Replacement of amide with bioisosteres led to a new series of potent adenosine A2A receptor antagonists

Bioorg Med Chem Lett. 2014 Jan 1;24(1):152-5. doi: 10.1016/j.bmcl.2013.11.051. Epub 2013 Dec 1.

Abstract

We have previously reported a series of 2,4,6-trisubstituted pyrimidines as potent A2A receptor antagonists. The leading compounds often feature a potentially labile acetamide functional group which tends to hydrolyze under acidic conditions. Here we report the replacement of the acetamide functional group with bioisosteres. This effort led us to a new series of adenosine A2A receptor antagonists with improved potency and chemical stability.

Keywords: Adenosine receptor; Antagonist; Bioisostere; GPCR; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemistry*
  • Adenosine A2 Receptor Antagonists / chemical synthesis
  • Adenosine A2 Receptor Antagonists / chemistry
  • Adenosine A2 Receptor Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Receptor, Adenosine A2A / metabolism*
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Adenosine A2 Receptor Antagonists
  • Pyrimidines
  • Receptor, Adenosine A2A
  • acetamide