83141-10-0

Usage

Chemical Properties

Light yellow solid

InChI:InChI=1/C7H3F2NO4/c8-3-1-2-4(10(13)14)6(9)5(3)7(11)12/h1-2H,(H,11,12)/p-1

Upstream product

• 385-00-2 2,6-difluorobenzoic acid 
• 1309431-02-4 benzyl 2,6-difluoro-3-nitrobenzoate 
• 446-35-5 2,4-Difluoronitrobenzene 
• 143879-77-0 2,6-difluoro-3-nitrobenzonitrile 

Downstream Products

• 206884-26-6 2,6-difluoro-3-nitrobenzyl alcohol 
• 260552-98-5 2,6-difluoro-3-nitrobenzoic acid chloride 
• 137332-55-9 (+)-(S)-4,5,6,7-Tetrahydro-8-fluoro-5-methyl-6-(3-methyl-2-butenyl)imidazo<4,5,1-jk><1,4>benzodiazepine-2(1H)-thione 
• 83141-11-1 2,6-difluoro-3-aminobenzoic acid 
• 1103234-46-3 N-(6-acetylamino-3-pyridyl)-2,6-difluoro-3-nitrobenzamide 
• 1103234-56-5 2,6-difluoro-3-(propane-1-sulfonylamino)benzoic acid 
• 1103234-57-6 N-(3-amino-2,4-difluorophenyl)propane-1-sulfonamide 
• 1186193-95-2 methyl 2,6-difluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate 
• 1186193-96-3 2,6-difluoro-3-(N-(propylsulfonyl)(propylsulfonamido))benzoic acid 
• 1186194-05-7 2,6-difluoro-3-(3-fluoropropylsulfonamido)benzoic acid 
• 1269421-43-3 methyl 2,6-difluoro-3-(N-(phenylsulfonyl)(phenylsulfonamido))benzoate 
• 1269421-44-4 2,6-difluoro-3-(phenylsulfonamido)benzoic acid 
• 1269421-42-2 N-(3-amino-2,4-difluorophenyl)benzenesulfonamide 
• 1269421-46-6 methyl 2,6-difluoro-3-(N-(furan-2-ylsulfonyl)(furan-2-sulfonamido))benzoate 

Relevant academic research and scientific papers

Design and synthesis of novel pyrrolo[2,3-b]pyridine derivatives targeting V600EBRAF

Several pyrrolo[2,3-b]pyridine-based B-RAF inhibitors are well known and some of them are currently FDA approved as anticancer agents. Based on the structure of these FDA approved V600EB-RAF inhibitors, two series of pyrrolo[2,3-b]pyridine scaffold were designed and synthesized in attempt to develop new potent V600EB-RAF inhibitors. The 38 synthesized compounds were biologically evaluated for their V600EB-RAF inhibitory effect at single dose (10 μM). Compounds with high percent inhibition were tested to determine their IC50 over V600EB-RAF. Compounds 34e and 35 showed the highest inhibitory effect with IC50 values of 0.085 μM and 0.080 μM, respectively. Headed for excessive biological evaluation, the synthesized derivatives were tested over sixty diverse human cancer cell lines. Only compound 35 emerged as a potent cytotoxic agent against different panel of human cancer cell lines.

Synthesis of novel 8-nitro-substituted 1,3-benzothiazin-4-ones

New 2,5-bis(azacyclohex-1-yl)-8-nitro-1,3-benzothiazin-4-ones were synthesized from 2,6-difluorobenzoic acid in two preparative stages. The ethoxycarbonylpiperazino derivative surpasses in tuberculostatic activity (MIC 4 μg ml?1) its 5-fluoro-8-H-counterpart. The first representative of 5-fluoro-8-nitro-1,3-benzothiazin-4-ones was obtained through the condensation of 2,6-difluoro-3-nitrobenzoyl isothiocyanate and N-methylindole.

Denitrified purine compound and pharmaceutical composition, preparation method and application thereof

The invention relates to denitrified purine compound which has a structure as a following general formula 1, a preparation method of the denitrified purine compound, a pharmaceutical composition containing the denitrified compound and application of the denitrified compound. The compound has selective B-Raf V600E mutation cancer cell inhibition activity, so that the denitrified purine compound disclosed by the invention and the pharmaceutical composition of the denitrified purine compound can be applied to preparing medicine for treating tumor or cancer.

PYRIDINE DERIVATIVE INHIBITING RAF KINASE AND VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR, METHOD FOR PREPARING SAME, PHARMACEUTICAL COMPOSITION CONTAINING SAME, AND USE THEREOF

The present invention provides a novel pyridine derivative, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient. The pyridine derivative according to the present invention inhibits Raf kinase (B-Raf, Raf-1, or B-RafV600E) and a vascular endothelial growth factor receptor (VEGFR2) involved in angiogenesis, and thus, can be favorably used for the prevention or treatment of melanoma, colorectal cancer, prostate cancer, thyroid cancer, lung cancer, pancreatic cancer, ovarian cancer, or the like, which is induced by RAS mutation.

Docking-based structural splicing and reassembly strategy to develop novel deazapurine derivatives as potent B-Raf V600E inhibitors

The mutation of B-Raf V600E is widespread in a variety of human cancers. Its inhibitors vemurafenib and dabrafenib have been launched as drugs for treating unresectable melanoma, demonstrating that B-Raf V600E is an ideal drug target. This study focused on developing novel B-Raf V600E inhibitors as drug leads against various cancers with B-Raf V600E mutation. Using molecular modeling approaches, 200 blockbuster drugs were spliced to generate 283 fragments followed by molecular docking to identify potent fragments. Molecular structures of potential inhibitors of B-Raf V600E were then obtained by fragment reassembly followed by docking to predict the bioactivity of the reassembled molecules. The structures with high predicted bioactivity were synthesized, followed by in vitro study to identify potent B-Raf V600E inhibitors. A highly potent fragment binding to the hinge area of B-Raf V600E was identified via a docking-based structural splicing approach. Using the fragment, 14 novel structures were designed by structural reassembly, two of which were predicted to be as strong as marketed B-Raf V600E inhibitors. Biological evaluation revealed that compound 1m is a potent B-Raf V600E inhibitor with an IC 50 value of 0.05 μmol/L, which was lower than that of vemurafenib (0.13 μmol/L). Moreover, the selectivity of 1m against B-Raf WT was enhanced compared with vemurafenib. In addition, 1m exhibits desirable solubility, bioavailability and metabolic stability in in vitro assays. Thus, a highly potent and selective B-Raf V600E inhibitor was designed via a docking-based structural splicing and reassembly strategy and was validated by medicinal synthesis and biological evaluation.

Discovery of a highly specific and potent pan-RAF inhibitor

We describe the structure-based design and synthesis of N-(2,6-difluorophenyl)-3-(9H-purin-6-yl)pyridine-2-amine derivatives as a selective pan-RAF kinase inhibitor. The synthesized compounds showed highly potent and specific inhibition of the BRAFV600E mutant cell line. Among them, N-(3-((3-(9H-purin-6-yl) pyridine-2-yl)amino)-2,4-difluorophenyl)furan-3-sulfonamide (4b) exhibited the most potent inhibitory activities against protein kinase enzymes BRAFV600E, BRAFWT, and CRAF (IC50 of 2, 2, and 1 nM, respectively) and a mutant cell line bearing a BRAFV600E mutation, A375P (GI50 of 7 nM).

NOVEL PURINYLPYRIDINYLAMINO-2,4-DIFLUOROPHENYL SULFONAMIDE DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION WITH INHIBITORY ACTIVITY AGAINST RAF KINASE, CONTAINING SAME AS ACTIVE INGREDIENT

A novel purinylpyridinylamino-2,4-difluorophenyl sulfonamide derivative, a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutical composition with an inhibitory activity against Raf kinase, containing the same as an active ingredient are provided. The purinylpyridinylamino-2,4-difluorophenyl sulfonamide derivative of the present invention effectively regulates the activity of B-Raf kinase, and thus may be useful for preventing or treating cancers induced by the over-activation of Raf kinase, especially various melanoma, colorectal cancer, prostate cancer, thyroid cancer, ovarian cancer and the like.

A facile approach to the synthesis of 3-(6-Chloro-thiazolo[5,4-b]pyridin-2- ylmethoxy)-2,6-difluoro-benzamide (PC190723)

Practical synthesis of PC 190723, a bacterial cell division protein Ftsz inhibitor, has been achieved in a high overall yield of 45% in six steps from commercially available starting materials. Georg Thieme Verlag Stuttgart · New York.

COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR

Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.

INHIBITORS OF STEAROYL-COA DESATURASE

Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity.