Journal of Medicinal Chemistry p. 320 - 330 (1993)
Update date:2022-09-26
Topics:
Kempf, Dale J.
Codacovi, Lynnmarie
Wang, Xiu Chun
Kohlbrenner, William E.
Wideburg, Norman E.
et al.
The structure-activity relationships in two series of novel, symmetry-based inhibitors of HIV protease, the enzyme responsible for maturation of the human immunodeficiency virus, are described.Beginning with lead compounds 3-6, the effect of adding polar, heterocyclic end groups to one or both ends of the symmetric or pseudosymmetric inhibitors was probed.Aqueous solubility was enhanced >1000-fold while maintaining potent inhibition of purified HIV-1 protease and anti-HIV activity in vitro.Pharmacokinetic studies in rats indicated a substantial difference in the absorption properties of mono-ol-based and diol-based inhibitors.The oral bioavailability of inhibitor 19 in rats was 19percent; however, the Cmax obtained failed to exceed the anti-HIV EC50 in vitro.Substantial plasma levels of potent inhibitors of the diol class were not obtained after oral administration in rats; however, the optimal combination of aqueous solubility and in vitro antiviral activity of several inhibitors support their potential use in intravenous therapy.
View MoreZhejiang Kente Chemical Co.,Ltd.
Contact:86-0576-87651912
Address:No.7, Fengxi West Road, Modern Industrial Zone
Shandong Bolode Bio-Technology Co., LTD
Contact:+86-0531-58966870
Address:136 Jingyi Road,Huaiyin District,Jinan,Shandong,China
Tangshan Moneide Trading Co., Ltd.
Contact:+86-315-8309571
Address:2-7-420 Jidong Building Materials Commercial Center, Tangshan, Hebei, 064000 China
Contact:86-571-86737118-8689
Address:No.69, 12 Street, HEDA, Hangzhou, Zhejiang, China
Shandong Topscience Biotech Co., Ltd.
Contact:0633-2619278
Address:No. 98 Lanshan West Road, Lanshan District, Rizhao, Shandong Province, P.R. of China
Doi:10.1016/0223-5234(96)88246-8
(1995)Doi:10.1021/ml300262e
(2013)Doi:10.1021/jo00307a027
(1990)Doi:10.1021/jm301597s
(2012)Doi:10.1080/00397911.2011.602498
(2013)Doi:10.1016/j.ejmech.2012.09.031
(2012)