Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection.
نویسندگان
چکیده
Human immunodeficiency virus type-1 (HIV-1) integrase is one of the three virally encoded enzymes required for replication and therefore a rational target for chemotherapeutic intervention in the treatment of HIV-1 infection. We report here the discovery of Raltegravir, the first HIV-integrase inhibitor approved by FDA for the treatment of HIV infection. It derives from the evolution of 5,6-dihydroxypyrimidine-4-carboxamides and N-methyl-4-hydroxypyrimidinone-carboxamides, which exhibited potent inhibition of the HIV-integrase catalyzed strand transfer process. Structural modifications on these molecules were made in order to maximize potency as HIV-integrase inhibitors against the wild type virus, a selection of mutants, and optimize the selectivity, pharmacokinetic, and metabolic profiles in preclinical species. The good profile of Raltegravir has enabled its progression toward the end of phase III clinical trials for the treatment of HIV-1 infection and culminated with the FDA approval as the first HIV-integrase inhibitor for the treatment of HIV-1 infection.
منابع مشابه
Raltegravir: Its use in the Treatment of HIV Infection
Raltegravir is the fi rst integrase strand transfer inhibitor to be approved for the treatment of HIV infection. Administered orally in doses of 400 mg twice daily, it is well-tolerated and has minimal drug-drug interactions with coadministered antiretrovirals and other agents. In clinical trials including treatment-experienced and treatment-naïve HIV-infected adults, raltegravir in combination...
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The development of multiple agents with potent antiretroviral activity against HIV has ushered in a new age of optimism in the management of patients infected with the virus. However, the viruses' dynamic ability to develop resistance against these agents necessitates the investigation of novel targets for viral suppression. Raltegravir represents a first-in-class agent targeting the HIV integr...
متن کاملRaltegravir: first in class HIV integrase inhibitor
On October 16, 2007, the US Food and Drug Administration (FDA) approved raltegravir for treatment of human immunodeficiency virus (HIV)-1 infection in combination with other antiretroviral agents in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Raltegravir is first in a novel class of antiretroviral dru...
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Raltegravir is the first approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor; it targets the strand transfer step of HIV-1 integration. Clinical trials have demonstrated that raltegravir-containing regimens have potent antiretroviral activity and are well tolerated in HIV-1-infected individuals. In antiretroviral treatment-experienced persons with drug-resistant HIV infecti...
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Raltegravir is a first-in-class HIV-1 integrase inhibitor with established antiviral efficacy in treatment-naive and treatment-experienced patients with multidrug-resistant HIV-1 infection. In this article, we summarize pharmacoeconomic evaluations of raltegravir-based treatment regimens, compared with alternative therapies, in the treatment of patients with HIV infection and/or AIDS. Cost-effe...
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ورودعنوان ژورنال:
- Journal of medicinal chemistry
دوره 51 18 شماره
صفحات -
تاریخ انتشار 2008