Journal of Medicinal Chemistry p. 7252 - 7267 (2016)
Update date:2022-08-03
Topics:
De Turiso, Felix Gonzalez-Lopez
Hao, Xiaolin
Shin, Youngsook
Bui, Minna
Campuzano, Iain D. G.
Cardozo, Mario
Dunn, Michelle C.
Duquette, Jason
Fisher, Benjamin
Foti, Robert S.
Henne, Kirk
He, Xiao
Hu, Yi-Ling
Kelly, Ron C.
Johnson, Michael G.
Lucas, Brian S.
McCarter, John
McGee, Lawrence R.
Medina, Julio C.
Metz, Daniela
San Miguel, Tisha
Mohn, Deanna
Tran, Thuy
Vissinga, Christine
Wannberg, Sharon
Whittington, Douglas A.
Whoriskey, John
Yu, Gang
Zalameda, Leeanne
Zhang, Xuxia
Cushing, Timothy D.
Optimization of the potency and pharmacokinetic profile of 2,3,4-trisubstituted quinoline, 4, led to the discovery of two potent, selective, and orally bioavailable PI3Kδ inhibitors, 6a (AM-0687) and 7 (AM-1430). On the basis of their improved profile, these analogs were selected for in vivo pharmacodynamic (PD) and efficacy experiments in animal models of inflammation. The in vivo PD studies, which were carried out in a mouse pAKT inhibition animal model, confirmed the observed potency of 6a and 7 in biochemical and cellular assays. Efficacy experiments in a keyhole limpet hemocyanin model in rats demonstrated that administration of either 6a or 7 resulted in a strong dose-dependent reduction of IgG and IgM specific antibodies. The excellent in vitro and in vivo profiles of these analogs make them suitable for further development.
View MoreWuhan Silworld Chemical Co.,Ltd
website:http://www.silworldchemical.com
Contact:+86-27-85613400
Address:No.198 jiangjun Road, Wuhan,China 430033
Shijiazhuang Haotian Chemical Co., Ltd.
Contact:86-311-85044374
Address:293 Donggang Road
jintan yufan Medicine Raw materials Co.,Ltd.(expird)
Contact:86-519-82808282
Address:6th,Jincheng Huangzhuang
NINGXIA DARONG CHEMICALS & METALLURGY CO.,LTD.
Contact:86-952-2179751
Address:Darong Road, Dawukou, Shizuishan, Ningxia 753001, China
Guangxi Nanning Guangtai Agriculture Chemical Co.,Ltd
Contact:+86-771-2311266
Address:Room703,Building12, Software Park Phase II,NO.68,Keyuan Road,Nanning City,Guangxi,China
Doi:10.1021/ol102652t
(2011)Doi:10.1021/ja00163a027
(1990)Doi:10.1055/s-0030-1261235
(2011)Doi:10.1021/ja01023a071
(1968)Doi:10.1007/BF00486767
()Doi:10.1039/a809005j
(1999)