79455-63-3

Usage

Chemical Properties

Light yellow liquid

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

Upstream product

• 434-75-3 2-chloro-6-fluorobenzoic acid 

Downstream Products

• 116800-84-1 N-(Bis-methylsulfanyl-methylene)-2-chloro-6-fluoro-benzamide 
• 850083-65-7 N-(6-aminopyridin-2-yl)-2-chloro-6-fluorobenzamide 
• 1364304-91-5 4-[3-(2-chloro-6-fluorobenzoylamino)phenoxy]piperidine-1-carboxylic acid tert-butyl ester 
• 857870-07-6 N-(2-chloro-6-fluorobenzoyl)-4-(6-iodo-1-methyl-2,4-quinazoline-dione-3-yl)-L-phenylalanine methylester 
• 116370-12-8 2-chloro-6-fluoro-N'-(o-chlorophenyl)-benzhydrazide 
• 936481-85-5 C₂₂H₃₀ClFN₂O₃ 
• 1000781-98-5 tert-butyl 4-(6-chloro-2-fluorobenzoyl)-3-(hydroxymethyl)piperazine-1-carboxylate 
• 857870-01-0 N-(2-chloro-6-fluorobenzoyl)-4-(6-dimethylamino-1-methyl-2,4-quinazoline-d ione-3-yl)-L-phenylalanine trifluoroacetate methylester 
• 868373-87-9 methyl 3-(2-chloro-6-fluorophenyl)-3-oxopropionate 
• 66073-54-9 2-chloro-6-fluoro-benzamide 

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.

SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS AS mPGES-1 INHIBITORS

The present invention relates to bicyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (m PGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthama, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases. (I)

Copper-promoted sandmeyer trifluoromethylation reaction

A copper-promoted trifluoromethylation reaction of aromatic amines is described. This transformation proceeds smoothly under mild conditions and exhibits good tolerance of many synthetically relevant functional groups. It provides an alternative approach for the synthesis of trifluoromethylated arenes and heteroarenes. It also constitutes a new example of the Sandmeyer reaction.

Lead optimization of a 4-aminopyridine benzamide scaffold to identify potent, selective, and orally bioavailable TYK2 inhibitors

Herein we report our lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with lead molecule 3. We used structure-based design to discover 2,6-dichloro-4-cyanophenyl and (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved TYK2 potency and JAK1 and JAK2 selectivity relative to 3. Further optimization eventually led to compound 37 that showed good TYK2 enzyme and interleukin-12 (IL-12) cell potency, as well as acceptable cellular JAK1 and JAK2 selectivity and excellent oral exposure in mice. When tested in a mouse IL-12 PK/PD model, compound 37 showed statistically significant knockdown of cytokine interferon-γ (IFNγ), suggesting that selective inhibition of TYK2 kinase activity might be sufficient to block the IL-12 pathway in vivo.

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.

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.

Compounds and method for inhibiting MRP1

The present invention relates to a compound of formula (I), which is useful for inhibiting resistant neoplasms where the resistance is conferred in part or in total by MRP1.