5-PHENYL-3-UREIDOBENZAZEPIN-2-ONES AS CHOLECYSTOKININ-B RECEPTOR ANTAGONISTS

被引：67

作者：

LOWE, JA

HAGEMAN, DL

DROZDA, SE

MCLEAN, S

BRYCE, DK

CRAWFORD, RT

ZORN, S

MORRONE, J

BORDNER, J

机构：

[1] Central Research Division, Pfizer Inc., Connecticut 06340, Eastern Point Road, Groton

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 22期

关键词：

D O I：

10.1021/jm00048a015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 5-phenyl-3-ureidobenzazepin-2-one cholecystokinin-B (CCK-B) receptor antagonists was synthesized using Beckmann ring expansion of a suitable 4-phenyl-1-tetralone as a key step. Structure-activity relationship studies revealed the importance of the 5-phenyl group for potent and selective CCK-B affinity. Addition of an 8-methyl substituent and resolution provided the potent (CCK-B IC50 = 0.48 nM) CCK-B antagonist 4. The role of the 5-phenyl group as part of a ''privileged structure'' for high-affinity receptor antagonism is discussed.

引用

页码：3789 / 3811

页数：23

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