THE DISCOVERY OF (2S,3S)-CIS-2-(DIPHENYLMETHYL)-N-[(2-METHOXYPHENYL)METHYL]-1-AZABICYCLO[2.2.2]OCTAN-3-AMINE AS A NOVEL, NONPEPTIDE SUBSTANCE-P ANTAGONIST

被引：121

作者：

LOWE, JA

DROZDA, SE

SNIDER, RM

LONGO, KP

ZORN, SH

MORRONE, J

JACKSON, ER

MCLEAN, S

BRYCE, DK

BORDNER, J

NAGAHISA, A

KANAI, Y

SUGA, O

TSUCHIYA, M

机构：

[1] Department of Exploratory Medicinal Chemistry, Central Research Division, Pfizer Inc., Groton

[2] Department of Medicinal Biology, Central Research Division, Pfizer Inc., Aichi 470-23

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 14期

关键词：

D O I：

10.1021/jm00092a009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe the structure-activity relationship development of a series of quinuclidines which culminated in the first potent, selective, nonpeptide substance P (SP) antagonist, (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxy-phenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine, 3 (CP-96,345). Compound 3 is a potent displacer of [H-3]SP binding in human IM-9 cells and blocks SP-induced and capsaicin-induced plasma extravasation, as well as SP-induced salivation in the rat in vivo. This compound may both help to further our understanding of the interactions of small molecules with peptide receptors and serve to evaluate the therapeutic potential of a SP antagonist.

引用

页码：2591 / 2600

页数：10

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