2. Academic Validation
  3. Imidazopyridine and Pyrazolopiperidine Derivatives as Novel Inhibitors of Serine Palmitoyl Transferase

Imidazopyridine and Pyrazolopiperidine Derivatives as Novel Inhibitors of Serine Palmitoyl Transferase

  • J Med Chem. 2016 Jun 23;59(12):5904-10. doi: 10.1021/acs.jmedchem.5b01851.
Michael J Genin 1,  Isabel C Gonzalez Valcarcel 1,  William G Holloway 1,  Jason Lamar 1,  Marian Mosior 1,  Eric Hawkins 1,  Thomas Estridge 1,  Jeffrey Weidner 1,  Thomas Seng 1,  David Yurek 1,  Lisa A Adams 1,  Jennifer Weller 1,  Vincent L Reynolds 1,  Joseph T Brozinick 1
Affiliations

Affiliation

  • 1 Discovery Chemistry Research and Technology, ‡Cardiovascular and Metabolic Diseases Therapeutic Area, §Diabetes Therapeutic Area, ∥Drug Disposition and Metabolism, ⊥Quantitative Biology, and #Non-Clinical Safety, Lilly Research Laboratories, a Division of Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
PMID: 27213958 DOI: 10.1021/acs.jmedchem.5b01851
Abstract

To develop novel treatments for type 2 diabetes and dyslipidemia, we pursued inhibitors of serine palmitoyl transferase (SPT). To this end compounds 1 and 2 were developed as potent SPT inhibitors in vitro. 1 and 2 reduce plasma ceramides in rodents, have a slight trend toward enhanced Insulin sensitization in DIO mice, and reduce triglycerides and raise HDL in Cholesterol/cholic acid fed rats. Unfortunately these molecules cause a gastric enteropathy after chronic dosing in rats.

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