- Simple and environment-friendly chemical synthesis method of 4-fluoro-2-methyl benzoic acid
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The invention relates to a simple and environment-friendly chemical synthesis method of 4-fluoro-2-methyl benzoic acid. According to the synthesis method, m-fluorotoluene and acetyl chloride are takenas starting raw materials, and are subjected to a Friedel-Crafts acylation reaction under the catalytic action of anhydrous aluminum trichloride, a haloform reaction is carried out with sodium hypochlorite, two isomers of 4-fluoro-2-methyl benzoic acid and 2-fluoro-4-methyl benzoic acid are simultaneously obtained after hydrolysis, and the isomers are separated through re-crystallizing so as to obtain the target product 4-fluoro-2-methylbenzoic acid. The route is mild in reaction condition, low in cost, environment-friendly and suitable for industrial production.
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Paragraph 0003
(2020/04/02)
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- Optimization of inhibitors of the tyrosine kinase EphB4. 2. Cellular potency improvement and binding mode validation by X-ray crystallography
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Inhibition of the tyrosine kinase erythropoietin-producing human hepatocellular carcinoma receptor B4 (EphB4) is an effective strategy for the treatment of solid tumors. We have previously reported a low nanomolar ATP-competitive inhibitor of EphB4 discovered in silico by fragment-based high-throughput docking combined with explicit solvent molecular dynamics simulations. Here we present a second generation of EphB4 inhibitors that show high inhibitory potency in both enzymatic and cell-based assays while preserving the appealing selectivity profile exhibited by the parent compound. In addition, respectable levels of antiproliferative activity for these compounds have been obtained. Finally, the binding mode predicted by docking and molecular dynamics simulations is validated by solving the crystal structures of three members of this chemical class in complex with the EphA3 tyrosine kinase whose ATP-binding site is essentially identical to that of EphB4.
- Lafleur, Karine,Dong, Jing,Huang, Danzhi,Caflisch, Amedeo,Nevado, Cristina
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supporting information
p. 84 - 96
(2013/02/23)
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- Novel 5-HT2A receptor ligands
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Compounds of formula I: are antagonists of the human 5-HT2A receptor, and hence useful in treatment or prevention of a variety of neurological conditions.
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Page/Page column 9
(2010/02/11)
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- FLUORINE CONTAINING BIOACTIVE HETEROCYCLES PART III : SYNTHESIS OF SOME NEW FLUORINE CONTAINING PHENYLGLYOXALS AND 1,2,4-TRIAZINE DERIVATIVES
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Some medicinally important new fluorine containing phenylglyoxals have been synthesized by selenium dioxide oxidation of appropriate fluorinated acetophenones and characterized by spectrum studies.The phenylglyoxals were treated with thiosemicarbazide to give corresponding thiosemicarbazones (III) which were cyclized, in situ, to yield 5-(fluorophenyl)-1,2,4-triazine-3(2H)-thiones.The 5-(4-fluorophenyl)-1,2,4-triazine-3-(2H)-thione (IV) undergoes nucleophilic displacement when refluxed with hydrazine hydrate to give corresponding 3-hydrazino-5-(4-fluorophenyl)-1,2,4-tria zine.The hydrazino derivative reacts with fluorinated 1,3-diketones, in glacial acetic acid yielding 5-(4-fluorophenyl)-3--1,2,4-triazines (VII).All synthesized compounds have been characterized on the basis of elemental analyses, ir, pmr and 19F nmr studies.
- Joshi, Krishna C.,Dubey, Kalpana,Dandia, Anshu
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p. 1545 - 1553
(2007/10/02)
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