3-(2-aminoalkyl)-1-(2,6-difluorobenzyl)-5- (2-fluoro-3-methoxyphenyl)-6-methyl-uracils as orally bioavailable antagonists of the human gonadotropin releasing hormone receptor

J Med Chem. 2004 Jul 1;47(14):3483-6. doi: 10.1021/jm049791w.

Abstract

Uracils possessing N-3 side chains derived from various amino alcohols were designed and synthesized as potent human gonadotropin releasing hormone receptor antagonists. The compounds herein presented displayed superior metabolic stability than their predecessor molecules. Selected compounds from this series featured good oral bioavailability in mice and cynomolgus monkeys.

Publication types

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

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Humans
  • Macaca fascicularis
  • Mice
  • Receptors, LH / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Uracil / analogs & derivatives*
  • Uracil / chemical synthesis*
  • Uracil / pharmacology

Substances

  • Receptors, LH
  • Uracil