Triangle Pharmaceuticals is developing DAPD, a prodrug of the viral replication inhibitor dioxolane guanosine, as a potential therapy for HIV and HBV infection. Phase I/II dose range studies have commenced for HIV, and clinical development for HBV was to have commenced by late 1999 [319145], [319956]. Phase II trials are scheduled for the second quarter of 2001. The FDA has designated DAPD as a Fast Track product [365894]. DAPD is from a different nucleoside series to FTC and CS-92, which are also in development by Triangle. The compound may offer advantages over several nucleosides from other series that are already on the market because of its unique structure and pharmacological properties [247083]. Both DAPD and DXG are dioxolane purine nucleoside analogs [319660]. Preclinical data suggest DAPD may be of use in combination therapies for HIV-infected patients who are therapy-naive, in addition to patients who have previously received treatment and including those infected with drug-resistant strains of HIV-1 [341145], [341335]. Triangle licensed DAPD from Emory University [216900]. In June 1999, Triangle and Abbott Laboratories entered into an alliance for the development and marketing of six antiviral products, including DAPD [326824].

1990-12-01·Annals of the New York Academy of Sciences2区 · 综合性期刊

Antiretroviral Activity, Biochemistry, and Pharmacokinetics of 3′‐Azido‐2′,3′‐Dideoxy‐5‐Methylcytidine^a

2区 · 综合性期刊

Review

作者: B. Oswald ; R. F. Schinazi ; K. J. Doshi ; J.-P. Sommadossi ; H. M. McCLURE ; C. K. Chu ; B. F. Eriksson ; F. D. Boudinot

3'-Azido-2',3'-dideoxy-5-methylcytidine (CS-92, AzddMeC) is an antiviral nucleoside analogue structurally related to 3'-azido-3'-deoxythymidine (AZT). CS-92 is a potent and selective inhibitor of HIV-1 reverse transcriptase and HIV-1 replication in human lymphocytes and macrophages. The EC50 for CS-92 in HIV-1-infected human PBM cells was 0.09 microM. In HIV-1-infected human macrophages, the EC50 was 0.006 microM. This compound was also effective against human immunodeficiency virus type 2 in lymphocytes. The replication of Friend murine virus was only weakly inhibited, and no effect was observed against herpes simplex virus type 1 and type 2 and coxsackievirus B4. CS-92 was not toxic to PBM or Vero cells when tested up to 200 microM and was, furthermore, at least 40 times less toxic to granulocyte-macrophage and erythroid precursor cells in vitro than was AZT. The interaction of the 5'-triphosphate of CS-92 with HIV-1 reverse transcriptase indicated competitive inhibition (the inhibition constant, Kis, was 0.0093 microM) with a 30-fold greater affinity for CS-92-TP than for ddCTP. CS-92-TP inhibited HIV-1 reverse transcriptase by 50% at a concentration 6,000-fold lower than that which was required for a similar inhibition of DNA polymerase alpha. Pharmacokinetic studies showed that CS-92 was not deaminated to AZT in rats, but this compound was found to have a half-life of 2.7 hours. In rhesus monkeys, however, a compound with a retention time and ultraviolet spectra characteristics similar to AZT was detected. The mean half-life in rhesus monkeys for CS-92 was 1.52 and 1.74 h after intravenous and oral administration, respectively, and the oral bioavailability was about 21 percent. Additional preclinical studies with CS-92 will determine the ultimate utility of this antiviral agent for the treatment of HIV-1 infections.

1988-10-01·Journal of Medicinal Chemistry1区 · 医学

Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides

1区 · 医学

Article

作者: Balzarini, Jan ; Pauwels, Rudi ; De Clercq, Erik ; Janssen, Gerard ; Van Aerschot, Arthur ; Herdewijn, Piet ; Baba, Masanori

A series of base-modified pyrimidine 3'-azido-2',3'-dideoxynucleosides and 3'-substituted purine and pyrimidine 2',3'-dideoxynucleosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. The following pyrimidine derivatives emerged as the most potent and/or selective inhibitors of HIV-induced cytopathogenicity (in order of decreasing selectivity: 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AzddUrd), 3'-azido-2',3'-dideoxy-5-methylcytidine (AzddMeCyd), 3'-fluoro-ddUrd (FddUrd), 3'-fluoro-ddThd (FddThd), the N4-hydroxylated derivative of AzddMeCyd and the N4-methylated derivative of AzddMeCyd. Among the purine 2',3'-dideoxynucleosides, 3'-azido-2',3'-dideoxyguanosine (AzddGuo), 3'-fluoro-ddGuo (FddGuo), and 3'-fluoro-2,6-diaminopurine 2',3'-dideoxynucleoside (FddDAPR) were the most selective inhibitors of HIV replication.

100 项与 CS-92 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床2期	-	Georgia State University	-
HIV感染	临床2期	-	GSK Plc	-
HIV感染	临床2期	-	Gilead Sciences, Inc.	-
HIV感染	临床2期	-	Emory University	-
HIV感染	临床2期	美国	Triangle Pharmaceuticals, Inc.	-