Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem Lett. 2014 Mar 1;24(5):1437-41. doi: 10.1016/j.bmcl.2013.12.075. Epub 2013 Dec 27.

4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable stearoyl-CoA desaturase-1 (SCD1) inhibitors: part 2. Pyridazine-based analogs.

Author information

  • 1Cardiovascular and Metabolism Research, Janssen Research and Development, LLC, Welsh & McKean Roads, Spring House, PA 19477, USA. Electronic address: shyhyang99@yahoo.com.
  • 2Cardiovascular and Metabolism Research, Janssen Research and Development, LLC, Welsh & McKean Roads, Spring House, PA 19477, USA.

Abstract

Design, synthesis, and biological evaluation of pyridazine-based, 4-bicyclic heteroaryl-piperidine derivatives as potent stearoyl-CoA desaturase-1 (SCD1) inhibitors are described. In a chronic study of selected analog (3e) in Zucker fa/fa (ZF) rat, dose-dependent decrease of body weight gain and plasma fatty acid desaturation index (DI) in both C16 and C18 are also demonstrated. The results indicate that the plasma fatty acid DI may serve as an indicator for direct target engagement and biomarker for SCD1 inhibition.

KEYWORDS:

Desaturation index; SCD1 inhibitors; Stearoyl-CoA desaturase; obesity

PMID:
24405703
DOI:
10.1016/j.bmcl.2013.12.075
[PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Chemical Information

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center