Journal of Medicinal Chemistry p. 38 - 47 (1992)
Update date:2022-08-03
Topics:
De Costa
Radesca
Di Paolo
Bowen
By synthesizing and testing a part-structure, N-[2-(3,4- dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3), derived from our previously reported high affinity σ receptor ligands (1S,2R)-(-)-N-[2- (3,4-dichlorophenyl)-ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine [(-)- 2] and (+)-2, we have identified a novel class of superpotent (subnanomolar affinity) σ ligands specific for the σ receptor labeled by [3H]-(+)-3-PPP. When 3 was tested for its capacity to displace [3H]-(+)-3-PPP from guinea pig brain membranes, it exhibited a K(i) of 0.34 nM, which is better than either of its parent compounds (-)-2 (K(i) = 1.3 nM) and (+)-2 (K(i) = 6.0 nM). Other compounds related to 3 such as N-[2-(3,4-dichlorophenyl)ethyl]-N- methyl-2-(1-homopiperidinyl)ethylamine (19) exhibited K(i) = 0.17 nM ([3H]- (+)-3-PPP). The determinants for high σ receptor affinity of 3 were examined by manipulation of this structure in a number of different ways. The high efficacy of these compounds for the σ receptor, their relative chemical simplicity and ease of synthesis, and their high degree of selectivity identifies N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1- pyrrolidinyl)ethylamine (3) and related compounds as a highly promising base for determination of the functional role of σ receptors as well as the development of novel therapeutic agents.
View MoreSuzhou Sibian Chemical Technology Co., Ltd
website:http://www.sibianpharm.com
Contact:+8618169181984,+8618013186906
Address:Room1404,BuildingA,Jiabao Square No.323 Baodai East Road,Wuzhong District,Suzhou Jiangsu China (215128)
Nantong LiKai Chemical Co.,Ltd
Contact:+86-513-89068669
Address:Jincheng Science Park
Valiant Fine Chemicals Co., Ltd.
Contact:+86 535 6101878/6374484
Address:11 Wuzhishan Rd.,YTETDZ,Yantai,264006,Shandong,China
Tianjin Emulsion Science&Technology Development Co.,Ltd
Contact:13901380442
Address:Vake Garden New Town New Yi Bai Road Beichen District Tianjin,China
website:http://www.chinabarton.com
Contact:+86-573-82719618
Address:No. 162 Fumin Road, Honghe Town,
Doi:10.1021/jm00088a019
(1992)Doi:10.1039/c2ob25543j
(2012)Doi:10.1039/c2cc33339b
(2012)Doi:10.1021/jo00816a600
(1971)Doi:10.1080/10426509908546463
(1999)Doi:10.1246/cl.2003.322
(2003)