1175296-50-0

Basic information

• Product Name: (1S)-1-(2,6-dichloro-3-fluorophenyl)ethyl methanesulfonate
• Synonyms: (1S)-1-(2,6-dichloro-3-fluorophenyl)ethyl methanesulfonate
• CAS NO: 1175296-50-0
• Molecular Weight: 287.139
• Mol File: 1175296-50-0.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: (1S)-1-(2,6-dichloro-3-fluorophenyl)ethyl methanesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: (1S)-1-(2,6-dichloro-3-fluorophenyl)ethyl methanesulfonate(1175296-50-0)
• EPA Substance Registry System: (1S)-1-(2,6-dichloro-3-fluorophenyl)ethyl methanesulfonate(1175296-50-0)

Safety Data

• Hazardous Substances Data: 1175296-50-0(Hazardous Substances Data)

Upstream product

• 290835-85-7 2',6'-dichloro-3'-fluoroacetophenone 
• 756520-66-8 1-(2,6-dichloro-3-fluorophenyl)ethanol 
• 877397-65-4 (S)‐1‐(2,6-dichloro-3-fluorophenyl)ethanol 
• 124-63-0 methanesulfonyl chloride 

Downstream Products

• 1212065-90-1 (1R)-1-(2,6-dichloro-3-fluorophenyl)ethan-1-amine 
• 1394930-83-6 2-amino-5-bromo-N-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethyl]pyridine-3-carboxamide 
• 1394930-47-2 C₂₂H₂₂Cl₂FN₅O₂ 

Relevant articles and documents

Discovery of 2-aminopyridines bearing a pyridone moiety as potent ALK inhibitors to overcome the crizotinib-resistant mutants

Despite the initial benefit demonstrated in clinical setting with ALK inhibitors, the challenging resistant mutants (F1174L, L1196M and G1202R) invariably developed. In this work, a series of 2-aminopyridine derivatives were designed and synthesized by C-5 position incorporation of a 2-pyridone moiety and bioisosteric replacement of the C-3 position linkers. Optimization of the 2-aminopyridine derivatives led to the identification of hit 18d displaying a significant growth inhibition against a variety of ALK-addicted cancer cells. Especially in the case of ALK-positive Karpas-299 cell, 18d exhibited excellent anti-proliferative potency with an IC50 value of about 40 nM. Moreover, 18d demonstrated encouraging activities against wild-type ALK (19 nM), ROS1 (2.3 nM) as well as challenging crizotinib-resistant ALKL1196M and ALKG1202R mutants with IC50 values of 45 nM and 22 nM, respectively. Additionally flow cytometric analysis indicates that 18d inhibited Karpas-299 cell viability via G1 phase arrest. Taken together, this work provided a promising ALK inhibitor to circumvent the clinical crizotinib-resistant mutants.

Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors

A series of 2-amino-N-benzylpyridine-3-carboxnamides, 2-amino-N- benzylpyridine-3-sulfonamides and 2-amino-3-benzylthiopyridines against c-Met were designed by means of bioisosteric replacement and docking analysis. Optimization of the 2-amino-3-benzylthiopyridine scaffold led to the identification of compound (R)-10b displaying c-Met inhibition with an IC 50 up to 7.7 nM. In the cytotoxic evaluation, compound (R)-10b effectively inhibited the proliferation of c-Met addictive human cancer cell lines (IC50 from 0.19 to 0.71 μM) and c-Met activation-mediated cell metastasis. At a dose of 100 mg/Kg, (R)-10b evidently inhibited tumor growth (45%) in NIH-3T3/TPR-Met xenograft model. Of note, (R)-10b could overcome c-Met-activation mediated gefitinib-resistance, which indicated its potential use for drug combination. Taken together, 2-amino-3-benzylthiopyridine scaffold was first disclosed and exhibited promising pharmacological profiles against c-Met, which left room for further exploration.

FUSED BICYCLIC KINASE INHIBITORS

Compounds of Formula I, as shown below and defined herein: pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including treatment of cancers, such as but not limited to tumors driven at least in part by at least one of RON, MET, IR, IGF-1 R, or ALK. This Abstract is not limiting of the invention.