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Discovery of novel 7-membered cyclic amide derivatives that inhibit 11beta-hydroxysteroid dehydrogenase type 1.

Abstract：

:A series of novel 5-trans-hydroxyadamantan-2-yl-5,6,7,8-tetrahydropyrazolo[4,3-c]azepin-4(1H)-ones that inhibit 11beta-hydroxysteroid dehydrogenase type 1 are described. We discovered these 7-membered cyclic amide derivatives by introducing a distinctive linker through pharmacophore analysis of known ligands included in X-ray co-crystal structures. Further optimization using docking studies led to highly potent inhibitors 15b and 27, which furthermore showed the potent efficacy in in vivo studies.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Udagawa S,Sakami S,Takemura T,Sato M,Arai T,Nitta A,Aoki T,Kawai K,Iwamura T,Okazaki S,Takahashi T,Kaino M

doi

10.1016/j.bmcl.2013.01.090

subject

Has Abstract

pub_date

2013-03-15 00:00:00

pages

1617-21

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00123-6

journal_volume

23

pub_type

杂志文章

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