Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of [beta-(Aroylamino)ethyl]piperazines and -piperidines and [2-[(Arylamino)carbonyl]ethyl]piperazines, -pyrazinopyridoindoles, and -pyrazinoisoquinolines. A new class of potent H1 antagonists

J Med Chem. 1990 Nov;33(11):2970-6. doi: 10.1021/jm00173a011.

Abstract

Some [beta-(Aroylamino)ethyl]piperazines and -piperidines and [2-[(Arylamino)carbonyl]ethyl]piperazines, -piperidines, -pyrazinopyridoindoles, and -pyrazinoisoquinolines have been synthesized and their H1-antagonistic activity studied in isolated guinea pig ileum. Quantitative structure-activity relationship analysis indicates that the hydrophobicity of the side chain of these compounds plays a major role in their activity while steric and electronic factors are of secondary importance. All these compounds act on a common receptor and appear to interact similarly with the receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology
  • Animals
  • Guinea Pigs
  • Histamine / pharmacology
  • Histamine H1 Antagonists / chemical synthesis*
  • Histamine H1 Antagonists / chemistry
  • Histamine H1 Antagonists / pharmacology
  • Ileum / drug effects
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology
  • Molecular Structure
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Structure-Activity Relationship

Substances

  • Amines
  • Histamine H1 Antagonists
  • Indoles
  • Isoquinolines
  • Piperazines
  • Piperidines
  • Histamine