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Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity.

Abstract：

:Novel 3,4-diarylpyrazolines 1 as potent CB1 receptor antagonists with lipophilicity lower than that of SLV319 are described. The key change is the replacement of the arylsulfonyl group in the original series by a dialkylaminosulfonyl moiety. The absolute configuration (4S) of eutomer 24 was established by X-ray diffraction analysis and 24 showed a close molecular fit with rimonabant in a CB1 receptor-based model. Compound 17 exhibited the highest CB1 receptor affinity (Ki = 24 nM) in this series, as well as very potent CB1 antagonistic activity (pA2 = 8.8) and a high CB1/CB2 subtype selectivity (approximately 147-fold).

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Lange JH,van Stuivenberg HH,Veerman W,Wals HC,Stork B,Coolen HK,McCreary AC,Adolfs TJ,Kruse CG

doi

10.1016/j.bmcl.2005.07.054

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

4794-8

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(05)01013-9

journal_volume

15

pub_type

杂志文章

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