Synthesis and structure-activity relationships of antiallergic N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanamides possessing both antihistaminic and anti slow-reacting substance (SRS) activities

Chem Pharm Bull (Tokyo). 1994 Sep;42(9):1822-7. doi: 10.1248/cpb.42.1822.

Abstract

A series of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanamide derivatives were synthesized and tested for in vivo antianaphylactic activity and in vitro anti slow-reacting substance (SRS) activity. Among the compounds synthesized, N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2- thiazolyl]propanamide (7) was the best balanced compound (antianaphylactic activity, ED50 = 0.92 mg/kg p.o.; anti-SRS activity, IC50 = 0.89 microgram/ml). Regarding the biological activities of 7, we ascribe the antianaphylactic activity to its potent antihistaminic activity and the anti SRS activity to the inhibition of 5-lipoxygenase.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / pharmacology*
  • Animals
  • Guinea Pigs
  • Histamine Antagonists / chemical synthesis*
  • Histamine Antagonists / pharmacology*
  • Hypersensitivity / drug therapy*
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • SRS-A / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology*

Substances

  • Amides
  • Histamine Antagonists
  • Indoles
  • SRS-A
  • Thiazoles