喹唑啉类作为强效且高度选择性的磷酸二酯酶5抑制剂，可作为男性勃起功能障碍的潜在治疗药物。

Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction.

作者信息

Kim Young Hoon, Choi Hojin, Lee Jaekwang, Hwang In-Chang, Moon Seung Kee, Kim Soo Jin, Lee Hong Woo, Im Dai Sig, Lee Sung Sook, Ahn Soon Kil, Kim Sang Woong, Han Cheol Kyu, Yoon Jeong Hyeok, Lee Kyung Joo, Choi Nam Song

机构信息

Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., PO Box 74, Chonan, Republic of Korea.

出版信息

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6279-82. doi: 10.1016/j.bmcl.2008.09.108. Epub 2008 Oct 11.

DOI:10.1016/j.bmcl.2008.09.108

PMID:18976905

Abstract

In an effort to minimize side effects associated with low selectivity against PDE isozymes, we have successfully identified a series of 6,7,8-substituted quinzaolines as potent inhibitors of PDE5 with high level of isozyme selectivity, especially against PDE6 and PDE11. PDE5 potency and isozyme selectivity of quinazolines were greatly improved with substitutions both at 6- and 8-position. The synthesis, structure-activity relationships and in vivo efficacy of this novel series of potent PDE5 inhibitors are described.

摘要

为了尽量减少因对磷酸二酯酶（PDE）同工酶选择性低而产生的副作用，我们已成功鉴定出一系列6,7,8-取代喹唑啉，它们是强效的PDE5抑制剂，具有高水平的同工酶选择性，尤其是对PDE6和PDE11。喹唑啉在6位和8位的取代极大地提高了其PDE5活性和同工酶选择性。本文描述了这一系列新型强效PDE5抑制剂的合成、构效关系及体内疗效。