Pyrrolidine and piperidine analogues of SC-57461A as potent, orally active inhibitors of leukotriene A(4) hydrolase

Bioorg Med Chem Lett. 2002 Dec 2;12(23):3383-6. doi: 10.1016/s0960-894x(02)00760-6.

Abstract

The synthesis and biological evaluation of a series of functionalized pyrrolidine- and piperidine-containing analogues of our lead LTA(4) hydrolase inhibitor, SC-57461A, is described. A number of compounds showed excellent potency in our in vitro screens and several demonstrated good oral activity in a mouse ex vivo assay. These efforts led to the identification of SC-56938 (14) as a potent, orally active inhibitor of LTA(4) hydrolase.

MeSH terms

  • Administration, Oral
  • Animals
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Piperidines / chemistry*
  • Piperidines / pharmacology*
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacology*
  • Structure-Activity Relationship
  • beta-Alanine / analogs & derivatives*
  • beta-Alanine / chemistry*

Substances

  • Enzyme Inhibitors
  • Piperidines
  • Pyrrolidines
  • SC 57461
  • SC56938
  • beta-Alanine
  • Epoxide Hydrolases
  • leukotriene A4 hydrolase