European Journal of Medicinal Chemistry p. 199 - 211 (2017)
Update date:2022-07-30
Topics:
Zou, Yi
Wang, Yan
Wang, Fang
Luo, Minghao
Li, Yuezhen
Liu, Wen
Huang, Zhangjian
Zhang, Yihua
Guo, Wenjie
Xu, Qiang
Lai, Yisheng
Indoleamine 2,3-dioxygenase 1 (IDO1) is frequently hijacked by tumors to escape the host immune response, and the enzyme is now firmly established as an attractive target for cancer immunotherapy. To identify novel IDO1 inhibitors suitable for drug development, a scaffold-hopping strategy combined with the average electrostatic potentials calculation was ultilized to design novel benzoxazolinone derivatives. Among these, compounds 7e, 7f and 9c exhibited the inhibitory potency in the low micromolar range and displayed negligible level of cytotoxicity against HeLa cells. Treatment with these three compounds promoted the proliferation of T lymphocyte and led to the dramatic decrease of regulatory T cells in the B16F1 cells and na?ve T cells co-culture system. Subsequent spectroscopic experiments suggested that these benzoxazolinones formed a coordinate bond with the heme iron to stabilize the complex. This study suggested that the benzoxazolinone was an interesting scaffold for discovering novel IDO1 inhibitors, and these compounds are attractive candidates for further development.
View MoreHangzhou Share Chemical Co., Ltd
Contact:+86-57187093700
Address:Hang Xing Road
Tangshan Wisdom Trading Co.,Ltd
Contact:86 315 2222979
Address:No.41 BeiXinXi Road, Yangguang building 1-1102 , Tangshan, Hebei, China
ANHUI CHEM-BRIGHT BIOENGINEERING CO.,LTD
Contact:86-561-4080321
Address:No.8 Lieshan Industrial Zone of Huaibei
KA-SHING Business Trade Macau Co., Ltd.
Contact:00853-28430045
Address:23rd Floor, Block 3 La Cite, Areia Preta, Macao
Linyi Shengxin Pharmaceutical R&D Co., Ltd
Contact:+86-18653953873
Address:West First of Yufeng Road, Yishui County
Doi:10.1021/ja00197a049
(1989)Doi:10.1016/S0960-894X(01)00545-5
(2001)Doi:10.1021/ja00197a073
(1989)Doi:10.1016/j.tetlet.2009.12.128
(2010)Doi:10.1021/ol902973r
(2010)Doi:10.1039/c3ra46414h
(2014)