Synthesis of (+)-cis-N-(4-isothiocyanatobenzyl)-N-normetazocine, an isothiocyanate derivative of N-benzylnormetazocine as acylant agent for the sigma(1) receptor

J Med Chem. 2002 Jun 6;45(12):2662-5. doi: 10.1021/jm010501a.

Abstract

(+)-cis-N-(4-Isothiocyanatobenzyl)-N-normetazocine (BNIT) (+)-(4) was designed and synthesized as a derivative of the potent and selective sigma(1) receptor ligand (+)-cis-N-benzyl-N-normetazocine for irreversibly blocking sigma(1) binding sites. Pretreatment of guinea pig brain membranes with BNIT (0.1, 1, and 5 microM) caused a concentration-dependent loss of binding of the selective sigma(1) ligand [(3)H]-(+)-pentazocine. Binding experiments with [(3)H]-1,3-di(2-tolyl)guanidine ([(3)H]-DTG), a ligand of sigma(1) and sigma(2) receptors, showed that pretreatment with BNIT blocked only the sigma(1) component of [(3)H]-DTG binding.

MeSH terms

  • Acylation
  • Animals
  • Binding Sites
  • Brain / metabolism
  • Cyclazocine / analogs & derivatives*
  • Cyclazocine / chemical synthesis*
  • Cyclazocine / chemistry*
  • Cyclazocine / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Pentazocine / metabolism
  • Radioligand Assay
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, delta / metabolism
  • Stereoisomerism

Substances

  • N-(4-isothiocyanatobenzyl)-N-normetazocine
  • Receptors, Opioid, delta
  • N-benzylnormetazocine
  • Cyclazocine
  • Pentazocine