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Novel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors.

Authors :
Koltun DO
Parkhill EQ
Vasilevich NI
Glushkov AI
Zilbershtein TM
Ivanov AV
Cole AG
Henderson I
Zautke NA
Brunn SA
Mollova N
Leung K
Chisholm JW
Zablocki J
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Apr 01; Vol. 19 (7), pp. 2048-52. Date of Electronic Publication: 2009 Feb 08.
Publication Year :
2009

Abstract

We identified a series of structurally novel SCD (Delta9 desaturase) inhibitors via high-throughput screening and follow-up SAR studies. Modification of the central bicyclic scaffold has proven key to our potency optimization effort. The most potent analog (8g) had IC(50) value of 50 pM in a HEPG2 SCD assay and has been shown to be metabolically stable and selective against Delta5 and Delta6 desaturases.

Details

Language :
English
ISSN :
1464-3405
Volume :
19
Issue :
7
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
19249203
Full Text :
https://doi.org/10.1016/j.bmcl.2009.02.019