Showing posts with label US 20150011782. Show all posts
Showing posts with label US 20150011782. Show all posts

Tuesday, 3 March 2015

US 20150011782 New patent .....Amprenavir

Amprenavir skeletal.svg
KVX-478, 141W94, VX-478,
(3S)-Tetrahydro-3-furanyl ((1S,2R)-3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)carbamate
(3S)-tetrahydro-3-furyl N-[(1S,2R)-3-(4-amino-N-isobutylbenzenesulphonamido)-1-benzyl-2-hydroxypropyl] carbamate
CAS NO. 161814-49-9, [(3S)-oxolan-3-yl] N-[(2S,3R)-4-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
Weight 505.224656557
Chemical Formula C25H35N3O6S

Amprenavir is a protease inhibitor used to treat HIV infection.
Amprenavir (Agenerase, GlaxoSmithKline) is a protease inhibitor used to treat HIV infection. It was approved by the Food and Drug Administration on April 15, 1999, for twice-a-day dosing instead of needing to be taken every eight hours. The convenient dosing came at a price, as the dose required is 1,200 mg, delivered in eight very large gel capsules.
Production of amprenavir was discontinued by the manufacturer December 31, 2004; a prodrug version (fosamprenavir) is available.

Amprenavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Amprenavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
HIV-1 Protease dimer with Amprenavir (sticks) bound in the active site. PDB entry 3nu3 [1]

Example 11Synthesis of Amprenavir (1)To a solution of carbamate nitro derivative 15 (0.05 g, 0.09 mmol) in 2 mL of EtOAc was added SnCl2.2H2O (0.1 g, 0.5 mmol) at 70° C. The reaction mixture was heated for 1 h until starting material disappeared and the solution cooled to room temperature. It was then poured into saturated aq. NaHCO3 solution and extracted with EtOAc. The organic extract was dried over anhyd. Na2SO4 and concentrated under reduced pressure. It was purified over chromatography using petroleum ether:EtOAc (3:2) to give amprenavir 1 (0.04 g, 90%).IR: (CHCl3, cm−1): υmax 757, 1090, 1149, 1316, 1504, 1597, 1633, 1705, 2960, 3371; 1H NMR (200 MHz, CDC3): δ 0.86 (d, J=5.7 Hz, 3H), 0.90 (d, J=6.6 Hz, 3H), 1.78-2.21 (m, 3H), 235-3.11 (m, 6H), 3.58-4.11 (m, 7H), 4.25 (s, 2H), 5.01 (br s, 1H), 5.07 (br s, 1H), 6.65 (d, J=8.4 Hz, 2H), 7.20-7.28 (m, 5H), 7.51 (d, J=8.4 Hz, 2H); 13C NMR (50 MHz, CDC3): δ 19.9, 20.2, 27.3, 32.8, 35.4, 35.7, 53.8, 55.0, 58.6, 66.8, 72.6, 73.2, 75.3, 114.0, 125.9, 126.5, 1280.4, 129.5, 137.7, 150.9, 155.9; Anal. Calcd for C25H35N3O6S: C, 59.39; H, 6.98; N, 8.31; S, 6.34. Found: C, 59.36; H, 6.81; N, 8.25; S, 6.29%.

Process for synthesis of syn azido epoxide and its use as intermediate for the synthesis of amprenavir & saquinavir
US 20150011782 A1
Publication numberUS20150011782 A1
Publication typeApplication
Application numberUS 14/371,466
PCT numberPCT/IN2013/000021
Publication dateJan 8, 2015
Filing dateJan 10, 2013
Priority dateJan 10, 2012
Also published asWO2013105118A1, WO2013105118A8
InventorsSunita Khanderao Gadakh, Reddy Santhosh Rekula, Arumugam Sudalai
Original AssigneeCouncil Of Scientific & Industrial Research