Ursini A, Capelli A M, Carr R A, Cassarà P, Corsi M, Curcuruto O, Curotto G, Dal Cin M, Davalli S, Donati D, Feriani A, Finch H, Finizia G, Gaviraghi G, Marien M, Pentassuglia G, Polinelli S, Ratti E, Reggiani A M, Tarzia G, Tedesco G, Tranquillini M E, Trist D G, Van Amsterdam F T
Glaxo Wellcome Medicines Research Centre, Via A. Fleming 4, 37135 Verona, Italy.
J Med Chem. 2000 Oct 5;43(20):3596-613. doi: 10.1021/jm990967h.
A series of 5-phenyl-3-ureidobenzodiazepine-2,4-diones was synthesized and evaluated as cholecystokinin-B (CCK-B) receptor antagonists. Structure-activity relationship (SAR) studies revealed the importance of the N-1 substituent for potent and selective CCK-B affinity. Addition of substituents at the urea side chain provided in some cases more potent compounds. Moreover the introduction of bulky substituents such as adamantylmethyl at N-1 and resolution of the racemic ureas resulted in our lead compound GV150013.
合成了一系列5-苯基-3-脲基苯并二氮杂卓-2,4-二酮，并将其作为胆囊收缩素-B（CCK-B）受体拮抗剂进行评估。构效关系（SAR）研究表明，N-1取代基对于强效和选择性CCK-B亲和力很重要。在脲侧链上添加取代基在某些情况下可提供更强效的化合物。此外，在N-1处引入大体积取代基如金刚烷基甲基并拆分外消旋脲，得到了我们的先导化合物GV150013。
