Novel selective PDE4 inhibitors. 2. Synthesis and structure-activity relationships of 4-aryl-substituted cis-tetra-and cis-hexahydrophthalazinones

…, IJ Van der Laan, GJ Sterk, U Thibaut…

Index: Van der Mey; Hatzelmann; Van Klink; Van der Laan; Sterk; Thibaut; Ulrich; Timmerman Journal of Medicinal Chemistry, 2001 , vol. 44, # 16 p. 2523 - 2535

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Citation Number: 46

Abstract

A series of 4-aryl-substituted cis-4a, 5, 8, 8a-tetra-and cis-4a, 5, 6, 7, 8, 8a-hexahydro-2 H- phthalazin-1-ones with high inhibitory activity toward cAMP-specific phosphodiesterase (PDE4) was synthesized. To study structure-activity relationships various substituents were introduced to the 2-, 3-, and 4-positions of the 4-phenyl ring. Substitution at the 4-position of the phenyl ring was restricted to a methoxy group, probably due to unfavorable steric ...