compounds were soluble in water and effective via iv infusion in rats. Structure-activity relationships have indicated that a lipophilic secondary amino group located at position 6 or 7 contributed to retention of potent activity. Among the compounds studied, 7-piperidino-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2- one (13 g,DN-9693) was the most favorable compound.

Preparation of Water-Soluble Compounds by Covalent Attachment of Solubilizing Moieties

“…The hydrochloride salt of the camptothecin derivative (a) (Figure 30.16) is soluble in water at concentrations up to 1 mg/mL. Similar results were obtained in solubilizing the benzodiazepine (b) [75] and the quinazolinone (c) [76]. Similar results were obtained in solubilizing the benzodiazepine (b) [75] and the quinazolinone (c) [76].…”

Effects of DN-9693, a Selective Inhibitor of Cyclic AMP Phosphodiesterase, in Isolated and Perfused Canine Large Coronary Arteries

“…In 1985, DN-9693 was developed as one of the water-soluble platelet aggregation inhibitors (1). Moreover, DN-9693 has been demon strated to inhibit selectively cyclic AMP PDE (isozyme III) in platelets (2).…”

Preparation of Water-Soluble Compounds by Covalent Attachment of Solubilizing Moieties

“…The hydrochloride salt of the camptothecin derivative (a) ( Figure 38.15 ) is soluble in water at concentrations up to 1 mg/mL; the comparable value for camptothecin itself is 0.0025 mg/mL. 69 The adenosine A 1 antagonist KW-3902 (d) was solubilized in an original manner by converting it to an amidinic and cyclized bioisostere (e 69 The adenosine A 1 antagonist KW-3902 (d) was solubilized in an original manner by converting it to an amidinic and cyclized bioisostere (e …”