Synthesis and in vitro evaluation of derivatives of the β₁-adrenergic receptor antagonist HX-CH 44

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5506-9. doi: 10.1016/j.bmcl.2011.06.106. Epub 2011 Jun 30.

Abstract

Isopropyl- and fluoroisopropyl-amino derivatives of the β(1)-adrenergic receptor antagonist 2-[4-[3-(tert-butyl-amino)-2-hydroxypropoxy]phenyl]-3-methyl-6-methoxy-4(3H)-quinazolinone ((±)HX-CH 44) were synthesized, including a concise and efficient preparation of the core, 2-(4-hydroxyphenyl)-6-methoxy-3-methylquinazolin-4(3H)-one. In vitro binding assays showed that the fluorinated analog was selective towards β(1)-adrenergic receptors over β(2)-adrenergic and 5-HT(1A) receptors. An X-ray crystallographic characterization of the fluorinated analog is also reported.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Agonists / chemical synthesis*
  • Adrenergic beta-1 Receptor Agonists / chemistry
  • Adrenergic beta-1 Receptor Agonists / pharmacology*
  • Chemistry Techniques, Synthetic
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Propanolamines / chemical synthesis
  • Propanolamines / chemistry
  • Propanolamines / pharmacology*
  • Quinazolinones / chemical synthesis
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Receptors, Adrenergic, beta-1 / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Adrenergic beta-1 Receptor Agonists
  • Propanolamines
  • Quinazolinones
  • Receptors, Adrenergic, beta-1
  • HX-CH 44BS