Non-imidazole histamine H3 ligands. Part I. Synthesis of 2-(1-piperazinyl)- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazole derivatives as H3-antagonists with H1 blocking activities

Farmaco. 1999 Oct 30;54(10):684-94. doi: 10.1016/s0014-827x(99)00081-6.

Abstract

New 2-(1-Piperazinyl)- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazoles were prepared and tested as H1- and H3-receptor antagonists. A number of compounds showed weak H1-antagonistic activity, with pA2 values ranging from 5.5 to 6.1. The simple alkyl substituted, 2-[1-(4-methyl and 4-ethyl)piperazinyl] analogues show increasing, moderate H3-antagonistic activity (pA2 = 6.0, and pA2 = 7.0). The compounds with 4-phenylalkyl substitution, for both the piperazinyl and the hexahydro-1H-1,4-diazepin-1-yl homologues series, regardless of the different physicochemical properties of the para substituents at the phenyl ring, showed weak H3-antagonistic activity with pA2 values ranging from 4.4 to 5.6.

MeSH terms

  • Animals
  • Guinea Pigs
  • Histamine Antagonists / chemical synthesis*
  • Histamine Antagonists / pharmacology
  • Histamine H1 Antagonists / chemical synthesis*
  • Histamine H1 Antagonists / pharmacology
  • Male
  • Receptors, Histamine H3 / drug effects*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology

Substances

  • Histamine Antagonists
  • Histamine H1 Antagonists
  • Receptors, Histamine H3
  • Thiazoles