496775-62-3 Usage
Uses
Treatment of chemotherapy-induced thrombocytopenia and treatment of immune thrombocytopenic purpura.
Clinical Use
Eltrombopag olamine, a thrombopoietin receptor (TpoR) agonist,
was approved in late 2008 for the once-daily, oral short-term and long-term treatment of adult patients with previously treated
chronic idiopathic thrombocytopenic purpura (ITP). It is the first
small-molecule TpoR agonist and was launched in the U.S. for this
indication in 2009 by GlaxoSmithKline (GSK). Because eltrombopag
is a small molecule, the drug is administered orally and has
a reduced potential for causing an immune system reaction
versus alternative protein-based therapies. In 2010, eltrombopag
was approved in Europe for the long-term treatment of adult
patients with previously treated chronic ITP.
Synthesis
The synthesis began
with the nitration of 2-bromophenol (39) with sodium nitrate
and sulfuric acid in water at 10°C to give 2-bromo-6-nitrophenol
(40) in 25% yield, which was methylated using methyl iodide and
potassium carbonate in refluxing acetone providing 2-bromo-
6-nitroanisole (41) in 76% yield (the Scheme).40 Suzuki coupling of
compound 41 with 3-carboxyphenyl boronic acid with Pd(PPh3)4
and 2 M sodium carbonate in refluxing dioxane gave 20-methoxy-
30-nitrobiphenyl-3-carboxylic acid (42) in 47% yield as a tan
powder. Demethylation using 48% HBr (aq) in refluxing acetic acid
resulted in a 79% yield of 20-hydroxy-30-nitrobiphenyl-3-carboxylic
acid (43). The nitro group of compound 43 was reduced via catalytic
hydrogenation at 50 psi at room temperature over Pd/C in
mixed ethanol/3 M aq NaOH solution to give 30-amino-20-hydroxybiphenyl-
3-carboxylic acid (44) in quantitative yield. The
intermediate 1-(3,4-dimethylphenyl)-3-methyl-2,5-dihydro-1Hpyrazol-
5-one (47) was prepared by condensing of 3,4-dimethylphenyl-
hydrazine 45 with ethyl acetoacetate 46 with sodium
acetate in refluxing acetic acid in 76% yield. Treatment of (44) with
sodium nitrite in 1 M HCl at 5°C, followed by condensation with
1-(3,4-dimethylphenyl)-3-methyl-2,5-dihydro-1H-pyrazol-5-one
(47) at a constant pH of 7–8 via the addition of sodium bicarbonate
and ethanol afforded eltrombopag in 32% yield. Finally, eltrombopag
was treated with hydroxyl ethylamine to give eltrombopag
olamine (VIII).
Check Digit Verification of cas no
The CAS Registry Mumber 496775-62-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,9,6,7,7 and 5 respectively; the second part has 2 digits, 6 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 496775-62:
(8*4)+(7*9)+(6*6)+(5*7)+(4*7)+(3*5)+(2*6)+(1*2)=223
223 % 10 = 3
So 496775-62-3 is a valid CAS Registry Number.
InChI:InChI=1/C25H22N4O4.2C2H7NO/c1-14-10-11-19(12-15(14)2)29-24(31)22(16(3)28-29)27-26-21-9-5-8-20(23(21)30)17-6-4-7-18(13-17)25(32)33;2*3-1-2-4/h4-13,26,30H,1-3H3,(H,32,33);2*4H,1-3H2/b27-22-;;
