Design, synthesis and cardiovascular evaluation of some aminoisopropanoloxy derivatives of xanthone

Bioorg Med Chem. 2018 Jul 30;26(13):3773-3784. doi: 10.1016/j.bmc.2018.04.038. Epub 2018 Apr 18.

Abstract

A series of aminoisopropanoloxy derivatives of xanthone has been synthesized and their pharmacological properties regarding the cardiovascular system has been evaluated. Radioligand binding and functional studies in isolated organs revealed that title compounds present high affinity and antagonistic potency for α1-(compound 2 and 8), β-(compounds 1, 3, 4, 7), α1/β-(compounds 5 and 6) adrenoceptors. Furthermore, compound 7, the structural analogue of verapamil, possesses calcium entry blocking activity. The title compounds showed hypotensive and antiarrhythmic properties due to their adrenoceptor blocking effect. Moreover, they did not affect QRS and QT intervals, and they did not have proarrhythmic potential at tested doses. In addition they exerted anti-aggregation effect. The results of this study suggest that new compounds with multidirectional activity in cardiovascular system might be found in the group of xanthone derivatives.

Keywords: Adrenoceptor; Arrhythmia; Cardiovascular; Hypertension; Synthesis; Xanthone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / chemical synthesis*
  • Adrenergic Antagonists / metabolism
  • Adrenergic Antagonists / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / chemical synthesis
  • Calcium Channel Blockers / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / chemistry
  • Calcium Channels / metabolism
  • Drug Design*
  • Heart Rate / drug effects
  • Inhibitory Concentration 50
  • Male
  • Platelet Aggregation / drug effects
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha / chemistry
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Adrenergic, beta / chemistry
  • Receptors, Adrenergic, beta / metabolism
  • Structure-Activity Relationship
  • Verapamil / chemistry
  • Xanthones / chemistry*
  • Xanthones / metabolism
  • Xanthones / pharmacology

Substances

  • Adrenergic Antagonists
  • Calcium Channel Blockers
  • Calcium Channels
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Xanthones
  • xanthone
  • Verapamil