New CCK antagonists derived from the amino acid residues of the CCK-8 fragment.
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.
Cereda
E
E
Department of Medicinal Chemistry, Istituto de Angeli, Milano.
Bellora
E
E
Ezhayra
A
A
Monferini
E
E
Schiavone
A
A
Volontè
M
M
Donetti
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D005260:Female; D005704:Gallbladder / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013871:Thiones / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D011719:Pyrazines; D011949:Receptors, Cholecystokinin; D013871:Thiones; D013876:Thiophenes; D014753:Vinyl Compounds; C026209:oltipraz; D002766:Cholecystokinin; D012844:Sincalide