HIV-1 inhibitor

Li F, GoUa-Gaur R, Salzwedel K, Kilgore NR, Reddick M, MataUana C, Castillo A, Zoumplis D, Martin DE, Orenstein JM et al. (2003) PA-457 a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc Natl Acad SciUSA 100 13555-13560... 

The identification of the HIV-1-specific non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a separate class of HIV inhibitors was heralded by the discovery of the tetrahydroimidazo[4,5,1 -// .][ 1,4]benzo-diazepin-2(l //)-onc and -thione (TIBO) derivatives (Fig. 7) [58,59] and 1 -(2-hydroxyethoxymethyl)-6-(phenylthio)thymine (HEPT) derivatives (Fig. 8) [60,61]. The first TIBO derivatives (R82150, R82913) were the first NNRTIs [58] postulated to act as inhibitors of HIV-1 RT [59], For the HEPT derivatives it became evident that they also interact specifically with HIV-1 RT after a number of derivatives (i.e., E-EPU, E-EBU, and E-EBU-dM) had been synthesized that were more active than HEPT itself [62,63]. Following HEPT and TIBO, several other compounds, i.e., nevirapine, pyridinone, and bis(heteroaryl)piperazine (BHAP), were... 

De Clercq E. HIV inhibitors targeted at the reverse transcriptase. AIDS Res Human Retrovir 1992 8 119-134. 

Two approaches that have been validated for HIV inhibitors, nucleoside 5 -phosphonates [48] and 1,3-dioxolane analogs [49] have proven unsuccessful when applied to HCV inhibitors. Phosphonodiphosphates have been synthesized and are incorporated by NS5B RdRp, but Vmax/Km for these chain terminators is 10-100-fold less than for ATP, and potency must be greatly improved for analogs of this type to have utility [50]. A small series of 1,3-dioxolanes also failed to afford active inhibitors of HCV, or HIV, despite the addition of a 5-methyl substituent to impose the desired conformational preference [51]. Ring expanded nucleobases [52,53] and AICAR analogs have also been synthesized as HCV inhibitors which provide only weak replicon activity [54]. 

The oxidative carbonylation of amines to give ureas is at present one of the most attractive ways for synthesizing this very important class of carbonyl compounds via a phosgene-free approach. Ureas find extensive application as agrochemicals, dyes, antioxidants, resin precursors, synthetic intermediates (also for the production of carbamates and isocyanates), and HIV-inhibitors. Many transition metals (incuding Au [244], Co [248,253-255], Cu [242], Mn [249,256-258], Ni [259], Rh [246,247,260-262], Ru [224,260,263] and especially Pd [219,225,226,264-276], and, more recently, W [277-283]) as well as main-group elements (such as sulfur [284-286] and selenium [287— 292]) have been reported to promote the oxidative carbonylation of amines, usually under catalytic conditions. In some cases, carbamates and/or oxamides are formed as byproducts, thus lowering the selectivity of the process. 

Castanospermine is a plant alkaloid isolated from the seeds of the Australian chestnut tree, Castanospermium australe. As with most anti-HIV inhibitors, the discovery of the compound predates the time of isolation of HIV-1. The compound inhibits a-glucosidase-1, and therefore normal processing of the glycopro-... 

Johnson, M. D., Hoesterey, B. L., and Anderson, B. D. 1994. Solubilization of a tripeptide HIV inhibitor using a combination of ionization and complexation with chemically modi ed cyclodexJrififciarm. Sci. 

In addition to the above examples, there are still a large number of bioactive natural products and various synthetic and semisynthetic enol-containing compounds that serve as potential and promising drugs for various therapeutic purposes such as the non-peptidyl HIV inhibitor Aptivus (tipranavir Section IV.1) and the third-generation tetracycline antibiotics (Section IV.H). The structure and function of the metal complexes of some... 

In the continuous quest for new generations of HIV inhibitors, Pfizer identified the thiosubstituted pyrones as a new class of non-peptidic protease inhibitors [97]. 

Fullerenes and their derivatives are of broad interest in various fields ranging from ferromagnetism [87] over their application as possible HIV inhibitors [88] to tumor-therapeutic active substance in biological systems [89]. Although C6o is insoluble in water, dissolution may be accomplished by using water-soluble polymers [90] or surfactant solutions containing amphiphilic block-copolymers [91], micelles or liposomes [92, 93]. The immobilization of... 

Indications Anticancer (stomach, colorectal, lung, prostate), arthritis, asthma, heart disease, HIV inhibitor. Treatment of dandruff, fungal infections (tinea versicolor), and seborrhea Category Antioxidant Trace element... 

HIV inhibitor treatment eventually leads to the selection of resistant mutations, one key reason being that the reverse transcriptase is error prone since it lacks the 3 exonuclease activity. Currently, combinatorial inhibitors with different protein targets, for example, two reverse transcriptase (RT) nucleoside inhibitors and one protease inhibitor (PI), are used in highly active antiretroviral... 

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