Human immunodeficiency virus preparations

Bryant, D. K., R. C. Orlando, C. Fenselau, R. C. Sowder, L. E. Henderson, Four-sector tandem MS analysis of complex mixtures of phosphatidylcholines present in a human immunodeficiency virus preparation. Anal. Chem., 1991,63, 1110-1114. 

It overcomes problems of product safety. Direct extraction of product from some native biological sources has, in the past, led to the unwitting transmission of disease. Examples include the transmission of blood-borne pathogens such as hepatitis B and C and human immunodeficiency virus (HIV) via infected blood products and the transmission of Creutzfeldt-Jakob disease to persons receiving human growth hormone (GH) preparations derived from human pituitaries. 

Dideoxyuridine (ddU) is an antiviral agent that proved ineffective at controlling human immunodeficiency virus type 1 (HIV-1) infection in human T-cells. This ineffectiveness was ascribed to a lack of substrate affinity of ddU for cellular nucleoside kinases, which prevent it from being metabolized to the active 5 -triphosphate. To overcome this problem, bis[(pivaloyloxy)methyl] 2, 3 -dideoxyuridine 5 -monophosphate (9.41) was prepared and shown to be a membrane-permeable prodrug of 2, 3 -di-deoxyuridine 5 -monophosphate (ddUMP, 9.42) [93]. Indeed, human T-cell lines exposed to 9.41 rapidly formed the mono-, di-, and triphosphate of ddU, and antiviral activity was observed. This example again documents... 

Pyrrolopyridines substituted at the 2-position of dipyridodiazepinones have been prepared for study as nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase <1997JME2430>. Compound 141, synthesized from pyrrolo[2,3-, ]pyridine as a starting material, has emerged as a novel inhibitor of HIV-1. Compound 141 acts by interfering with the initial viral entry process <2003JME4236>. 

Furoannelated analogs of uracil acyclic nucleosides were prepared as compounds with potential as anti-HIV agents (HIV = human immunodeficiency virus). Hence, 6-benzyluracil 320 is converted to the precursor 321 first by hydroxymethylation, silylation in situ with bis(trimethylsilyl)acetamide (BSA), then by alkylation (Scheme 28) <2001S559>. Ring closure to 322 was effected by treatment with lead tetraacetate and calcium carbonate <2004AP148>. 

The history of combating the human immunodeficiency virus (HIV) can be viewed as a model of today s development of pharmaceuticals (Stone, 1995). Since the middle of the 1980s a total of 20 anti-AIDS pharmaceuticals based on 16 distinct chemical entities have been introduced into the market the first was AZT by Glaxo in 1987. A causal therapy, however, has not been developed yet. Most advantageous effects of today s actives are temporary because HIV is characterized by an extreme mutability and can cause resistance phenomena through rapid mutation within months or sometimes weeks against most approved preparations or those in clinical phases. The criterion for efficacy is the reduction of the number, or even total elimination, of viruses in the blood combined with an enhanced count of C D4-T-lymphocytes. 

A microbial reduction with a Rhodococcus erythropolis strain was used by BMS scientists to prepare the chiral chlorohydrin from the chloroketone (Scheme 19.15). This intermediate is incorporated into the human immunodeficiency virus (HIV) protease inhibitor Atazanavir (26). This strain was identified through screening and provided >90% yield with a diastereomeric purity of >98% and an ee of >99%.62... 

The transmission of viral infections by immunoglobulins has occasionally been suspected. However, intravenous immunoglobulin preparations are considered relatively safe, and there are no reports of transmission of HIV or hepatitis B (44,101). This is probably because of the high degree of viral inactivation of the cold ethanol fractionation and the screening of every donation for several viruses, such as HIV and hepatitis B and C (85). Of 56 patients with autoimmune diseases who received 167 infusions of intravenous immunoglobulin, none developed antibodies to human immunodeficiency virus and hepatitis C virus or hepatitis B surface antigen (12). 

The natural product (-)-oxetanocin is an unprecedented oxetanosyl-A/-glycoside that inhibits the in vitro replication of human immunodeficiency virus (HIV). In order to prepare multigram quantities of the compound, D.W. Norbeck et al. devised a short and efficient synthetic strategy. The cornerstone of the strategy was the Wolff rearrangement of a five-membered diazo ketone. The diazo transfer was achieved by first converting the ketone to an enamino ketone followed by treatment with triflyl azide. Upon irradiation with a 450 W Pyrex filtered Hanovia lamp, the isomeric oxetanes (a 3 = 2 1) were obtained in 36% yield. 

Lyophilized and liquid preparations containing various enzymes are available from commercial sources, and these have a usefid function in quality control. Serum pools can also be prepared in the laboratory for quality control purposes (with care to exclude any specimens contaminated with hepatitis virus or human immunodeficiency virus), then assayed for enzyme activity and stored m a freezer in small portions for daily use. 

Holodniy M, Rainen L, Herman S, Yen-Lieberman B, Stability of plasma human immunodeficiency virus load in VACUTAINER PPT plasma preparation tubes during overnight shipment, J Clin Microbiol 2000 38 323-6. 

The appetite-stimulating effects of marijuana have been known for centuries and constitute one of the established medicinal uses of cannabis preparations. Today THC (dronabinol/Marinol) is clinically used for the treatment of cachexia-anorexia in human immunodeficiency virus (HIV) and palliative care patients. There have also been very promising advances in the development of a cannabinoid receptor antagonist (SR141716A, now named Rimonabant or Acomplia) for the treatment of obesity. 

Abrams et al. (2003) reported the effects of smoked cannabis in painful peripheral neuropathy secondary to human immunodeficiency virus (HIV) and/or antiretroviral treatment. In a preliminary uncontrolled pilot study (in preparation for a planned placebo-controlled trial) excellent correlation was reported between cannabis dosing and pain improvement, with 10 of 16 participants experiencing a greater than 30% reduction in pain. These results provide the ethical justification to proceed with the controlled trial. 

Three categories of agents against the human immunodeficiency virus (HIV) are nucleoside analogues, protease inhibitors, such as thiourea derivatives. Therefore, Le and his coworkers developed a simple, mild, and efficient method for the synthesis of thiourea derivatives via the reaction of phenyl isothiocyanate and amines in [bmim][BF ] (Fig. 12.2) [2]. The method is also useful for the preparation of... 

Most hypotheses relating infection to autoimmunity have assumed that infection has a direct causal role. However, an alternative is that infection prepares the ground for the seed that is the actual cause of disease. Infections are known to be critical to current immune responsiveness. Human immunodeficiency virus (HIV) is an obvious example, but measles virus, Epstein-Barr virus,... 

Wang T. Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) attachment. Part x. SAR of 4-Methoxy 6-Azaindole series of HIV gpl20 entry inhibitors and discovery of BMS-626529 and its phosphonoxymethyl prodrug BMS-663068 (Manuscript in preparation)... 

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