1051375-16-6

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Questions And Answer

• Synthesis

  Under nitrogen protection, lithium bromide (10.60 g, 122.06 mmol) was added to a solution of GSK1349572 precursor compound amide (23.0 g) in acetonitrile (460 mL, 20 volumes). The resulting reaction mixture was heated to 85 °C and reacted at 85 °C for 3 hours. The reaction progress was monitored by TLC. After the reaction was complete, the reaction system was cooled to room temperature. Then, 0.5 N hydrochloric acid (460 mL) was added to the reaction mixture, and the resulting mixture was stirred at 20–25 °C for 3 hours. The solids in the reaction mixture were then filtered, and the solids were washed for 30 minutes with a mixture of acetonitrile and water (1:1, 100 mL).

  The wet solid was dissolved in acetonitrile (230 mL). 230 mL of water was slowly added to the reaction mixture at 20-25°C. The mixture was stirred for 2 hours, filtered, and the filter cake was washed with acetonitrile. The resulting solid was dried under vacuum at 40-45°C for 6 hours to obtain the target product molecule.;

• Anti-AIDS drugs

  Dolutegravir (Tivicay) was a new kind of anti-ADIS drug that jointly developed by the British pharmaceutical giant GlaxoSmithKline (GSK) with the Japanese Shionogi Pharmaceutical Company (Shionogi).
  In July 2012, the GlaxoSmithKline Pharmaceuticals and Japan's Shionogi Pharmaceutical Company announced the results of Phase III clinical trial of the new AIDS drug Dolutegravir. After 48 weeks of treatment with dolutegravir and two other older versions of the AIDS drug, 88% of the virus in vivo was successfully inhibited, while the use of Gilead Sciences (Gilead Sciences) of the three-in-one oral drug Atripla (Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate), 81% of the virus in patients was inhibited, which can be seen that, the dolutegravir developed by the GlaxoSmithKline pharmaceutical companies is slightly better. According to the researchers, in a comparative trial, owing to the side effects of the drugs, 10% of the patients stopped taking the Atripla drug developed from Gilead Technologies while only 2% stopped taking GlaxoSmithKline's dolutegravir Drug, therefore, we can see that the dolutegravir drugs from GlaxoSmithKline has slightly higher safety.
  On August 12, 2013, the US Food and Drug Administration (FDA) approved the use of dolutegravir for being used in previously treated or early treated HIV-1 adults and 12 years of age and above infected children of at least 40 kg.
  Dolutegravir is a once-daily drug with its efficacy being comparable to Merck's HIV/AIDS drug Raltegravir (Isentress) in Phase III clinical trials. Raltegravir should be subject to daily administration twice. Both of them are inhibitors of HIV integrase. The FDA official claim that the AIDS patient should be subject to targeted treatment on a case-by-case basis. Tivicay will provide patients with new options. In a study done a year ago, 88% of patients had a significant improvement after 48 weeks of Tivicay treatment, better than the efficacy of the Gilead's Atripla. Analysts expect that Dolutegravir will become a multi-billion-dollar blockbuster drug and a strong contender for Atripla, the world's best-selling HIV drug, developed by Gilead Sciences.
  Common name: Dolutegravir
  Trade name: Tivicay
  Alias: GSK1349572, S-349572, GSK572
  Drug Company: GlaxoSmithKline
  Indications: AIDS
  Drug type: integrase inhibitors
  Approved date: August 12, 2013 (US)
  CAS Registry Number: 1051375-16-6
  Chemical name: (4R, 12aS)-N-[(2, 4-difluorophenyl) methyl]-3, 4, 6, 8, 12, 12a-hexahydro-7-hydroxy-Dioxo-2H-pyrido [1 ', 2': 4,5] pyrazino [2,1-b] [1,3] oxazine-9-carboxamide
  U.S. Patent No. 8,129,385
  The patent expires on October 5, 2027
  International patent: W02006116764
  This information is compiled and edited by Xiao Nan of Chemicalbook.;

• Uses

  Dolutegravir (GSK1349572) is a HIV integrase inhibitor with an IC50 of 2.7 nM and is moderately effective against the significant mutants Y143R, Q148K, N155H, and G140S/Q148H against Raltegravir.;

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