Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers

Bioorg Med Chem Lett. 2005 May 16;15(10):2519-22. doi: 10.1016/j.bmcl.2005.03.057.

Abstract

Uracil derivatives were designed and synthesized to avoid atropisomers observed in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at the 1- and 5-positions of the uracil resulted in potent compounds such as 24 (Ki=0.45 nM).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Humans
  • Isomerism
  • Molecular Structure
  • Receptors, LHRH / antagonists & inhibitors*
  • Uracil / chemistry
  • Uracil / pharmacology*
  • X-Ray Diffraction

Substances

  • Receptors, LHRH
  • Uracil