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• W2023659437 abstract "We synthesized various 4-(3-chloro-4-methoxybenzyl)aminophthalazines substituted at the 1- and 6-positions and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) and their vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F2α (10-5 M). The preferred substituents at the 1-position of the phthalazine were 4-hydroxypiperidino, 4-hydroxymethylpiperidino, 4-(2-hydroxyethyl)piperidino, and 4-oxopiperidino. Among these compounds, [4-(3-chloro-4-methoxybenzyl)amino-1-(4-hydroxy)piperidino]-6-phthalazinecarbonitrile monohydrochloride (13) exhibited potent PDE5 inhibitory activity (IC50 = 0.56 nM) with >1700-fold high selectivity over other PDE isozymes (PDE1−4). Compound 13 exhibited the most potent vasorelaxant action (EC50 = 13 nM) in this series of compounds. Compound 13 reduced mean pulmonary arterial pressure by 29.9 ± 3.1% when administered intravenously at 30 μg/kg to the chronically hypoxic rats and had an apparent oral bioavailability of about 19.5% in rats and was selected for further biological evaluation." @default.
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• W2023659437 date "2000-06-01" @default.
• W2023659437 modified "2023-10-17" @default.
• W2023659437 title "4-(3-Chloro-4-methoxybenzyl)aminophthalazines: Synthesis and Inhibitory Activity toward Phosphodiesterase 5" @default.
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• W2023659437 doi "https://doi.org/10.1021/jm9905054" @default.
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