21900-54-9

Usage

Chemical Properties

Clear pale yellow to yellow liquid

InChI:InChI=1/C7H3Cl2FO/c8-6-3-4(10)1-2-5(6)7(9)11/h1-3H

Upstream product

• 2252-51-9 2-choro-4-fluorobenzoic acid 
• 79-37-8 oxalyl dichloride 

Downstream Products

• 201686-69-3 6-[bis-(2-chloro-4-fluoro-benzoyl)-amino]-nicotinic acid ethyl ester 
• 252917-77-4 3-(2-chloro-4-fluorobenzamido)pyridine 
• 252917-78-5 3-(2-chloro-4-fluorobenzamido)quinoline 
• 69943-47-1 (2-chloro-4-fluorophenyl)(phenyl)methanone 
• 220603-04-3 (2-chloro-4-fluorophenyl)-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone 
• 346608-00-2 2-chloro-4-fluorobenzoic acid 2-pyridinylmethyl ester 
• 220602-55-1 [2-chloro-4-(3-methyl-1H-pyrazol-1-yl)-phenyl]-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone 
• 220602-58-4 [2-Chloro-4-(5-methyl-1H-pyrazol-1-yl)-phenyl]-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone 
• 875414-12-3 [2-chloro-4-(5-trifluoromethyl-pyrazol-1-yl)-phenyl]-(5,11-dihydro-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)-methanone 
• 220602-88-0 {2-Chloro-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl}-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone 
• 875479-20-2 2-chloro-4-pyrrolidinobenzophenone 
• 875479-24-6 1-(2-chloro-4-pyrrolidinophenyl)-1-phenylprop-2-yn-1-ol 

Relevant academic research and scientific papers

Discovery of [1,2,4]triazolo[4,3-a]pyridines as potent Smoothened inhibitors targeting the Hedgehog pathway with improved antitumor activity in vivo

Triple-negative breast cancer (TNBC), a subset of breast cancers, have poorer survival than other breast cancer types. Recent studies have demonstrated that the abnormal Hedgehog (Hh) pathway is activated in TNBC and that these treatment-resistant cancers are sensitive to inhibition of the Hh pathway. Smoothened (Smo) protein is a vital constituent in Hh signaling and an attractive drug target. Vismodegib (VIS) is one of the most widely studied Smo inhibitors. But the clinical application of Smo inhibitors is limited to adult patients with BCC and AML, with many side effects. Therefore, it's necessary to develop novel Smo inhibitor with better profiles. Twenty [1,2,4]triazolo[4,3-a]pyridines were designed, synthesized and screened as Smo inhibitors. Four of these novel compounds showed directly bound to Smo protein with stronger binding affinity than VIS. The new compounds showed broad anti-proliferative activity against cancer cell lines in vitro, especially triple-negative breast cancer cells. Mechanistic studies demonstrated that TPB15 markedly induced cell cycle arrest and apoptosis in MDA-MB-468 cells. TPB15 blocked Smo translocation into the cilia and reduced Smo protein and mRNA expression. Furthermore, the expression of the downstream regulatory factor glioma-associated oncogene 1 (Gli1) was significantly inhibited. Finally, TPB15 demonstrated greater anti-tumor activity in our animal models than VIS with lower toxicity. Hence, these results support further optimization of this novel scaffold to develop improved Smo antagonists.

ARYL AND HETEROARYL ETHER DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE

Substituted aryl and heteroaryl ether compounds of the Formula (I) and pharmaceutically acceptable salts thereof, wherein X, R 1, R 2, R 3, L, R 4, L 1, Q, and R 5 are as defined herein. These compounds and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

Studies on phenothiazines: New microtubule-interacting compounds with phenothiazine A-ring as potent antineoplastic agents

New phenothiazine derivatives 6-20 have been designed, synthesized and evaluated in vitro for their ability to inhibit tubulin polymerization and antiproliferative activity against 60 cancer cell lines, including several multi-drug resistant (MDR) tumor cell lines. The phenothiazine unit may successfully replace the classical 3,4,5-trimethoxyphenyle A ring of parent combretastatin A-4 or phenstatin, confirming previous studies. The most promising structural modulations have been realized on the B ring, the 2′-fluoro-4′-methoxy substitution in compound 6 and the 2′-trifluoromethyl-4′-methoxy substitution in compound 7 providing the best antitubulin and antitumor activity in the current study. Compounds 6-8 and 16 exhibited more important cell growth inhibition than parent phenstatin 2 on human colon Duke's type D, colorectal adenocarcinoma COLO 205 and on human kidney adenocarcinoma A498 cell lines. 10-Methylphenothiazine derivatives 19 and 20 did not show biological activity but exerted bright fluorescence and solvatochromism effects. These molecules deserve further chemical efforts in order to provide valuable tools for biophysical studies.

P2X7 MODULATORS

The present invention is directed to compounds of Formulas (I, IIa and IIb): The invention also relates to pharmaceutical compositions comprising compounds of Formulas (I, IIa and IIb). Methods of making and using the compounds of Formulas (I, IIa and IIb) are also within the scope of the invention.

ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS

Formula (I), and salts thereof, wherein R1, RA2, RA3 and RA4, are defined herein, which have properties for positive allosteric modulation of mGluR-4 receptor sites. Also described are pharmaceutical formulations comprising the compounds of Formula (I) or their salts, and methods of treating Parkinson's disease and related disorders using the same.

ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS

Disclosed are compounds of Formula (I), and salts thereof, wherein R1, RA2, RA3 and RA4, are defined herein, which have properties for positive allosteric modulation of mGluR-4 receptor sites. Also described are pharmaceutical formulations comprising the compounds of Formula (I) or their salts, and methods of treating Parkinson's disease and related disorders using the same.

Palladium-catalyzed direct ortho -alkynylation of aromatic carboxylic acid derivatives

The palladium-catalyzed direct alkynylation of C-H bonds in aromatic carboxylic acid derivatives is described. The use of 8-aminoquinoline as a directing group facilitates the alkynylation of an electronically diverse range of C(sp2)-H bonds.

Synthesis and anti-cancer, anti-metastatic evaluation of some new fluorinated isocoumarins and 3,4-dihydroisocoumarins

Synthesis of some fluorinated isocoumarins and 3,4-dihydroisocoumarins is reported. Structures of the synthesized compounds were confirmed by spectral and elemental analysis. All the synthesized compounds were evaluated for their antimetastatic activity and anti-cancer activity against breast cell line (MCF-7). Among all the tested compounds 3h [3-(3′,4′-difluorophenyl) isocoumarin] has shown excellent antimetastatic activity, however the growth inhibitory response of the tested compounds [3a-h, 4a-h, 5e-h, 6a-h and 7a, c, d] for MCF-7 human breast carcinoma cell line was moderate at higher concentrations (100-400 μM) and negligible at lower concentrations.

A highly efficient copper-catalyzed method for the synthesis of 2-hydroxybenzamides in water

An efficient copper-catalyzed synthetic method for the preparation of 2-hydroxybenzamides is described for the first time from 2-chlorobenzamide substrates using copper iodide/1,10-phenanthroline and a base, potassium hydroxide, in neat water. By using this reaction, a series of 2-hydroxybenzamides with functional groups such as fluoro, chloro, iodo, methoxy, amide, and alcohol have been obtained in 33-96% yield. Other aromatic 2-chloroarylamides such as naphthalene, pyridine, and thiophene are found to be equally compatible to the reaction. It is proposed that the reaction proceed via formation of copper-amide complex, which may facilitate the hydroxylation in water. Overall, the first report on copper-catalyzed hydroxylation reaction in water and first catalytic route for the synthesis of 2-hydroxybenzamides is presented. Simple purification procedure and convenience of employing low-cost reagents in neat water make this method practical and economical for the synthesis of 2-hydroxybenzamides. Georg Thieme Verlag Stuttgart · New York.

Synthesis of (2-chlorophenyl)(phenyl)methanones and 2-(2-chlorophenyl)-1- phenylethanones by Friedel-Crafts acylation of 2-chlorobenzoic acids and 2-(2-chlorophenyl)acetic acids using microwave heating

Several 2-(2-chlorophenyl)-1-phenylethanones and (2-chlorophenyl)(phenyl) methanones were prepared by the Friedel-Crafts acylation reaction of 2-(2-chlorophenyl) acetic acids and 2-chlorocarboxylic acids, respectively, in the presence of cyanuric chloride, pyridine, and AlCl3 or FeCl 3 using microwave heating. The yields of the ketones were significantly higher than those obtained using conventional heating. In addition, similar reactions carried out with the less inexpensive and less toxic FeCl3 gave titled ketones in comparable yields. Interestingly, the FeCl3 catalyzed reactions gave pure ketones (no chromatographic purification required), whereas the AlCl3 catalyzed reaction gave impure product that required chromatographic purification.