Selective thromboxane synthetase inhibitors and antihypertensive agents. New derivatives of 4-hydrazino-5H-pyridazino[4,5-b]indole, 4-hydrazinopyridazino[4,5-a]indole, and related compounds

J Med Chem. 1987 Jun;30(6):1029-35. doi: 10.1021/jm00389a012.

Abstract

A series of new derivatives of 4-hydrazino-5H-pyridazino[4,5-b]indole (5) and 4-hydrazinopyridazino[4,5-a]indole (12) have been synthesized to investigate their activities as selective thromboxane synthetase inhibitors as well as antihypertensive agents. Several of the prepared compounds were found to be selective thromboxane synthetase inhibitors, in concordance with the Gorman model. The most potent were 8-(benzyloxy)-3,4-dihydro-4-oxo-5H-pyridazino[4,5-b]indole (3c) and 8-methoxy-4-hydrazino-5H-pyridazino[4,5-b]indole (5). This last compound did not inhibit prostacyclin formation and showed an antihypertensive activity similar to that of hydralazine. The acute toxicity in mice for 5a . HCl is about 2.2 times less than that for hydralazine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / chemical synthesis*
  • Antihypertensive Agents / pharmacology
  • Female
  • Guinea Pigs
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Male
  • Platelet Aggregation / drug effects
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred Strains
  • Structure-Activity Relationship
  • Thromboxane-A Synthase / antagonists & inhibitors*

Substances

  • Antihypertensive Agents
  • Indoles
  • Pyridines
  • Thromboxane-A Synthase