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Anti-HIV-1 agent

Recent advances in the discovery and development of plant-derived natural products and their analogs, in particular polycyclic 0-heterocycles, as anti-HIV agents 99PACI045. [Pg.233]

F. 3 Structural formulae of 2, 3 -dideoxynucleoside analogues (anti-HIV) agents... [Pg.62]

There are currently six major antiretroviral drug families (Table 5). Nucleoside reverse transcriptase inhibitors (NRTI) are nucleoside analogs (discussed in more detail in chapter by De Clercq and Neyts, this volume) and were the first approved antiretroviral agents. They include drugs such as AZT, didanosine (ddl), stavudine (d4T), abacavir (ABC), and lamivudine (3TC), the latest used at doses of 300 mg daily as anti-HIV agent (lOOmg/day is the dosing approved for treatment of HBV... [Pg.334]

Using water as the solvent enhanced the rate of the hetero-Diels-Alder reaction relative to the dimerization of cyclopentadiene. In addition, the reaction is much faster at a low pH, which implies that the reaction is acid catalyzed. The 5,5-fused system generated has been used in the total synthesis of several bioactive compounds, including the anti-HIV agent (—)-carbovir (Eq. 12.51)121 and the hydroxylactone moiety of mevinic acids (Eq. 12.52).122... [Pg.404]

In addition to the three anti-HIV agents [AZT (zidovudine), DDI (dida-nosine) and DDC (zalcitabine)] that have been formally approved by the U.S. Food and Drug Administration for the treatment of HIV infections, several other 2, 3 -dideoxynucleoside (ddN) analogues (Fig. 5), including 3 -fluoro-2, 3 -didcoxy-5-chlorouridine (FddClUrd) and 2, 3 -didehydro-... [Pg.319]

De Clercq E. Anti-HIV agents interfering with the initial stages of the HIV replicative cycle. In Morrow WJW, Haigwood NL, eds. HIV Molecular Organization, Pathogenicity and Treatment. Amsterdam Elsevier Science Publishers, 1993 267-292. [Pg.330]

Miyasaka T, Tanaka H, Baba M, Hayakawa H, Walker RT, Balzarini J, De Clercq E. A novel lead for specific anti-HIV agents l-(2-hydroxyethoxy)-methyl]-6-(phcnylthio)thyminc. J Med Chem 1989 32 2507 -2509. [Pg.335]

Arylmethyl-9-hydroxypyrazino[l,2-f]pyrimidine-l,8-dione derivatives have been claimed as anti-HIV agents <2005W02005/016927, 2005W02005/087766> 6,8-dioxo-pyrazino[l,2-f]pyrimidine-3-carboxamides 164 (Y = NH) <2004W02004/014354> and their saturated analogues <2004USP2004/034009> have been claimed as matrix metalloproteinase MMP-13 enzyme inhibitors, useful in the treatment of rheumatoid arthritis. [Pg.293]

Pal, D., C. Udata, and A. K. Mitra. Transport of cosalane-a highly lipophilic novel anti-HIV agent-across caco-2 cell monolayers, J. Pharm. Sci. [Pg.85]

To determine if the high in vitro potents of the anti-HIV compound 30 translates into antiviral efficiency in vivo, Datema et al. investigated the inhibition of HIV-1 production and of depletion of human T cells in HIV-1-infected SCID-hu Thy/Liv mice [37]. Steady levels of 100 ng of 30 or higher per mL in plasma resulted in significant inhibition of HIV p24 protein formation. Daily injection of 30 caused a dose-dependent decrease in viral p24 production, and this inhibition could be potentiated by coadministration of AZT (or DDI). This study suggested that 30 alone or in combination with the licensed anti-HIV agents AZT and DDI may decrease the virus load in HIV-infected patients and, by extension, that the infectious cell entry step is a valid target for antiviral chemotherapy of HIV disease. [Pg.161]

The discovery of in vitro anti-HIV activity of macrocyclic polyamines by the Kimura and De Clercq groups led to development of a new type of effective anti-HIV agents. The results from the studies of the pharmacokinetics and their in vivo efficacy in a SCID-hu Thy/Liv mice are further encouraging indicators of their potential usefulness as new AIDS curing drugs. [Pg.162]

MACROCYCLIC POLYAMINES AND THEIR METAL COMPLEXES A NOVEL TYPE OF ANTI-HIV AGENT... [Pg.258]

Rationale for CCR5-based entry inhibitors as anti-HIV agents... [Pg.302]

There is a need for more effective anti-HIV agents, especially since resistance to all the currently used agents is beginning to develop a combination of different agents targeting different stages of the virus replicative cycle could provide a more effective therapy (348). [Pg.244]

Ribozymes are a class of metallo-enzymes based on RNA rather than proteins. They have potential in clinical medicine, for example, as potential anti-HIV agents (568, 569) and as possible new tools for the treatment of cancer (570). The active structures of ribozymes contain domains of stacked helices which pack together through tertiary contacts. Divalent metal ions such as Mg(II), Zn(II), and Mn(II) can tune the reactivity and shape the structures of ribozymes (571). Manganese(II) and Mg(II) have similar hexacoordinate ionic radii (0.86 and 0.97 A, respectively) (572) and octahedral geometry ( )Ka of hydrates Ca(II), 12.7 Mg(II), 11.4 Mn(II), 10.7 Zn2+, 9.6) (571). There are several potential oxygen donors on the ribose sugar moiety. [Pg.276]

Many antiviral agents, particularly some anti-HIV agents, have rather short plasma half-lives, which require frequent oral administration of the agent. Thirteen-week studies have been conducted with t.i.d. dosing of rats and monkeys, requiring around-the-clock shift work for technical staff of the laboratory. [Pg.243]

Boron is an essential trace element for plants, and may well turn out to be essential for mammals as well. The boron-containing polyether-macrolide antibiotic, boromycin, was isolated as a potent anti-HIV agent. [Pg.3]

Ueno, R. and Kuno, S. Dextran sulfate, a potent anti-HIV agent in vitro having synergism with zidovudine. Lancet, 1987, 1379. [Pg.233]

Cragg GM, Schepartz SA, Sufftiess M, Grever MR. (1993) The taxol supply crisis. New NCI policies for handling the largescale production of novel natural product anticancer and anti-HIV agents. J Nat Prod 56 1657-1668. [Pg.118]

Kashiwada Y, Hashimoto E, Cosentino LM, Chen C-H, Garrett PE, Lee K-H. (1996) Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents. J Med Chem 39 1016-1017. [Pg.161]

The development of antiretroviral therapy has been a major challenge since the discovery of the human inununodeficiency virus (HIV). Early successes with nucleoside and non-nucleoside reverse transcriptase (RT) inhibitors, as well as the development of protease inhibitors have facilitated, in recent years, a highly active antiretroviral therapy (HAART), where a combination of drugs is simultaneously administered. In spite of significant improvements in the morbidity and mortality of HIV-infected patients, the rapid appearance of resistant HIV-variants, as well as adverse effects and high cost of contemporary drugs necessitate the continuous development of independent classes of anti-HIV agents. ... [Pg.268]


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