1029872-54-5 Usage
Uses
Vemurafenib selective BRAFV600E kinase inhibitor; an antitumor agent. Vemurafenib functions by inhibiting the proliferation and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase and ERK phosphorylation in a panel of tumor cell lines, including melanoma cell lines expressing BRAFV600E or other mutant BRAF proteins altered at codon 600. Potent B-Raf inhibitor
Clinical Use
Vemurafenib was originally discovered at Plexxikon and has
been co-developed by Roche and Plexxikon as an oral BRAF
inhibitor for the treatment of patients with BRAFV600E mutation-
positive metastatic melanoma. The drug displays good potency
and selectivity for the V600E mutation (IC50 = 3.2–14 nM), an
oncoprotein, over the wild-type BRAF (IC50 = 21–370 nM). The
compound is less potent in in vitro kinase assays than other Plexxikon
BRAF inhibitors, but it was selected for clinical development based on its enhanced potency against the BARFV600E-containing
A374 melanoma cell line.
Synthesis
The synthesis described below is
based on a recent process patent (the Scheme).Commercially available 2-amino-5-bromopyridine (271) was
treated with 4-chlorophenylboronic acid (272) in the presence of
Na2CO3 and a catalytic amount of Pd(OAc)2/PdCl2(dppf)CH2Cl2 to
give Suzuki product 273 in 83% yield. Arene 273 was subjected
to iodination conditions using NIS and TFA to provide iodide 274
in 98% yield. Iodide 274 and pinacol vinylboronate 275 were coupled
under Suzuki conditions followed by treatment with acid to
affect a tandem coupling–cyclization sequence which resulted in
pyrimidyl pyrrole 276 in good yield. This material was treated with
aluminum trichloride and then subjected to the the acyl chloride of
commercially available sulfonamide acid 277, triggering a Friedel-
Crafts reaction providing vemurafenib (XXIV) in 85% yield.
Drug interactions
Potentially hazardous interactions with other drugs
Anticoagulants: possibly enhances anticoagulant
effect of warfarin.
Antipsychotics: avoid concomitant use with
clozapine, risk of agranulocytosis.
Oestrogens and progestogens: contraceptive effect
possibly reduced.
Metabolism
Only 5% of a dose of vemurafenib is metabolised. 94% of the dose is excreted in the faeces and 1% in the urine.
Check Digit Verification of cas no
The CAS Registry Mumber 1029872-54-5 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,2,9,8,7 and 2 respectively; the second part has 2 digits, 5 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 1029872-54:
(9*1)+(8*0)+(7*2)+(6*9)+(5*8)+(4*7)+(3*2)+(2*5)+(1*4)=165
165 % 10 = 5
So 1029872-54-5 is a valid CAS Registry Number.
1029872-54-5Relevant articles and documents
Simple preparation method of vemurafenib and analogues thereof
-
, (2019/10/02)
The invention provides a simple preparation method of vemurafenib and analogues thereof. The method includes: subjecting para-substituted phenylacetaldehyde II and N-[2, 4-disubstituted-3-(cyanopropionyl)phenyl]n-propanesulfonamide III to azeotropic dewatering and condensation reaction under alkaili catalysis, condensing the obtained condensation product and the methylenation reagent V(N, N-dimethylformamide or tri-orthoformate), and then performing cyclization with ammonia to obtain vemurafenib or analogues thereof. The method for preparation of vemurafenib provided by the invention has the characteristics of low cost, mild process conditions, low operation requirements, short reaction time, high production efficiency, simple process operation, little waste water production, green and environmental protection, high yield and purity, and is beneficial to green industrial production of vemurafenib. At the same time, the method provided by the invention can prepare vemurafenib analogues,and is of important significance for the drug efficacy study of similar compounds.
SUBSTANTIALLY PURE VEMURAFENIB AND ITS SALTS
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Paragraph 0126-0127, (2018/12/04)
The present invention relates to a process for the preparation substantially pure propane-1-sulfonicacid-{3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide or Vemurafenib of Formula (I). The present invention further relates to a process for the preparation substantially pure propane-1-sulfonic acid-{3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3 -b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide trifluoro methane sulfonic acid salt or Vemurafenib triflate of Formula (VII)
NOVEL PROCESSES FOR THE PREPARATION OF VEMURAFENIB
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, (2015/06/08)
The present invention provides novel intermediates of vemurafenib or a pharmaceutically acceptable salt thereof and processes for its preparation. The present invention also provides novel processes for preparation of vemurafenib or a pharmaceutically acceptable salt thereof using the novel intermediates.
