Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,1-c][1,4]benzoxazines, imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles

J Med Chem. 1988 Jun;31(6):1098-115. doi: 10.1021/jm00401a009.

Abstract

4H-Imidazo[2,1-c][1,4]benzoxazine-2-carboxylic acid (3) was found to possess potent activity in the IgE-induced rat passive cutaneous anaphylaxis model which may be predictive of clinical antiallergic activity. Compared to disodium cromoglycate (DSCG, 1), 3 was less active following iv administration but unlike DSCG showed very significant oral activity. To explore the structural requirements for this activity, a range of tricyclic compounds was prepared and their activities were measured. Individual 2-carboxylic acids derived from imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles showed iv activities up to 10(3) times as potent as DSCG and many of them showed significant oral activity. From these, imidazo[1,2-a]quinoxaline-2-carboxylic acid 114 has been chosen for further development.

MeSH terms

  • Animals
  • Carboxylic Acids / chemical synthesis
  • Cromolyn Sodium / pharmacology
  • Histamine H1 Antagonists / chemical synthesis*
  • Histamine H1 Antagonists / pharmacology
  • Hypersensitivity / drug therapy*
  • Imidazoles / chemical synthesis*
  • Oxazines / chemical synthesis
  • Passive Cutaneous Anaphylaxis / drug effects
  • Pyrroles / chemical synthesis*
  • Quinoxalines / chemical synthesis
  • Rats
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis

Substances

  • Carboxylic Acids
  • Histamine H1 Antagonists
  • Imidazoles
  • Oxazines
  • Pyrroles
  • Quinoxalines
  • Thiazoles
  • imidazo(1,2-a)quinoxaline-2-carboxylic acid
  • Cromolyn Sodium