674802-90-5

Upstream product

• 462-06-6 fluorobenzene 
• 934560-46-0 N-[2-(4-fluorobenzoyl)phenyl]-4-methylbenzenesulfonamide 
• 42840-02-8 2-(Toluene-4-sulfonylamino)-benzoyl chloride 
• 118-92-3 anthranilic acid 
• 6311-23-5 2-(toluene-4-sulfonylamino)-benzoic acid 
• 3800-06-4 2-amino-4'-fluorobenzophenone 
• 40913-92-6 4-methylsulfonylbenzoyl chloride 

Relevant academic research and scientific papers

2,3-Diaryl-substituted indole based COX-2 inhibitors as leads for imaging tracer development

A series of 2,3-diaryl-substituted indoles containing a fluorine or methoxy group was synthesized via Fischer indole synthesis, McMurry cyclization, or Bischler-Moehlau reaction to identify potential leads for positron emission tomography (PET) radiotracer development as well as for optical imaging. All 2,3-diaryl-substituted indoles possess autofluorescent properties with an emission maximum in a range of 443-492 nm, which is acceptable for biological studies in vitro and, in part, in vivo. The molecular structure of compounds 3a and 3j was confirmed by X-ray crystal structure analysis. COX inhibitory activity was evaluated by a fluorescence-based and enzyme immunoassay-based assay. Redox activity of all target compounds was also determined. All synthesized 2,3-diaryl-substituted indoles are inhibitors of COX-2 enzyme in the low micromolar range. Compounds 3e, 3f, 3g and 3m displayed a 30-40% inhibition of COX-2 at 0.1 μM concentration while compounds 3f and 3g also exhibited COX-1 inhibitory activity. Various compounds like 3g showed substantial antioxidative potential (RDIENE = 2.85, RHAVA = 1.98), an effect that was most measurable with methoxy-substituted compounds. With respect to PET radiotracer synthesis, OMe-containing compound 3j was selected as a promising candidate for carbon-11 labeling, and F-containing compound 3m as a lead for the development of a fluorine-18 labeled derivative. the Partner Organisations 2014.

Radiosynthesis of a 18F-labeled 2,3-diarylsubstituted indole via McMurry coupling for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo

The radiosynthesis of 3-(4-[18F]fluorophenyl)-2-(4- methylsulfonylphenyl)-1H-indole [18F]-3 as potential PET radiotracer for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo is described. [18F]-3 was prepared by McMurry cyclization of a 18F-labeled intermediate with low valent titanium and zinc via a two-step procedure in a remote controlled synthesizer unit including HPLC purification and solid phase extraction. In this way [18F]-3 was synthesized in 80 min synthesis time in 10% total decay corrected yield from [18F]fluoride in radiochemical purity >98% and a specific activity of 74-91 GBq/μmol (EOS). [18F]-3 was evaluated in vitro using pro-inflammatory stimulated THP-1 and COX-2 expressing tumor cell lines (FaDu, A2058, HT-29), where the radiotracer uptake was shown to be consistent with up regulated COX-2 expression. The stability of [18F]-3 was determined by incubation in rat whole blood and plasma in vitro and by metabolite analysis of arterial blood samples in vivo, showing with 75% of original compound after 60 min an acceptable high metabolic stability. However, no substantial tumor accumulation of [18F]-3 could be observed by dynamic small animal PET studies on HT-29 tumor-bearing mice in vivo. This may be due to the only moderate COX-1/COX-2 selectivity of 3 as demonstrated by both cellular and enzymatic cyclooxygenase inhibition assay in vitro. Nevertheless, the new approach first using McMurry cyclization in 18F-chemistry gives access to 18F-labeled diarylsubstituted heterocycles that hold promise as radiolabeled COX-2 inhibitors.

Sulfonyl-containing 2,3-diarylindole compounds, methods for making same, and methods of use thereof

The present invention relates to sulfonyl-containing 2,3-diarylindole, especially to new compounds of general Formula, to a preparation method for their preparation, to pharmaceutical compositions containing said compound, and to the medical use thereof in the treatment of diseases relating to the inhibition of cyclooxygenase-2 (COX-2).

Synthesis and biological evaluation of substituted 2-sulfonyl-phenyl-3-phenyl-indoles: A new series of selective COX-2 inhibitors

A new series of substituted 2-sulfonyphenyl-3-phenyl-indole derivatives were synthesized and evaluated for their ability to inhibit COX-2 and COX-1enzymes. Most of the compounds synthesized were found to be highly potent and selective inhibitors of COX-2. This work led to the discovery of 2-aminosulfonylphenyl-3-phenyl-indole 5a which possesses higher activity and selectivity for COX-2 than Celecoxib both in vitro and in vivo.