当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Nonsteroidal glucocorticoid agonists: tetrahydronaphthalenes with alternative steroidal A-ring mimetics possessing dissociated (transrepression/transactivation) efficacy selectivity.

Nonsteroidal glucocorticoid agonists: tetrahydronaphthalenes with alternative steroidal A-ring mimetics possessing dissociated (transrepression/transactivation) efficacy selectivity.

Abstract：

:The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NFkappaB glucocorticoid receptor (GR) agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). Quinolones, indoles, and C- and N-linked quinolines are some of the heterocycles that provide efficacy selectivity. For example, the isoquinoline 49D1E2 has NFkappaB agonism with pIC50 of 8.66 (89%) and reduced efficacy in MMTV agonism (6%), and the quinoline 55D1E1 has NFkappaB agonism with pIC50 of 9.30 (101%) and reduced efficacy in MMTV agonism with pEC50 of 8.02 (47%). A description of how a compound from each class is modeled in the active site of the receptor is given.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Biggadike K,Boudjelal M,Clackers M,Coe DM,Demaine DA,Hardy GW,Humphreys D,Inglis GG,Johnston MJ,Jones HT,House D,Loiseau R,Needham D,Skone PA,Uings I,Veitch G,Weingarten GG,McLay IM,Macdonald SJ

doi

10.1021/jm070778w

subject

Has Abstract

pub_date

2007-12-27 00:00:00

pages

6519-34

issue

26

eissn

0022-2623

issn

1520-4804

journal_volume

50

pub_type

杂志文章

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