134805-77-9Relevant academic research and scientific papers
Design, synthesis, evaluation, and crystallographic-based structural studies of HIV-1 protease inhibitors with reduced response to the V82A mutation
Clemente, José C.,Robbins, Arthur,Gra?a, Paula,Paleo, M. Rita,Correa, Juan F.,Villaverde, M. Carmen,Sardina, F. Javier,Govindasamy, Lakshmanan,Agbandje-McKenna, Mavis,McKenna, Robert,Dunn, Ben M.,Sussman, Fredy
, p. 852 - 860 (2008/09/20)
In our quest for HIV-1 protease inhibitors that are not affected by the V82A resistance mutation, we have synthesized and tested a second generation set of C2-symmetric HIV-1 protease inhibitors that contain a cyclohexane group at P1 and/or P1′
Symmetry-Based Inhibitors of HIV Protease. Structure-Activity Studies of Acylated 2,4-Diamino-1,5-diphenyl-3-hydroxypentane and 2,5-Diamino-1,6-diphenylhexane-3,4-diol
Kempf, Dale J.,Codacovi, Lynnmarie,Wang, Xiu Chun,Kohlbrenner, William E.,Wideburg, Norman E.,et al.
, p. 320 - 330 (2007/10/02)
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.
