Journal of Medicinal Chemistry p. 8216 - 8230 (2020)
Update date:2022-09-26
Topics:
Mandal, Mihirbaran
Buevich, Alexei
Caldwell, John P.
Hyde, Lynn
Huang, Xianhai
Liu, Xiaoxiang
Mckittrick, Brian
Mazzola, Robert D.
Pissarnitski, Dmitri
Palani, Anandan
Zhang, Lili
Parker, Eric
Xiao, Li
Rindgen, Diane
Zhu, Zhaoning
Herein, we disclose three structurally differentiated γ-secretase modulators (GSMs) based on an oxadiazine scaffold. The analogues from series I potently inhibit the generation of Aβ42 in vitro when the substituents at 3 and 4 positions of the oxadiazine moiety adopt an α orientation (cf. 11). To address the concern around potential reactivity of the exocyclic double bond present in series I toward nucleophilic attack, compounds containing either an endocyclic double bond, such as 20 (series II), or devoid of an olefinic moiety, such as 27 (series III), were designed and validated as novel GSMs. Compound 11 and azepine 20 exhibit robust lowering of CSF Aβ42 in rats treated with a 30 mg/kg oral dose.
View MoreLeshan Kai Yada Photoelectric Technology Co., Ltd.,
website:http://www.kydmaterials.com
Contact:0833-5603116
Address:Airport road Jiajiang county, Sichuan province,China
Rudong Zhenfeng Yiyang Chemical Co., Ltd.
Contact:0513-84573047
Address:South Fengli Town, Rudong County, Jiangsu Province, China
Compro Shijiazhuang Fine Chemical Co., Ltd
Contact:0086-311-89689838
Address:Economic and Technological Development Zone of Shijiazhuang,Hebei
Nanjing Qirui Material Co., Ltd.
Contact:+86-25-52320053
Address:F4-5, #17 Building, Chuang Yi Yuan, No.6 Guanghua East Street, Nanjing, 210007 P.R.China
Contact:+86-518-81061113
Address:No. 8 Lingzhou Road, Lianyungang, Jiangsu, China
Doi:10.1246/cl.1989.591
(1989)Doi:10.1021/acs.joc.7b03097
(2018)Doi:10.3390/ph13090229
(2020)Doi:10.1002/ejoc.201000170
(2010)Doi:10.1016/S0040-4039(00)99504-2
(1989)Doi:10.1055/s-1989-27234
(1989)