1188271-31-9

Upstream product

• 1188271-30-8 (S)-2-(2-chloro-6-((2-hydroxypropyl)amino)pyrimidin-4-yl)-1-(3-methoxy-5-methylphenyl)ethanone 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 108593-44-8 methyl 3-methoxy-5-methylbenzoate 
• 5424-21-5 2,4-dichloro-6-methylpyrimidine 
• 585-81-9 3-hydroxy-5-methylbenzoic acid 
• 1188271-29-5 2-(2,6-dichloropyrimidin-4-yl)-1-(3-methoxy-5-methylphenyl)ethanone 

Downstream Products

• 1188271-32-0 (S)-2-(4-(2-chloro-6-(2-hydroxypropylamino)pyrimidin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetonitrile 
• 1188271-33-1 [4-[6-(2(S)-hydroxypropylamino)-2-pyridin-3-yl-pyrimidin-4-yl]-3-(3-methoxy-5-methylphenyl)-pyrazol-1-yl]acetonitrile 
• 1188271-28-4 KIST₃₀₁₀₇₂ 
• 1262110-32-6 [4-[6-(2(S)-acetoxypropylamino)-2-pyridin-3-yl-pyrimidin-4-yl]-3-(3-acetoxy-5-methylphenyl)-pyrazol-1-yl]acetonitrile 

Relevant academic research and scientific papers

2,4,6-Trisubstituted pyrimidine compounds for ROS kinase inhibitors

The present invention relates to new 2,4,6-trisubstituted pyrimidine compounds and pharmaceutically permissible salts thereof, a manufacturing method thereof, and medical uses as anticancer drugs therefor. According to the present invention, the new compounds have excellent activation with respect to ROS kinase enzymes, and thus useful for anticancer drugs to treat and prevent diseases such as CNS related cancer, meningioma, astrocytoma, glioblastoma multiforme, NSCLC, etc.

Structure-based optimization and biological evaluation of trisubstituted pyrazole as a core structure of potent ROS1 kinase inhibitors

Recently inhibition of ROS1 kinase has proven to be a promising strategy for several indications such as glioblastoma, non-small cell lung cancer (NSCLC), and cholangiocarcinoma. Our team reported trisubstituted pyrazole-based ROS1 inhibitors by which two inhibitors showed good IC50 values in enzyme-based screening. To develop more advanced ROS1 inhibitors through SAR this trisubstituted pyrazole-based scaffold has been built. Consequently, 16 compounds have been designed, synthesized and shown potent IC50 values in the enzymatic assay, which are from 13.6 to 283 nM. Molecular modeling studies explain how these ROS1 kinase inhibitors revealed effectively the key interactions with ROS1 ATP binding site. Among these compounds, compound 9a (IC50 = 13.6 nM) has exerted 5 fold potency than crizotinib and exhibited high degree of selectivity (selectivity score value = 0.028) representing the number of non-mutant kinases with biological activity over 90% at 10 μM.

PYRAZOLE COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST ROS KINASE

Disclosed herein are novel pyrazole compounds, pharmaceutically acceptable salts thereof, a method for preparing the same, and uses thereof as anticancer agents.

Design, synthesis and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor

ROS1 protein is a receptor tyrosine kinase that has been reported mainly in meningiomas and astrocytomas, and until now, there is no selective inhibitor for this kinase. In this study, we illustrate for the synthesis of a highly potent and selective inhib