Cyclic GMP phosphodiesterase inhibitors. 2. Requirement of 6-substitution of quinazoline derivatives for potent and selective inhibitory activity

Y Takase, T Saeki, N Watanabe, H Adachi…

Index: Takase, Yasutaka; Saeki, Takao; Watanabe, Nobuhisa; Adachi, Hideyuki; Souda, Shigeru; Saito, Isao Journal of Medicinal Chemistry, 1994 , vol. 37, # 13 p. 2106 - 2111

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Citation Number: 63

Abstract

We synthesized various 4-[[3, 4-(methylenedioxy) benzylyllaminolquinazolines substituted at the 5-to 8-positions and evaluated their inhibitory activities toward cyclic GMP phosphodiesterase (cGMP-PDE) from porcine aorta. Monosubstitution at the &position wae essential for the inhibitory activity, and the preferred Substituents were compact and hydrophobic: methoxy (3b, ICs0= 0.23 pM), methyl (3c, 0.10 pM), chloro (3d, 0.019 pM), ...