1195768-06-9

Basic information

• Product Name: Dabrafenib Mesylate(GSK-2118436B)
• Synonyms: Dabrafenib Mesylate(GSK-2118436B);Dabrafenib Mesylate;GSK 2118436 Mesylate;GSK 2118436B;GSK2118436 Mesylate;GSK-2118436 Mesylate;Dabrafenib Mesylate (API);GSK 2118436 methanesulfonate salt
• CAS NO: 1195768-06-9
• Molecular Formula: CH₄O₃S*C₂₃H₂₀F₃N₅O₂S₂
• Molecular Weight: 615.6680696
• EINECS: 1592732-453-0
• Product Categories: Raf B protein kinase inhibitor
• Mol File: 1195768-06-9.mol
• Article Data: 6

Chemical Properties

• Appearance: /
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: DMSO (Slightly, Heated), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: Dabrafenib Mesylate(GSK-2118436B)(CAS DataBase Reference)
• NIST Chemistry Reference: Dabrafenib Mesylate(GSK-2118436B)(1195768-06-9)
• EPA Substance Registry System: Dabrafenib Mesylate(GSK-2118436B)(1195768-06-9)

Safety Data

• Hazardous Substances Data: 1195768-06-9(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 1195768-06-9 differently. You can refer to the following data:
1. Dabrafenib Mesylate is a salt form of Dabrafenib. Dabrafenib is an inhibitor of certain mutated forms of BRAF kinase, several of which may be associated with stimulating tumour growth (e.g. the BRAF V600E mutation), and Dabrafenib is also an inhibitor of BRAF V600-mutation positive cancer cell growth, both in vitro and in vivo.
2. Dabrafenib mesylate, sold by GlaxoSmithKline under the trade name Tafinlar, was approved by the U.S. FDA in May 2013 for the treatment of metastatic BRAF-mutant melanoma. Dabrafenib reversibly inhibits the BRAF(V600E) mutant kinase as a selective ATP-competitive inhibitor which results in tumor regression.

Definition

ChEBI: A methanesulfonate (mesylate) salt prepared from equimolar amounts of dabrafenib and methanesulfonic acid. Used for treatment of metastatic melanoma.

Synthesis

Commercially available fluoroaniline 40 was first converted to sulfonamide 42 in 91% yield by treatment with 2,5-difluorobenzenesulfonyl chloride (41) in the presence of pyridine. Next, deprotonation of 2-chloro-4-methylpyrimidine (43) with lithium bis(trimethylsilyl)amide (LHMDS) followed by addition to ester 42 afforded chloropyrimidine 44 in 72% yield. Bromination followed by thiazole formation through the use of 2,2-dimethylpropanethioamide gave the penultimate target 45 in 80% over two steps. Chloropyrimidine 45 was subjected to SNAr conditions with ammonium hydroxide to furnish the aminopyrimidine in 88% yield, and this was followed by exposure to methanesulfonic acid to afford dabrafenib mesylate (VI) in 85% yield.

references

[1]namba h, nakashima m, hayashi t, hayashida n, maeda s, rogounovitch ti, ohtsuru a, saenko va, kanematsu t, yamashita s. clinical implication of hot spot braf mutation, v599e, in papillary thyroid cancers. j. clin. endocrinol. metab. 2003; 88 (9): 4393–7. [2]tan yh, liu y, eu kw, ang pw, li wq, salto-tellez m, iacopetta b, soong r. detection of braf v600e mutation by pyrosequencing. pathology 2008; 40 (3): 295–8.[3]davies h, bignell gr, cox c, et al. mutations of the braf gene in human cancer. nature. 2002; 417: 949-954.[4]ma xh, piao sf, dey s, mcafee q, karakousis g, villanueva j, hart ls, levi s, hu j, zhang g, lazova r, klump v, pawelek jm, xu x, xu w, schuchter lm, davies ma, herlyn m, winkler j, koumenis c, amaravadi rk. targeting er stress-induced autophagy overcomes braf inhibitor resistance in melanoma. j clin invest. 2014; 124(3): 1406-17.

Upstream product

• 75-75-2 methanesulfonic acid 
• 1195765-45-7 dabrafenib 
• 60230-36-6 2,6-difluorobenzene-1-sulfonyl chloride 
• 1195768-20-7 N-(3-(2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide 
• 1195768-18-3 3-amino-2-fluorobenzoic acid methyl ester 
• 1195768-19-4 3-(2,6-difluorobenzenesulfonamido)-2-fluorobenzoic acid methyl ester 
• 1195768-23-0 N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1 ,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide 

Relevant articles and documents

COMBINATION OF RIBOCICLIB AND DABRAFENIB FOR TREATING OR PREVENTING CANCER

The present disclosure relates to pharmaceutical combinations comprising a cyclin dependent kinase 4/6 (CDK4/6) inhibitor compound, (b) a B-Raf inhibitor compound, and optionally (c) an alpha-isoform specific phosphatidylinositol 3 -kinase (PI3K) inhibitor compound, for the treatment or prevention of cancer, as well as related pharmaceutical compositions, uses, and methods of treatment or prevention of cancer.

Novel Crystal Form of Dabrafenib Mesylate and Preparation Method Thereof

Disclosed are a novel crystal form of Dabrafenib mesylate and preparation method thereof. The novel crystal form of the present invention is more stable in water or an aqueous system, and has greater solubility and dissolution in water, thus having better stability and bioavailability compared with the existing crystal forms.

COMBINATIONS OF AN ANTI-PD-L1 ANTIBODY AND A MEK INHIBITOR AND/OR A BRAF INHIBITOR

A novel combination comprising the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro- 4-iodo-phenylamino)6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3- d]pyrimidin-1 -yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and/or a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1 - dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, and an anti-PD-L1 antibody; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf and/or neutralizing or inhibiting the interaction between PD-L1 and its receptor, e.g. PD-1, is beneficial, eg. cancer.