Synthesis and β-adrenergic blocking activity of oxime ether hybrids derived from a natural isochroman-4-one

Chin J Nat Med. 2013 Sep;11(5):538-45. doi: 10.1016/S1875-5364(13)60098-9.

Abstract

Aim: In a search for new cardiovascular drug candidates, a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized.

Method: Compounds 3 and 6, derived from the natural antihypertensive compound 7, 8-dihydroxy-3-methyl-isochroman-4-one (XJP), were designed and synthesized. Subsequently, a series of novel isochroman-4-one oxime ether hybrids were prepared by hybridizing various N-substituted isopropanolamine functionalities to isochroman-4-one oxime. Furthermore, β1-adrenergic blocking activities of the synthesized compounds were assayed using the isolated rat left atria.

Results: Twenty target compounds were obtained, and the preliminary structure-activity relationships were deduced. The most promising compound Ic exhibited β1-adrenoceptor blocking activity (inhibition: 52.2%) at 10(-7) mol·L(-1), which was superior to that of propranolol (inhibition: 49.7%).

Conclusion: The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.

Keywords: Antihypertensive activity; Hybrids; Isochroman-4-one derivatives; Oxime ethers; β-Adrenergic blocking activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / chemical synthesis*
  • Adrenergic beta-Antagonists / chemistry
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Antihypertensive Agents / chemical synthesis
  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / pharmacology
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology*
  • Drugs, Chinese Herbal / chemical synthesis*
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Molecular Structure
  • Oximes / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • 7,8-dihydroxy-3-methylisochroman-4-one
  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Benzopyrans
  • Drugs, Chinese Herbal
  • Oximes