Studies on antianaphylactic agents. 7. Synthesis of antiallergic 5-oxo-5H-[1]benzopyrano[2,3-b]pyridines

J Med Chem. 1985 May;28(5):559-68. doi: 10.1021/jm50001a005.


5-Oxo-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxylic acids 23 and their tetrazole analogues 24 were synthesized from 4-oxo-4H-1-benzopyran-3-carbonitriles 3 or 2-amino-4-oxo-4H-1-benzopyran-3-carboxaldehydes 4. When administered intravenously, they exhibited antiallergic activity in a reaginic PCA test in rats. In the carboxylic acid series, the activity was influenced by the substituents at the 2-position and increased substantially in the following order: Me, OMe less than NH2 less than OH, H less than NHOMe. On the other hand, in the tetrazole series, 2-unsubstituted derivatives showed the highest activity. Regardless of the kinds of substituents at positions 2 and 3, compounds bearing an alkyl group, especially an isopropyl group at the 7-position, were superior in activity to the corresponding unsubstituted compounds. Among these alkyl derivatives, 3-carboxylic acid derivatives, i.e., 23c (7-ethyl), 23g (2-amino-7-isopropyl), 23r [2-(methoxyamino)-7-isopropyl], and a 3-tetrazole derivative 24c (7-isopropyl), were 41-184 times as potent as disodium cromoglycate. They also exhibited remarkable activity when administered orally; clinical studies on 23g (AA-673) are in progress.

MeSH terms

  • Animals
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / pharmacology
  • Guinea Pigs
  • Hypersensitivity / drug therapy*
  • In Vitro Techniques
  • Lung / drug effects
  • Lung / immunology
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Passive Cutaneous Anaphylaxis / drug effects*
  • Pyridines / chemical synthesis
  • Pyridines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • SRS-A / antagonists & inhibitors
  • SRS-A / biosynthesis
  • Structure-Activity Relationship


  • Benzopyrans
  • Pyridines
  • SRS-A