New CCK antagonists derived from the amino acid residues of the CCK-8 fragment

Farmaco. 1991 Jan;46(1):45-62.

Abstract

The synthesis of lipophylic derivatives of the amino acid residues of the CCK-8 fragment is described. According to "in vitro" binding studies and functional test, nearly all the compounds behaves as CCK-antagonists; moreover some compounds are able to interact differentially with CCK-A and CCK-B receptor subtype. In particular, compounds 2c, 2g, and 2h possess a high affinity for the CCK-A receptor subtype coupled with a low affinity for the CCK-B subtype. This results in an interesting selectivity profile. However, the same compounds are not able to antagonize the effects exerted by CCK-itself, when tested in "in vivo" assays.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain Chemistry / drug effects
  • Cholecystokinin / antagonists & inhibitors*
  • Female
  • Gallbladder / drug effects
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Mice
  • Molecular Sequence Data
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Pyrazines / chemical synthesis*
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Sincalide / analogs & derivatives*
  • Sincalide / pharmacology
  • Thiones / chemical synthesis
  • Thiones / pharmacology
  • Thiones / therapeutic use
  • Thiophenes
  • Vinyl Compounds / chemical synthesis*
  • Vinyl Compounds / pharmacology
  • Vinyl Compounds / therapeutic use

Substances

  • Pyrazines
  • Receptors, Cholecystokinin
  • Thiones
  • Thiophenes
  • Vinyl Compounds
  • oltipraz
  • Cholecystokinin
  • Sincalide