Identification of nonabsorbable inhibitors of the scavenger receptor-BI (SR-BI) for tissue-specific administration

Bioorg Med Chem Lett. 2016 Apr 15;26(8):1901-4. doi: 10.1016/j.bmcl.2016.03.025. Epub 2016 Mar 9.

Abstract

The identification of a low-permeability scavenger receptor BI (SR-BI) inhibitor starting from the ITX-5061 template is described. Structure-activity and structure-permeability relationships were assessed for analogs leading to the identification of compound 8 as a potent and nonabsorbable SR-BI inhibitor.

Keywords: Intestinal SR-BI; Nonabsorbed SR-BI inhibitor; SR-BI inhibitor; Scavenger receptor class B type I.

MeSH terms

  • Animals
  • Dogs
  • Dose-Response Relationship, Drug
  • Humans
  • Madin Darby Canine Kidney Cells
  • Molecular Structure
  • Organ Specificity
  • Phenylenediamines / administration & dosage
  • Phenylenediamines / chemistry
  • Phenylenediamines / pharmacology*
  • Rats
  • Scavenger Receptors, Class B / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Sulfonamides / administration & dosage
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • ITX-5061
  • Phenylenediamines
  • SCARB1 protein, human
  • Scarb1 protein, rat
  • Scavenger Receptors, Class B
  • Sulfonamides