1053644-74-8Relevant academic research and scientific papers
Synthesis and stereochemical structure activity relationships of 1,3- dioxoperhydropyrido[1,2-c]pyrimidine derivatives: Potent and selective cholecystokinin-a receptor antagonists
Martín-Martínez, Mercedes,Bartolomé-Nebreda, José M.,Gómez-Monterrey, Isabel,González-Mu?iz, Rosario,Garc?a-L?pez, M. Teresa,Ballaz, Santiago,Barber, Ana,Fortu?o, Ana,Del Río, Joaquín,Herranz, Rosario
, p. 3402 - 3407 (1997)
The synthesis and stereochemical structure-activity relationships of a new class of potent and selective non-peptide cholecystokinin-A (CCK-A) receptor antagonists based on the 1,3-dioxoperhydropyrido[1,2-c]pyrimidine skeleton are described. The most potent member of this series of eight diastereoisomers, (4aS,5R)-2-benzyl-5-[N-[(tert-butoxycarbonyl)-L- tryptophyl]-amino]-1,3-dioxoperhydropyrido[1,2-c]pyrimidine, displays nanomolar CCK-A receptor affinity and higher than 8000-fold potency at the CCK-A than at the CCK-B receptor. As CCK-A antagonist, this compound inhibits the CCK-8-evoked amylase release from pancreatic acinar cells at a low concentration, similar to that of the typical antagonist Devazepide. Highly strict stereochemical requirements for CCK-A receptor binding and selectivity have been found. The L-Trp and the 4a,5-trans disposition of the bicyclic perhydropyrido[1,2-c]pyrimidine are essential for binding potency and selectivity.
