444731-74-2

Usage

Uses

Used in Pharmaceutical Industry:
N-(2-chloropyrimidin-4-yl)-2,3-dimethyl-2H-indazol-6-amine is used as an impurity in the production of Pazopanib (P210925) for its role in targeting VEGFR and PDGFR. N-(2-chloropyriMidin-4-yl)-2,3-diMethyl-2Hindazol-6-aMine is relevant in the development and formulation of Pazopanib as an oral angiogenesis inhibitor, which is crucial for its effectiveness in treating cancer.
N-(2-chloropyriMidin-4-yl)-2,3-diMethyl-2Hindazol-6-aMine's presence as an impurity in Pazopanib highlights its importance in the pharmaceutical industry, particularly in the context of cancer treatment. It is essential to monitor and control the levels of this impurity to ensure the safety and efficacy of Pazopanib as a therapeutic agent.

InChI:InChI=1/C13H12ClN5/c1-8-10-4-3-9(7-11(10)18-19(8)2)16-12-5-6-15-13(14)17-12/h3-7H,1-2H3,(H,15,16,17)

Upstream product

• 3934-20-1 2,6-Dichloropyrimidine 
• 444731-72-0 2,3-dimethyl-6-amino-2H-indazole 
• 635702-60-2 2,3-dimethyl-2H-indazole-6-amine hydrochloride 
• 635702-59-9 3-methyl-6-nitro-1H-indazole sulfate 
• 444731-73-1 2,3?dimethyl?6?nitro?2H?indazole 
• 6494-19-5 3-methyl-6-nitro-1H-indazole 

Downstream Products

• 444731-75-3 N-(2-chloropyrimidin-4-yl)-N-methyl-2,3-dimethyl-2H-indazole-6-amine 
• 1307297-62-6 N⁴-(2,3-dimethyl-2H-indazol-6-yl)-N²-(3-fluorophenyl)-N⁴-methylpyrimidine-2,4-diamine 
• 1307297-61-5 N²-(3-bromophenyl)-N⁴-(2,3-dimethyl-2H-indazol-6-yl)-N⁴-methylpyrimidine-2,4-diamine 
• 1307297-65-9 N²-(3-chlorophenyl)-N⁴-(2,3-dimethyl-2H-indazol-6-yl)-N⁴-methylpyrimidine-2,4-diamine 
• 1307297-63-7 N⁴-(2,3-dimethyl-2H-indazol-6-yl)-N²-(3-methoxyphenyl)-N⁴-methylpyrimidine-2,4-diamine 
• 1307297-66-0 N⁴-(2,3-dimethyl-2H-indazol-6-yl)-N²-(3,5-dimethylphenyl)-N⁴-methylpyrimidine-2,4-diamine 
• 1307297-69-3 N⁴-(2,3-dimethyl-2H-indazol-6-yl)-N⁴-methyl-N²-(4-(methylthio)phenyl)pyrimidine-2,4-diamine 
• 1307297-68-2 N⁴-(2,3-dimethyl-2H-indazol-6-yl)-N⁴-methyl-N²-(4-(trifluoromethoxy)phenyl)pyrimidine-2,4-diamine 
• 635702-64-6 pazopanib hydrochloride 
• 444731-52-6 pazopanib 
• 635702-65-7 5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzenesulfonamide methanesulfonic acid salt 
• 1226499-98-4 N2,N4-bis(2,3-dimethyl-2H-indazol-6-yl)-pyrimidine-2,4-diamine 
• 1296888-47-5 (2,3-dimethyl-2H-indazol-6-yl)-(2-methoxypyrimidin-4-yl)methylamine 

Relevant academic research and scientific papers

Discovery of Novel Pazopanib-Based HDAC and VEGFR Dual Inhibitors Targeting Cancer Epigenetics and Angiogenesis Simultaneously

Herein a novel series of pazopanib hybrids as polypharmacological antitumor agents were developed based on the crosstalk between histone deacetylases (HDACs) and vascular endothelial growth factor (VEGF) pathway. Among them, one ortho-aminoanilide 6d and one hydroxamic acid 13f exhibited considerable total HDACs and VEGFR-2 inhibitory activities. The HDAC inhibitory activities endowed 6d and 13f with potent antiproliferative activities, which was not observed in the approved VEGFR inhibitor pazopanib. Compounds 6d and 13f possessed comparable HDAC isoform selectivity profiles to the clinical class I HDAC inhibitor MS-275 and the approved pan-HDAC inhibitor SAHA, respectively. 6d and 13f also exhibited uncompromised multiple tyrosine kinases inhibitory activities relative to pazopanib. The intracellular dual inhibition to HDAC and VEGFR of 6d and 13f was validated by Western blot analysis. In both HUVECs tube formation assay and rat thoracic aorta rings assay, 6d and 13f showed comparable antiangiogenic potencies to pazopanib. What's more, 6d possessed desirable pharmacokinetic profiles with the oral bioavailability of 72% in SD rats and considerable in vivo antitumor efficacy in a human colorectal adenocarcinoma (HT-29) xenograft model.

Preparation, biological & cheminformatics-based assessment of N2,N4-diphenylpyrimidine-2,4-diamine as potential Kinase-targeted antimalarials

Twenty eight new N2,N4-diphenylpyrimidine-2,4-diamines have been prepared in order to expand our understanding of the anti-malarial SAR of the scaffold. The aim of the study was to make structural modifications to improve the overall

High Turnover Pd/C Catalyst for Nitro Group Reductions in Water. One-Pot Sequences and Syntheses of Pharmaceutical Intermediates

Commercially available Pd/C can be used as a catalyst for nitro group reductions with only 0.4 mol % Pd loading. The reaction can be performed using either silane as a transfer hydrogenating agent or simply a hydrogen balloon (μ1 atm pressure). With this technology, a series of nitro compounds was reduced to the desired amines in high chemical yields. Both the catalyst and surfactant were recycled several times without loss of reactivity.

Pazopanib structure based HDAC (histone deacetylase) and VEGFR (vascular endothelial growth factor receptor) dual-target inhibitor and preparation method and application thereof

The invention relates to a pazopanib structure based HDAC (histone deacetylase) and VEGFR (vascular endothelial growth factor receptor) dual-target inhibitor and a preparation method and application thereof. The compound has structures as are shown in formula I, formula II or formula III. The invention further provides a preparation method of the compounds and application of the compounds in preparing drugs for prevention or treatment of cancer-related diseases.

Synthesis and characterization of four process impurities in pazopanib

Pazopanib (trade name Votrient) is a potent and selective multi-targeted tyrosine kinase inhibitor that blocks tumor growth and inhibits angiogenesis. Based on a recently reported procedure, we herein report the first synthesis of four potential process impurities generated in the production of pazopanib. The structure of these impurities were synthesized and characterized by 1H NMR, 13C NMR and HRMS data. The possible formation mechanisms of these impurities were also elucidated. These findings should be useful for the quality control of pazopanib in manufacture.

AN IMPROVED PROCESS FOR THE PREPARATION OF PAZOPANIB OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

The present invention is relates to an improved process for the preparation of pazopanib or a pharmaceutically acceptable salts thereof. The present invention also relates to novel polymorphic Forms of pazopanib hydrochloride, and its intermediates thereo

PROCESS FOR THE PREPARATION OF PAZOPANIB OR SALTS THEREOF

The present invention provides a process for the preparation of pazopanib of Formula Ia or salts, and intermediates thereof.

Pyrimidineamines as angiogenesis modulators

Pyrimidine derivatives, which are useful as VEGFR2 inhibitors are described herein. The described invention also includes methods of making such pyrimidine derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

Design, synthesis and biological evaluation of pazopanib derivatives as antitumor agents

A novel series of pazopanib derivatives were designed, synthesized, and evaluated for their inhibitory activity against a series of kinases including VEGFR-2, EGFR, AKT1, ALK1, and ABL1. The anti-angiogenic activities ex vivo of some compounds were also investigated. Compounds P2d and P2e demonstrated outstanding inhibitory activity against VEGFR-2 and ABL1 and higher anti-angiogenic activity compared with Pazopanib, the reference standard. These two compounds (P2d and P2e) could be used as novel lead compounds for further development of anticancer agents.

Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents

A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by 1H NMR and MS. Their inhibitory