Journal of Medicinal Chemistry p. 159 - 173 (2019)
Update date:2022-08-15
Topics:
Li, Yuanheng
Sun, Lilan
Yang, Taoyi
Jiao, Wenxuan
Tang, Jingshu
Huang, Xiaomin
Huang, Zongze
Meng, Ying
Luo, Laichun
Wang, Xintong
Bian, Xiling
Zhang, Fang
Wang, Kewei
Sun, Qi
A series of novel thiazolo[4,5-d]pyrimidin-7(6H)-ones (3aa-3eq) were designed, synthesized, and evaluated as the type I positive allosteric modulators of human α7 nAChR expressed in Xenopus ooctyes by a two-electrode voltage clamp. The structure-activity relationship analysis identified the compound 3ea as a potent and efficacious PAM with the maximum activation effect of the α7 current of over 1633% in the presence of acetylcholine (100 μM) and an EC50 = 1.26 μM. It is highly specific to α7 nAChR over other subtypes of nAChR, 5-HT3A, NMDA, and GABAA receptors. Compound 3ea showed an elimination half-life of 10.8 ± 1.5 h for 3 mg/kg, i.v., and 7.4 ± 1.1 h for 60 mg/kg, i.g. in rat. It also exhibited sufficient blood-brain barrier penetration with no significant effect on hERG channel. Most importantly, compound 3ea dose-dependently (0.1-1 mg/kg, i.p.) reversed the prepulse inhibition deficit induced by MK-801 in the mouse schizophrenia model.
View MoreContact:86-510-82853889
Address:Rm.3732, No.18-2,Yonghe Rd.,Wuxi,Jiangsu,214023,China
SHANDONG CREDAGRI CHEMICAL CO., LTD.
Contact:+86-531-88872050
Address:ROOM 601A, BUILDING 2, SHUNTAI SQUARE, NO. 2000 SHUNHUA ROAD, HI-TECH DEVELOPMENT ZONE, JINAN, CHINA.
taicang liyuan chemical co,.ltd
website:http://www.tcliyuanchem.com/productse.php
Contact:86-512-53539583
Address:Room 804,Huaxu Building,No.95,Renmin South Road,Taicang city,Jiangsu Province,China
Shanghai Coupling Pharmaceutical R&D Co., Ltd.(expird)
Contact:+86 021 50106671
Address:403 Room No.4 Buiding, No. 526 Ruiqing Road, Shanghai Zhangjiang Hi-Tech Park
RongCheng Tianyu Technology Co.,Ltd.
Contact:86-631-7519595
Address:220Ping Donghai Road RongChengCity,ShangDong Province China
Doi:10.3390/biom10081101
(2020)Doi:10.1002/1522-2675(20011017)84:10<2924::AID-HLCA2924>3.0.CO;2-E
(2001)Doi:10.1055/s-2001-18065
(2001)Doi:10.1016/S0039-128X(01)00134-9
(2002)Doi:10.1021/ja010493n
(2002)Doi:10.1021/ic010512u
(2002)