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8-Substituted analogues of 3-(3-cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine: highly potent and selective PDE4 inhibitors.

Abstract：

:3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine V11294 (1) has been identified as a lead structure, which selectively inhibits human lung PDE4 (436 nM) and is also active in a number of in vitro and in vivo models of inflammation. Here we describe the synthesis and pharmacology of a series of highly potent 8-[(benzyloxy)methyl]-substituted analogues, with potencies in the range 10-300 nM. In addition, several compounds showed interesting PDE4 subtype specificities, for example, the 3-thienyl derivative 5v, which showed 6-10 nM potency at PDE4B, D3, and D5 and a 20- to 200-fold selectivity over A and D2, respectively.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Whitehead JW,Lee GP,Gharagozloo P,Hofer P,Gehrig A,Wintergerst P,Smyth D,McCoull W,Hachicha M,Patel A,Kyle DJ

doi

10.1021/jm030603w

keywords:

subject

Has Abstract

pub_date

2005-02-24 00:00:00

pages

1237-43

issue

4

eissn

0022-2623

issn

1520-4804

journal_volume

48

pub_type

杂志文章

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