Journal of Medicinal Chemistry p. 295 - 305 (1992)
Update date:2022-08-04
Topics:
Street
Baker
Book
Reeve
Saunders
Willson
Marwood
Patel
Freedman
The synthesis and cortical muscarinic activity of a novel series of pyrazine-based agonists is described. Quinuclidine and azanorbornane derivatives were prepared either by reaction of lithiated pyrazines with azabicyclic ketones, followed by chlorination and reduction, or by reaction of the lithium enolate of the azabicyclic ester with 2-chloropyrazines followed by ester hydrolysis and decarboxylation. Substitution at all three positions of the heteroaromatic ring has been explored. Optimal muscarinic agonist activity was observed for unsubstituted pyrazines in the azanorbornane series. The exo-1-azanorbornane 18a is one of the most efficacious and potent centrally active muscarinic agonists known. Studies on the 3-substituted derivatives have provided evidence of the preferred conformation of these ligands for optimal muscarinic activity. Substitution at C6 gave ligands with increased affinity and reduced efficacy. Moving the position of the diazine ring nitrogens to give pyrimidine and pyridazine derivatives resulted in a significant loss of muscarinic activity.
View MoreJiangsu Hualun Chemical Industry Co., Ltd
website:http://www.hualunchem.com
Contact:+86-0514-86464168 86507985
Address:39# Middle Renmin Road, Dinghuo Town
website:http://www.antaibio.com
Contact:86-21-60939051,60939771
Address:1518#,ZHANGYANG ROAD
shanghai Tauto Biotech Co., Ltd
website:http://www.tautobiotech.com/en/index.htm
Contact:+86-21-51320588 ext. 8025
Address:No. 326, Aidisheng Rd , Zhangjiang Hi-tech Park, Shanghai , P.R.CHINA
website:http://www.angchenchem.com
Contact:+86-510-88302099 82327577
Address:Rm. 404/405, Floor 4th, No. 983 FengXiang Road, Wuxi, China
Shandong Yuanli Science and Technology Co., Ltd.
Contact:86-0536-6777557
Address:Zhuliu Industiral Park,Changle County
Doi:10.1016/j.tetlet.2012.06.083
(2012)Doi:10.1021/ol302032w
(2012)Doi:10.1002/anie.201409983
()Doi:10.1021/jo016058t
(2001)Doi:10.1016/j.tetlet.2013.08.096
(2013)Doi:10.1007/s10895-010-0679-0
(2010)