Antagonist for the Treatment of HIV

Armour, Duncan, de Groot, MarcelJ., Edwards, Martin, Perros, Manos, Price, DavidA., Stammen, BlandaL, and Wood, Anthony (2006) The discovery of CCR5 receptor antagonists for the treatment of HIV infection Hit-to-Lead studies. ChemMedChem, 1 (7), 706-709. 

Pryde, D.C. (2007) CCR5 Antagonists for the Treatment of HIV. 16th Camerino-Noordwijkerhout Symposium, An Overview of Receptor Chemistry. 2007 Camerino, Italy. 

Palani, A. et al. (2001) Discovery of 4-[(Z)-(4-Bromophenyl)(ethoxyimino) methyl]-l -[(2,4-dimethyl-3-pyridinyl) carbonyl]-4 -methyl-l,4 -bipiperidine N-Oxide (SCH 351125) An orally bioavailable human CCR5 antagonist for the treatment of HIV infection. Journal of Medicinal Chemistry, 44 (21), 3339-3342. 

Kazmierski, W.M. et al. (2004) Preparation of benzimidazolylaza-bicyclooctylethylpiperidines as CcrS antagonists for the treatment of HIV infection. Application WO 2004054974. 

Perros, M, (2007) CCR5 antagonists for the treatment of HIV infection and aids. Advances in Antiviral Drug Design, 5, 185-212. 

Lieberman-Blum, S.S., Fung, H.B., and Bandres, J.C. (2008) Maraviroc a CCR5-receptor antagonist for the treatment of HIV-1 infection. Clinical Therapeutics, 30, 1228-1250. 

Treatment of HIV infection using chemokine-receptor antagonists has been the most intensively studied of all potential therapeutic uses of this nature. Use of chemokine-receptor antagonists for the treatment of HIV is much simpler than for the treatment of inflammatory disease or malignancy, because essentially only two receptors are involved, CCR5 and CXCR4. 

Wood A, Armour D (2005) The discovery of the CCR5 receptor antagonist, UK-427,857, a new agent for the treatment of HIV infection and AIDS, Prog Med Chem 43 239-271... 

CCR5 expression likely plays a role in T-cell recruitment and may be involved in the development of autoimmune diseases. There is a negative association between the CCR5A32 mutation and rheumatoid arthritis (Prahalad 2006). Furthermore, additional studies reviewed elsewhere suggest the involvement of CCR5 in multiple sclerosis, diabetes, and transplant rejection (Ribeiro and Horuk 2005). As such, it is likely that CCR5 antagonists developed for the treatment of HIV-1 infection can also be used for other diseases. 

Chemokine CCR5 receptor antagonists vicriviroc and mamviroc prevent viral entry into white blood cells. They are, respectively, undergoing Phase II and Phase III clinical trials for the treatment of HIV infection as part of polytherapies. ... 

Maraviroc was granted regulatory approval in the United States and Europe in 2007 as the first prescribed CCR5 antagonist for the treatment of CCR5-tropic confirmed HIV-1 infection in treatment-experienced patients. Maraviroc is sold under the tradename Selzentry (Celsentri in Europe and Canada) [61]. 

Kim, D. et al. (2001) Design, synthesis, and SAR of heteroqfde-containing antagonists of the human CCR5 receptor for the treatment of HIV-1 infection. Bioorgank S. Medicinal Chemistry Letters, 11 (24), 3103-3106. 

Maraviroc is a cell surface chemokine receptor CCR5 antagonist, approved for the treatment of HIV-1 infection in treatment-experienced patients with CCR5 tropic HIV-1. It is used in combination with other antiretroviral drugs. It has no activity against CXCR4 tropic virus [238 ]. Inhibition of CCR5 blocks the entry of HIV-1 into the cell. 

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. 

The benzodiazepines (177) and (178) are HIV-Tat antagonists and are being evaluated as therapies for the treatment of AIDS <9iscii,799> as is the HIV-1 reverse transcriptase inhibitor nevirapine (179) <90SCI1411>. The natural product azepinomycin (180) is reported to be an antibiotic with antitumour properties <88H(27)ii63> and anthramycin (181) is an antineoplastic agent. 

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