1188271-29-5

Upstream product

• 5424-21-5 2,4-dichloro-6-methylpyrimidine 
• 108593-44-8 methyl 3-methoxy-5-methylbenzoate 
• 585-81-9 3-hydroxy-5-methylbenzoic acid 

Downstream Products

• 1188271-30-8 (S)-2-(2-chloro-6-((2-hydroxypropyl)amino)pyrimidin-4-yl)-1-(3-methoxy-5-methylphenyl)ethanone 
• 1188271-31-9 (S)-1-((2-chloro-6-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)propan-2-ol 
• 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

Synthesis and biological evaluation of new pyrimidine-4-yl-ethanol derivatives as ROS1 kinase inhibitors

As a part of trials to target ROS1 kinase with potential inhibitors, a novel series of pyrimidin-4-yl-ethanol and ethanone derivatives (4a-f, 5a-f, 6a-f and 7a-f) have been designed based on previously discovered lead compounds KIST301072 and KIST301080, and synthesized on 4-5 steps according to compounds. The structures of the newly synthesized compounds have been confirmed on 1H-NMR, 13C-NMR and IR. Most of the tested compounds showed ROS1 kinase inhibitory activity in micromolar range.

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.

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.

Synthesis and biological evaluation of new pyrazol-4-ylpyrimidine derivatives as potential ROS1 kinase inhibitors

With the aim of discovering potent and selective kinase inhibitors targeting ROS1 kinase, we designed, synthesized and screened a series of new pyrazol-4-ylpyrimidine derivatives based on our previously discovered lead compound KIST301072. Compounds 6a-e and 7a-e showed good to excellent activities against ROS1 kinase, and seven out of tested compounds were more potent than KIST301072. Compound 7c was the most potent with IC50 of 24 nM. Moreover, compound 7c showed ROS1 inhibitory selectivity of about 170-fold, relative to that of ALK sharing about 49% amino acid sequence homology with ROS1 kinase in the kinase domain. In silico modeling of 7c at ROS1 active site revealed some essential features for ROS1 inhibitory activity. Based on this study as well as the previous studies, we could build a hypothetical model predicting the required essential features for ROS1 inhibitory activity. The model validity has been tested through a second set of compounds.

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