1,2,3,4-Tetrahydroquinoline-containing alphaVbeta3 integrin antagonists with enhanced oral bioavailability

Bioorg Med Chem Lett. 2004 Dec 6;14(23):5937-41. doi: 10.1016/j.bmcl.2004.08.067.

Abstract

Reduction of the quinoline ring in an alpha(v)beta(3) antagonist yielded a 1,2,3,4-tetrahydro derivative as two diastereomers, the four isomers of which were separated by sequential chiral HPLC. Two isomers had significant alpha(V)beta(3) antagonist activity with improved oral bioavailability, relative to the corresponding quinoline derivative.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Integrin alphaVbeta3 / metabolism*
  • Quinolines / administration & dosage
  • Quinolines / chemistry*
  • Quinolines / metabolism*
  • Rats

Substances

  • Integrin alphaVbeta3
  • Quinolines