366016-82-2

Upstream product

• 391202-17-8 1-[4-(4-methoxyphenyl)butan-1-yl]-1H-1,2,3-triazole methanesulfonate 
• 7440-44-0 pyrographite 
• 391202-25-8 1-[4-(4-tert-butoxyphenyl)butan-1-yl]-1H-1,2,3-triazole 
• 52999-15-2 4-(p-methoxyphenyl)-3-butyn-1-ol 
• 52244-70-9 4-(4-methoxyphenyl)butan-1-ol 
• 81786-51-8 1-methanesulfonyloxy-4-(4-methoxyphenyl)butane 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 391202-16-7 1-(4-(4-methoxyphenyl)butyl)-1H-1,2,3-triazole 
• 88537-45-5 4-Methylphenylsulfonic acid 4-(4-methoxyphenyl)butyl ester 
• 100-66-3 methoxybenzene 
• 40877-19-8 4-chloro-1-(4-methoxyphenyl)butan-1-one 
• 568594-83-2 1-(4-methoxyphenyl)-4-(1H-1,2,3-triazol-1-yl)-1-butanone 

Downstream Products

• 767329-14-6 1-[4-(4-{2-[2-(4-methoxy-phenyl)-vinyl]-oxazol-4-ylmethoxy}-phenyl)-butyl]-1H-[1,2,3]triazole 
• 767329-28-2 1-[4-(4-{2-[2-(4-difluoromethoxy-phenyl)-vinyl]-oxazol-4-ylmethoxy}-phenyl)-butyl]-1H-[1,2,3]triazole 
• 767329-35-1 1-(4-{4-[2-(2-benzo[1,3]dioxol-5-yl-vinyl)-oxazol-4-ylmethoxy]-phenyl}-butyl)-1H-[1,2,3]triazole 
• 767329-48-6 1-[4-(4-{2-[2-(2,2-difluoro-benzo[1,3]dioxol-5-yl)-vinyl]-oxazol-4-ylmethoxy}-phenyl)-butyl]-1H-[1,2,3]triazole 
• 864548-44-7 1-[4-(4-{2-[(E)-2-(4-trifluoromethanesulfinyl-phenyl)-vinyl]-thiazol-4-ylmethoxy}-phenyl)-butyl]-1H-[1,2,3]triazole 
• 887612-84-2 N-{4-[4-(4-[1,2,3]Triazol-1-yl-butyl)-phenoxymethyl]-thiazol-2-yl}-acetamide 

Relevant academic research and scientific papers

A Facile Total Synthesis of Mubritinib

A five-step, practical, and concise total synthesis of mubritinib is described. The synthesis utilized Friedel-Crafts acylation, click reaction, reduction, and demethylation for the construction of the triazole ring system as key steps. Another important feature of this synthesis is the Bredereck oxazole synthesis. The main advantages of this process are the improved yield and decreased number of reaction steps, which paves the way for the industrial-scale synthesis of mubritinib.

Identification of a novel toxicophore in anti-cancer chemotherapeutics that targets mitochondrial respiratory complex i

Disruption of mitochondrial function selectively targets tumour cells that are dependent on oxidative phosphorylation. However, due to their high energy demands, cardiac cells are disproportionately targeted by mitochondrial toxins resulting in a loss of cardiac function. An analysis of the effects of mubritinib on cardiac cells showed that this drug did not inhibit HER2 as reported, but directly inhibits mitochondrial respiratory complex I, reducing cardiac-cell beat rate, with prolonged exposure resulting in cell death. We used a library of chemical variants of mubritinib and showed that modifying the 1H-1,2,3-triazole altered complex I inhibition, identifying the heterocyclic 1,3-nitrogen motif as the toxicophore. The same toxicophore is present in a second anti-cancer therapeutic carboxyamidotriazole (CAI) and we demonstrate that CAI also functions through complex I inhibition, mediated by the toxicophore. Complex I inhibition is directly linked to anti-cancer cell activity, with toxicophore modification ablating the desired effects of these compounds on cancer cell proliferation and apoptosis.

Synthesis method of mubritinib triazole intermediate

The invention discloses a method for synthesizing a mubritinib triazole intermediate by taking propiolic acid as a raw material through a Click reaction. The method comprises the following steps: 1, taking anisole as a raw material, and carrying out a Friedel-Crafts acylation reaction with 4-chlorobutyryl chloride to obtain gamma-chloro-4-methoxyphenylbutanone, 2, enabling the gamma-chloro-4-methoxyphenylbutanone to react with sodium azide, propiolic acid, a copper catalyst, sodium ascorbate, an alkali and a solvent, so as to obtain 1-(4-methoxyphenyl)-4-(1H-1, 2, 3-triazole-1-yl)-1-butanone,3, reducing carbonyl into methylene by 1-(4-methoxyphenyl)-4-(1H-1, 2, 3-triazole-1-yl)-1-butanone in a trifluoroacetic acid/triethylsilane system, and 4, carrying out demethylation on the 1-[4-(4-methoxyphenyl)butyl]-1H-1, 2, 3-triazole by using 40% hydrobromic acid to obtain the mubritinib intermediate 4-[4-(1H-1, 2, 3-triazole-1-yl)butyl]phenol. The method greatly shortens the reaction path, and has the advantages of accessible raw materials, mild reaction conditions, high yield and the like, and is simple to operate.

HETEROCYCLIC MITOCHONDRIAL ACTIVITY INHIBITORS AND USES THEREOF

Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (A/K), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.

Preventive/therapeutic method for cancer

This invention provides a prophylactic or therapeutic method for cancer. A prophylactic or therapeutic method for cancer, which is characterized by selectively inhibiting ErbB-2 (HER2) to block information signals of multimers of the epithelial growth factor receptor family.

Method for producing 1-substituted-1,2,3- triazole derivative

A method for producing a compound of the formula: (1) in a secondary or tertiary alcohol in the presence of a base, or (2) in the absence of a base is provided. According to this method, a 1-substituted-1,2,3-triazole compound having a tyrosine kinase inhibitory action can be produced efficiently in a high yield at an industrial large scale by a convenient method

MEDICINAL COMPOSITIONS IMPROVED IN SOLUBLITY IN WATER

Solid dispersions are provided comprising an HER2 inhibitor which is hardly or not soluble in water and a hydrophilic polymer. These solid dispersions have been improved in the solubility of the HER2 inhibitor, oral absorption and bioavailability in blood

MEDICINAL COMPOSITIONS HAVING IMPROVED ABSORBABILITY

An HER2 inhibitor having an average particle size of about 3 μm or less or a composition containing the same which has improved HER2 inhibitor-absorbability.

Heterocyclic compounds their production and use

A compound represented by the formula: wherein m is 1 or 2, R1 is a halogen or an optionally halogenated C1-2 alkyl; one of R2 and R3 is a hydrogen atom and the other is a group represented by the formula: wherein n is 3 or 4; R4 is a C1-4 alkyl group substituted by 1 or 2 hydroxy groups, or a salt thereof shows tyrosine kinase-inhibiting activity.