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Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2.

Abstract：

:PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Nankervis JL,Feil SC,Hancock NC,Zheng Z,Ng HL,Morton CJ,Holien JK,Ho PW,Frazzetto MM,Jennings IG,Manallack DT,Martin TJ,Thompson PE,Parker MW

doi

10.1016/j.bmcl.2011.09.109

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

7089-93

issue

23

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01353-9

journal_volume

21

pub_type

杂志文章

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