134807-31-1Relevant articles and documents
Irreversible HIV protease inhibitors, intermediates, compositions and processes for the preparation thereof
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, (2008/06/13)
The present invention provides cis-epoxide compounds represented by formula (I-1), (I-2) or (I-3) which are useful for treating or preventing diseases caused by HIV infection: STR1 wherein: A, B, D, E, R1, R10, R11, K, G, Q, r and J have the meanings as defined in the specification.
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.