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1,7- and 2,7-naphthyridine derivatives as potent and highly specific PDE5 inhibitors.

Abstract：

:Novel 1,7- and 2,7-naphthyridine derivatives, designed by the introduction of nitrogen atom into the phenyl ring of previously reported 4-aryl-1-isoquinolinone derivatives, were disclosed as a new structural class of potent and specific PDE5 inhibitors. Among them, 2,7-naphthyridine 4c showed potent PDE5 inhibition (IC(50)=0.23 nM) and one of the best PDE5 specificities against PDEs1-4,6 (>100,000-fold selective versus PDE1-4, 240-fold selective vs PDE6). This compound showed more potent relaxant effects on isolated rabbit corpus cavernosum (EC(30)=5.0 nM) than Sildenafil (EC(30)=8.7 nM). The compound 4c (T-0156) was selected for further biological and pharmacological evaluation of erectile dysfunction.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Ukita T,Nakamura Y,Kubo A,Yamamoto Y,Moritani Y,Saruta K,Higashijima T,Kotera J,Fujishige K,Takagi M,Kikkawa K,Omori K

doi

10.1016/s0960-894x(03)00440-2

subject

Has Abstract

pub_date

2003-07-21 00:00:00

pages

2341-5

issue

14

eissn

0960-894X

issn

1464-3405

pii

S0960894X03004402

journal_volume

13

pub_type

杂志文章

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