Selective non-peptide ligands for an accommodating peptide receptor. Imidazobenzodiazepines as potent cholecystokinin type B receptor antagonists.
A series of imidazobenzodiazepines, non-peptide antagonists of the peptide hormone cholecystokinin (CCK), are described. Derived by chemical modification of the benzodiazepine ring system embedded within the CCK-B antagonist L-365,260, these compounds display CCK-B/CCK-A selectivity and some analogs have receptor binding affinities in the subnanomolar range. This group of novel imidazobenzodiazepines, among which N-[(2S,4R)-methyl-6-phenyl-2,4-dihydro-1H-imidazo[1,2- alpha][1,4]benzodiazepin-4-yl]-N'-[3-methylphenyl]-urea (12) is the principal compound, expands the structural diversity of the collection of non-peptide CCK-B antagonists and will be useful in further delineating the function of CCK in the central nervous system.
Bock
M G
MG
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486.
DiPardo
R M
RM
Newton
R C
RC
Bergman
J M
JM
Veber
D F
DF
Freedman
S B
SB
Smith
A J
AJ
Chapman
K L
KL
Patel
S
S
Kemp
J A
JA
D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D007093:Imidazoles; D008024:Ligands; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D001569:Benzodiazepines