作为治疗勃起功能障碍的强效和选择性磷酸二酯酶5（PDE5）抑制剂的呋喃甲酰基和苯并呋喃甲酰基吡咯并喹诺酮类化合物

Furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors for treatment of erectile dysfunction.

作者信息

Jiang Weiqin, Sui Zhihua, Macielag Mark J, Walsh Shawn P, Fiordeliso James J, Lanter James C, Guan Jihua, Qiu Yuhong, Kraft Patricia, Bhattacharjee Sheela, Craig Elizabeth, Haynes-Johnson Donna, John T Matthew, Clancy Joanna

机构信息

Johnson & Johnson Pharmaceutical Research & Development L.L.C., 1000 Route 202 South, P.O. Box 300, Raritan, New Jersey 08869, USA.

出版信息

J Med Chem. 2003 Jan 30;46(3):441-4. doi: 10.1021/jm0202573.

DOI:10.1021/jm0202573

PMID:12540243

Abstract

Synthesis of furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors was reported. Their in vitro potencies in inhibiting PDE5 and selectivity in inhibiting other PDE isozymes (PDE1-4 and PDE6) were evaluated. Some of these compounds are more potent than sildenafil with better selectivity toward PDE1 and PDE6. Incorporation of solublizing groups resulted in bioavailable analogues. Selected compounds showed in vivo efficacy in anesthetized dog model for penile erection.

摘要

据报道，合成了作为强效和选择性磷酸二酯酶5（PDE5）抑制剂的呋喃甲酰基和苯并呋喃甲酰基吡咯并喹诺酮类化合物。评估了它们在体外抑制PDE5的效力以及对其他磷酸二酯酶同工酶（PDE1 - 4和PDE6）的抑制选择性。其中一些化合物比西地那非更有效，且对PDE1和PDE6具有更好的选择性。引入增溶基团得到了具有生物利用度的类似物。所选化合物在麻醉犬阴茎勃起模型中显示出体内疗效。