| Literature DB >> 16140010 |
Jos H M Lange1, Herman H van Stuivenberg, Willem Veerman, Henri C Wals, Bob Stork, Hein K A C Coolen, Andrew C McCreary, Tiny J P Adolfs, Chris G Kruse.
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).Entities:
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Year: 2005 PMID： 16140010 DOI： 10.1016/j.bmcl.2005.07.054
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823