Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha2-adrenoceptor antagonistic activities. Part 2: Further exploration on the cinnamyl moiety

Bioorg Med Chem Lett. 2004 Jun 7;14(11):2917-22. doi: 10.1016/j.bmcl.2004.03.031.

Abstract

In our previous paper we have described the synthesis of a series of 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, as novel dual 5-HT reuptake inhibitors and alpha2-adrenoceptor antagonists. That investigation led to the identification of the cinnamyl fragment as the most suitable moiety for combined activity. This paper outlines a further optimisation programme, focused on the exploration of the aromatic ring present on the cinnamyl moiety of compounds 1, 2 and 3.

MeSH terms

  • Adrenergic Antagonists / chemical synthesis*
  • Adrenergic Antagonists / pharmacology
  • Adrenergic alpha-2 Receptor Antagonists
  • Cinnamates / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Isoxazoles / chemical synthesis
  • Isoxazoles / pharmacology*
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Adrenergic Antagonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Cinnamates
  • Isoxazoles
  • Serotonin Uptake Inhibitors