Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors

Bioorg Med Chem Lett. 2011 Aug 15;21(16):4762-7. doi: 10.1016/j.bmcl.2011.06.067. Epub 2011 Jun 29.

Abstract

A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Fructokinases / antagonists & inhibitors*
  • Indazoles / chemical synthesis
  • Indazoles / chemistry
  • Indazoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Pyrazoles / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Indazoles
  • Pyrazoles
  • pyrazole
  • Fructokinases
  • ketohexokinase