Synthesis and structure-activity relationship of new 1,5-dialkyl-1,5-benzodiazepines as cholecystokinin-2 receptor antagonists

被引：11

作者：

Roberts, Karen ^{[1
]}

Ursini, Antonella ^{[1
]}

Barnaby, Robert ^{[1
]}

Cassara, Paolo G. ^{[1
]}

Corsi, Mauro ^{[1
]}

Curotto, Giovanni ^{[1
]}

Donati, Daniele ^{[1
]}

Feriani, Aldo ^{[1
]}

Finizia, Gabriella ^{[1
]}

Marchioro, Carla ^{[1
]}

Niccolai, Daniela ^{[1
]}

Oliosi, Beatrice ^{[1
]}

Polinelli, Stefano ^{[1
]}

Ratti, Emiliangelo ^{[1
]}

Reggiani, Angelo ^{[1
]}

Tedesco, Giovanna ^{[1
]}

Tranquillini, Maria E. ^{[1
]}

Trist, David G. ^{[1
]}

van Amsterdam, Franciscus T. M. ^{[1
]}

机构：

[1] GlaxoSmithKline, Med Res Ctr, I-37100 Verona, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 14期

关键词：

1,5-Benzodiazepine; Cholecystokinin; CCK2; antagonists; Anxiety; CCK-B ANTAGONISTS; GASTRIN; POTENT; ANALOGS; BRAIN; 1,5-BENZODIAZEPINES; DERIVATIVES; RESOLUTION; LIGANDS; SUBSTITUTION;

D O I：

10.1016/j.bmc.2011.05.057

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureido-1,5-benzodiazepin-2,4-diones which were prepared as potential CCK2 antagonists, with the intention to find a possible follow up of our lead compound GV150013, showing an improved pharmacokinetic profile. The phenyl ring at N-5 was replaced with more hydrophilic substituents, like alkyl groups bearing basic functions. In some cases, the resolution of the racemic key intermediates 3-amino-benzodiazepines was also accomplished. Among the compounds synthesized and characterised so far in this class, the 5-morpholinoethyl derivative 54, was selected as potential follow up of GV150013 and submitted for further evaluation. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：4257 / 4273

页数：17

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