Design and synthesis of m1-selective muscarinic agonists:: (R)-(-)-(Z)-1-azabicyclo[2.2.1]heptan-3-one, O-(3-(3′-methoxyphenyl)-2-propynyl)oxime maleate (CI-1017), a functionally m1-selective muscarinic agonist

被引：30

作者：

Tecle, H ^{[1
]}

Barrett, SD

Lauffer, DJ

Augelli-Szafran, C

Brann, MR

Callahan, MJ

Caprathe, BW

Davis, RE

Doyle, PD

Eubanks, D

Lipiniski, W

Mirzadegan, T

Moos, WH

Moreland, DW

Nelson, CB

Pavia, MR

Raby, C

Schwarz, RD

Spencer, CJ

Thomas, AJ

Jaen, JC

机构：

[1] Parke Davis Pharmaceut Res, Ann Arbor, MI 48106 USA

[2] Receptor Technol Inc, Winooski, VT 05404 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 14期

关键词：

D O I：

10.1021/jm960683m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one, O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of 24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an mi-selective muscarinic agonist. Efficacy and mi selectivity reside in the R enantiomer, (R)-24Z (CI-1017).

引用

页码：2524 / 2536

页数：13

共 56 条

[1]

BAKER R, 1989, ANNU REP MED CHEM, V24, P31

[2] SYNTHESIS, PHYSICOCHEMICAL AND CONFORMATIONAL PROPERTIES OF (3R,4R)-3-(3-CYCLOPROPYL-1,2,4-OXADIAZOL-5-YL)-1-AZABICYCLO[2.2.1]HEPTANE, A NOVEL M(1) SELECTIVE MUSCARINIC PARTIAL AGONIST [J].