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作为潜在抗抑郁药的非钙依赖性磷酸二酯酶抑制剂：[3 -（双环烷氧基）- 4 - 甲氧基苯基]-2-咪唑烷酮

Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones.

作者信息

Saccomano N A, Vinick F J, Koe B K, Nielsen J A, Whalen W M, Meltz M, Phillips D, Thadieo P F, Jung S, Chapin D S

机构信息

Central Research, Pfizer Inc., Groton, Connecticut 06340.

出版信息

J Med Chem. 1991 Jan;34(1):291-8. doi: 10.1021/jm00105a045.

DOI:10.1021/jm00105a045
PMID:1992129
Abstract

The synthesis and biological properties of a novel series of selective calcium-independent phosphodiesterase inhibitors are described. These compounds also inhibit the specific binding of [3H]rolipram to rat brain membranes and exhibit efficacy in preclinical models of antidepressant activity in mice, such as reducing immobility in the forced-swim test and reversing reserpine-induced hypothermia. Imidazolidinones 4 and 16 were found to be the most potent compounds studied.

摘要

描述了一系列新型选择性非钙依赖性磷酸二酯酶抑制剂的合成及其生物学特性。这些化合物还抑制[³H]罗匹尼罗与大鼠脑膜的特异性结合，并在小鼠抗抑郁活性的临床前模型中显示出疗效，例如在强迫游泳试验中减少不动时间，并逆转利血平诱导的体温过低。发现咪唑烷酮4和16是所研究的最有效的化合物。

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