Journal of Medicinal Chemistry p. 164 - 168 (1988)
Update date:2022-07-30
Topics:
Ringdahl
Dimethylsulfonium (6a and 6b) and thiolanium analogues (7a and 7b) of oxotremorine were synthesized and found to be potent muscarinic agents in vivo and in vitro. Compound 6a exceeded oxotremorine in potency. Their affinities for muscarinic receptors in the guinea pig ileum and urinary bladder, estimated pharmacologically, were higher than those of the corresponding trimethylammonium (8a and 8b) and N-methylpyrrolidinium compounds (9a and 9b). However, the new compounds had lower intrinsic efficacies than their quaternary ammonium analogues. The compounds also had high affinity for central muscarinic receptors as measured by displacement of specifically bound (-)-[3H]-N-methylscopolamine from homogenates of the rat cerebral cortex. Half-maximal occupation of cortical muscarinic receptors by 6a, 6b, 7a, and 7b was achieved at concentrations of 0.8, 5.4, 0.3, and 3.3 μM, respectively. The competition curves of 6a, 6b, and 7a were adequately described by a two-site binding equation. The ratio of low- and high-affinity dissociation constants agreed with relative efficacy estimated on the ileum. The thiolanium salt 7a was a fairly potent nicotinic agent on the frog rectus abdominis.
View MoreShandong Ailitong New Material Co.,Ltd
Contact:+86-536-3226266
Address:zhongjia village, putong town , qingzhou city,Shandong Province,China
Zhengzhou Yuanli Biological Technology Co., Ltd.
Contact:+86-371-67897870/67897895
Address:No. 38, Qingyang Street, Zhengzhou, Henan, China
Hunan Warrant Chiral Pharmaceutical Co., Ltd.
website:http://www.hwcpharm.com
Contact:+86-0731-85910593
Address:LuTian Road No.28
YingYing Pharmaceutical Co.,Ltd
Contact:86-18854126208
Address:55#, yingxiongshan road
Goldwills Pharmaceuticals Co., Ltd.
Contact:0916-2237889 13991621155
Address:North Suburb of Hanzhong city, Shaanxi Province
Doi:10.1021/ic051289u
(2006)Doi:10.1055/s-0036-1588936
(2017)Doi:10.1007/BF00941104
()Doi:10.1055/s-2004-820033
(2004)Doi:10.1021/jp049641x
(2004)Doi:10.1139/V06-129
(2006)