15191-69-2

Upstream product

• 579-74-8 2-Methoxyacetophenone 
• 383-63-1 ethyl trifluoroacetate, 

Downstream Products

• 1335246-16-6 4-(5-(2-hydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide 
• 1335246-21-3 methyl 4-(5-(2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzoate 
• 1335246-18-8 4-(5-(2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzoic acid 
• 1402003-92-2 5-(2-methoxyphenyl)-3-(trifluoromethyl)isoxazole 
• 439107-58-1 C₁₄H₉F₃N₂OS 
• 439097-26-4 C₁₄H₉F₃N₂O₂ 
• 1581726-11-5 C₂₀H₁₈F₃N₃O₃S 
• 1581726-20-6 C₁₆H₁₂F₃N₃O₂S 

Relevant academic research and scientific papers

An SAR study of hydroxy-trifluoromethylpyrazolines as inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader assay

The proteins Orai1 and STIM1 control store-operated Ca2+ entry (SOCE) into cells. SOCE is important for migration, invasion and metastasis of MDA-MB-231 human triple negative breast cancer (TNBC) cells and has been proposed as a target for cancer drug discovery. Two hit compounds from a medium throughput screen, displayed encouraging inhibition of SOCE in MDA-MB-231 cells, as measured by a Fluorescence Imaging Plate Reader (FLIPR) Ca2+ assay. Following NMR spectroscopic analysis of these hits and reassignment of their structures as 5-hydroxy-5-trifluoromethylpyrazolines, a series of analogues was prepared via thermal condensation reactions between substituted acylhydrazones and trifluoromethyl 1,3-dicarbonyl arenes. Structure-activity relationship (SAR) studies showed that small lipophilic substituents at the 2- and 3-positions of the RHS and 2-, 3- and 4-postions of the LHS terminal benzene rings improved activity, resulting in a novel class of potent and selective inhibitors of SOCE.

Targeting DNA with anti-tumor activity of the naphthalene imide structure biodegradable derivatives, pharmaceutical composition and its preparation method and application

The invention discloses targeted DNA (deoxyribonucleic acid) naphthyldiimide-structure-containing celecoxib derivatives with antitumor activity, of which the structure is disclosed as Formula (I), wherein R is hydrogen, alkyl group or alkoxy group. The invention also discloses a preparation method of the derivatives and application of the derivatives in preparing drugs for resisting mammary cancer, cervical carcinoma and lung adenocarcinoma. The celecoxib structure is modified, and the naphthyldiimide group is used instead of sulfaphenyl group in the celecoxib, thereby designing and synthesizing a series of celecoxib derivatives containing the naphthyldiimide structure unit. The synthesized compounds 5a-5t have certain inhibiting actions on human mammary cancer cells, Hela cells and human lung adenocarcinoma cells. Part of the compounds have excellent antitumor activity, wherein the compounds 5o and 5h have very high selectivity for Hela cells, and the compound 5i has high selectivity for MCF-7 cells. The IC50 value is greatly lower than that of amonafide and higher than that of cis-platinum and celecoxib.

Synthesis, fungicidal activity and mode of action of 4-phenyl-6-trifluoromethyl-2-aminopyrimidines against Botrytis cinerea

Anilinopyrimidines are the main chemical agents for management of Botrytis cinerea. However, the drug resistance in fungi against this kind of compounds is very serious. To explore new potential fungicides against B. cinerea, a series of 4-phenyl-6-trifluoromethyl-2-amino-pyrimidine compounds (compounds III-1 to III-22) were synthesized, and their structures were confirmed by 1H-NMR, IR and MS. Most of these compounds possessed excellent fungicidal activity. The compounds III-3 and III-13 showed higher fungicidal activity than the positive control pyrimethanil on fructose gelatin agar (FGA), and compound III-3 on potato dextrose agar (PDA) indicated high activity compared to the positive control cyprodinil. In vivo greenhouse results indicated that the activity of compounds III-3, III-8, and III-11 was significantly higher than that of the fungicide pyrimethanil. Scanning electron micrography (SEM) and transmission electron micrography (TEM) were applied to illustrate the mechanism of title compounds against B. cinerea. The title compounds, especially those containing a fluorine atom at the ortho-position on the benzene ring, could maintain the antifungal activity against B. cinerea, but their mechanism of action is different from that of cyprodinil. The present study lays a good foundation for us to find more efficient reagents against B. cinerea.

1,5-Diketones Synthesis via Three-Component Cascade Reaction

A mild and efficient cascade synthesis of 1,5-diketones from readily available N,N-dicyclohexylmethylamine, 1,3-dicarbonyl compounds, and trifluoromethyl β-diketones has been developed. This cascade reaction occurs via an oxidation/Mannich reaction/Cope elimination/Michael addition/retro-Claisen reaction sequence, and provides multiple C-C bond formations in one pot. In addition, exquisite chemoselectivity is achieved in the reaction between 1,3-dicarbonyl compounds and trifluoromethyl β-diketones.

Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors

Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50 = 3.3 μM, SI >30.3, 12b, EC50 = 3.5 μM, SI >28.6, 10l, EC50 = 3.9 μM, SI >25.6, 12o, EC 50 = 4.5 μM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents.

Novel Bicyclic Pyridinones

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer

The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [11C]4a-c and [11C]8a-d, were prepared by O-[11C] methylation of their corresponding precursors using [11C]CH3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 52 ± 2% (n = 5) and 57 ± 3% (n = 5) radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5). The IC50 values to block COX-2 for known compounds celecoxib (4d), 4a and 4c were 40, 290 and 8 nM, respectively, and preliminary findings from in vitro biological assay indicated that the synthesized new compounds 4b and 8a-d display similar strong inhibitory effectiveness in the MDA-MB-435 human cancer cell line in comparison with the parent compound 4d. These results encourage further in vivo evaluation of carbon-11-labeled celecoxib derivatives as new potential PET radiotracers for imaging of COX-2 expression in cancer.

GLUCOKINASE ACTIVATORS

Compounds, pharmaceutical compositions, kits and methods are provided for use with glucokinase that comprise a compound selected from the group consisting of: wherein the variables are as defined herein.

Keto-enol and enol-enol tautomerism in trifluoromethyl-β-diketones

The keto-enol (K?E) and enol-enol (E?E) equilibria of a variety of trifluoromethyl-β-diketones were investigated using 1H, 13C, 19F NMR spectroscopy, infrared spectroscopy and ultraviolet-visible spectrophotometry in nonpolar solvents. In general, NMR, IR and UV spectral evidence indicates that trifluoromethyl-β-diketones exist as mixtures of two chelated cis-enol forms in nonpolar media. Infrared spectroscopy and ultraviolet spectrophotometry show the E?E equilibrium lies in the direction of the enol form which maximizes conjugation in most cases. Exceptions are noted and discussed.

Polar substitutions in the benzenesulfonamide ring of celecoxib afford a potent 1,5-diarylpyrazole class of COX-2 inhibitors

Several chemical modifications in the N1-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro.