937263-43-9

Usage

Uses

Used in Oncology:
Irbinitinib is used as an antineoplastic agent for the treatment of HER2+ cancers. It works by selectively binding to and inhibiting the phosphorylation of ErbB-2, preventing the activation of ErbB-2 signal transduction pathways and leading to growth inhibition and death of ErbB-2-expressing tumor cells.
Used in Pharmaceutical Industry:
Irbinitinib is used as a novel diarylamine ErbB inhibitor in the development of targeted cancer therapies. Its selective inhibition of ErbB-2 makes it a promising candidate for the treatment of cancers with ErbB-2 overexpression, offering an alternative treatment option for patients with HER2+ cancers.

References

Lee, P., et al. "In Vivo Activity of ARRY-380, a Potent, Small Molecule Inhibitor of ErbB2 in Combination with Trastuzumab, Docetaxel or Bevacizumab." Cancer Research 69.24 Supplement(2009):5104-5104. Moulder, S. L., et al. "Abstract A143: ARRY-380, a selective HER2 inhibitor: From drug design to clinical evaluation." Molecular Cancer Therapeutics 10.Supplement 1(2011):A143-A143. Dinkel, Victoria, et al. "Abstract 852: ARRY-380, a potent, small molecule inhibitor of ErbB2, increases survival in intracranial ErbB2+ xenograft models in mice." Cancer Research 72.8 Supplement(2012).

Upstream product

• 2131230-48-1 (E)-N'-(4-amino-2-cyanophenyl)-N,N-dimethylformimidamide 
• 19798-80-2 2-Amino-4-chloropyridine 
• 937263-71-3 4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylaniline 
• 1427452-48-9 7-chloro-[1,2,4]triazolo[1,5-a]pyridine 
• 39263-34-8 N′-(2-cyano-4-nitrophenyl)-N,N-dimethylformimidamide 
• 17420-30-3 5-nitroanthranilonitrile 
• 937263-44-0 7-(2-methyl-4-nitrophenoxy)-[1,2,4]triazolo[1,5-a] pyridine 
• 864244-98-4 4-(2-methyl-4-nitrophenoxy)pyridin-2-amine 
• 65370-42-5 4-chloro-2-nitropyridine 
• 99-53-6 2-methyl-4-nitrophenol 
• 1429755-58-7 1-(4-((4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)-3-(1-hydroxy-2-methylpropan-2-yl)thiourea 

Relevant academic research and scientific papers

Preparation method of tucatinib

The invention relates to a preparation method of tucatinib. The method comprises the following steps: by taking 4-hydroxy-6-chloroquinazoline as a raw material, firstly carrying out copper-catalyzed C-N cross-coupling reaction on the 4-hydroxy-6-chloroquinazoline and 2-amino-4, 4-dimethyl-4, 5-dihydrooxazole, then activating the 4-hydroxy of quinazolinone by adopting a BOP, and enabling product and 4-([1, 2, 4] triazolo [1, 5-a] pyridine-7-yloxy)-3-methylaniline to be subjected to a nucleophilic substitution reaction to obtain tucatinib. With the method, using of high-corrosivity and high-toxicity reagents is avoided, and the method has low requirements on equipment, the operation difficulty and environmental protection requirements are reduced, and the method has the advantages of high product yield and high product purity; the process is simple and environment-friendly and suitable for large-scale production.

Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models

HER2 is a transmembrane tyrosine kinase receptor that mediates cell growth, differentiation, and survival. HER2 is overexpressed in approximately 20% of breast cancers and in subsets of gastric, colorectal, and esophageal cancers. Both antibody and smallm

New Synthetic Route to Tucatinib

A new and improved synthetic route to tucatinib is described that involves three key intermediates. The first of these, 4-([1,2,4]triazolo[1,5- a ]pyridin-7-yloxy)-3-methylaniline, was prepared on a 100 g scale in 33percent yield over five steps and 99percent purity. Next, N 4 -(4-([1,2,4]triazolo[1,5- a ]pyridin-7-yloxy)-3-methylphenyl)quinazoline-4,6-diamine was isolated in 67percent yield over three steps and >99percent purity. Then, 4,4-dimethyl-2-(methylthio)-4,5-dihydrooxazole trifluoromethanesulfonate was prepared under mild conditions in 67percent yield over two steps. Finally, tucatinib was obtained in 17percent yield over nine steps and in >99percent purity (HPLC). Purification methods used to isolate the product and the intermediates involved in the route are also reported.

Irbinitinib intermediates for preparation of (by machine translation)

The invention belongs to the organic synthesis and bulk drug preparation technology field, in particular to the treatment of breast cancer drug Irbinitinib preparation method and intermediate, comprising the steps of: 2 - methyl - 4 - nitro-phenol (formul

Solid dispersions of a ERB2 (HER2) inhibitor

A solid dispersion of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and processes for preparing the solid dispersion are provided herein. Also, a pharmaceutical composition comprising a solid dispersion of N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and uses thereof are provided herein.

TREATMENT OF BRAIN CANCER

Compounds for the treatment of brain cancer are provided herein. Pharmaceutical compositions comprised of those compounds for the treatment of brain cancer are also provided herein.

SOLID DISPERSION

A solid dispersion of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and processes for preparing the solid dispersion are provided herein. Also, a pharmaceutical composition comprising a solid dispersion of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and uses thereof are provided herein.

Processes and intermediates for the preparation of N4-phenyl-quinazoline-4-amine derivatives

This invention provides compounds of Formula (I), wherein B, G, A, E, R1, R2, R3, m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.