147030-72-6

Upstream product

• 25054-53-9 3,4-(methylenedioxy)benzoyl chloride 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 94-53-1 Piperonylic acid 
• 530-62-1 1,1'-carbonyldiimidazole 
• 1117-97-1 N,0-dimethylhydroxylamine 
• 2635-13-4 1,2-(methylenedioxy)-4-bromobenzene 

Downstream Products

• 437552-71-1 1-benzo[1,3]dioxol-5-yl-2,2-difluoro-ethanone 
• 30418-53-2 1-(benzo[d][1,3]dioxol-5-yl)prop-2-en-1-one 
• 126266-77-1 3,5-methylenedioxy-α-phenylacetophenone 
• 3162-29-6 1-(benzo[d][1,3]dioxol-6-yl)ethanone 
• 40288-65-1 1-(benzo[1,3]dioxol-5-yl)-2-bromoethanone 
• 27738-46-1 3,4-(methylenedioxy)mandelic acid 
• 356560-89-9 1-(benzo[1,3]dioxol-5-yl)-2-(6-methylpyridin-2-yl)ethanone 
• 477-51-0 (5S,5aS,8aR)-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3′,4’:6,7]naphtho[2,3-d][1,3]-dioxol-6(5aH)-one 
• 135755-26-9 (+/-)-dehydrodeoxypodophyllotoxin 
• 477-51-0 rac-(7'β,8α,8'percentb)-3',4',5'-trimethoxy-4,5-methylenedioxy-2,7'-cyclolignan-9',9-olide 
• 98819-09-1 1β-polygamain 
• 98819-09-1 polygamain 

Relevant academic research and scientific papers

Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide

An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.

An α-Cyclopropanation of Carbonyl Derivatives by Oxidative Umpolung

The reactivity of iodine(III) reagents towards nucleophiles is often associated with umpolung and cationic mechanisms. Herein, we report a general process converting a range of ketone derivatives into α-cyclopropanated ketones by oxidative umpolung. Mechanistic investigation and careful characterization of side products revealed that the reaction follows an unexpected pathway and suggests the intermediacy of non-classical carbocations.

Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-β type 1 receptor inhibitors

Inhibition of transforming growth factor β (TGF-β) type 1 receptor (ALK5) provides a feasible approach for the treatment of fibrotic diseases and malignant tumors. In this study, we designed and synthesized a new series of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives, and evaluated biologically as TGF-β type 1 receptor inhibitors. The most potent compound 15r inhibited the ALK5 enzyme and NIH3T3 cell viability with IC50 values of 44 and 42.5 nM, respectively. Compound 15r also displayed better oral plasma exposure and excellent bioavailability than LY-3200882, and in vivo inhibited 65.7% of the tumor growth in a CT26 xenograft mouse model.

Iron-Catalyzed, Iminyl Radical-Triggered Cascade 1,5-Hydrogen Atom Transfer/(5+2) or (5+1) Annulation: Oxime as a Five-Atom Assembling Unit

By integration of iminyl radical-triggered 1,5-hydrogen atom transfer and (5+2) or (5+1) annulation processes, a series of structurally novel and interesting azepine and spiro-tetrahydropyridine derivatives have been successfully prepared in moderate to good yields. This method utilizes FeCl2 as the catalyst and readily available oximes as five-atom units, while showcasing broad substrate scope and good functional group compatibility. The annulation products can be easily converted into many valuable compounds. Moreover, DFT calculation studies are performed to provide some insights into the possible reaction mechanisms for the (5+2) and (5+1) annulations.

Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents

Microtubule-targeting agents (MTAs) are a class of clinically successful anti-cancer drugs. The emergence of multidrug resistance to MTAs imposes the need for developing new MTAs endowed with diverse mechanistic properties. Benzoxazepines were recently identified as a novel class of MTAs. These anticancer agents were thoroughly characterized for their antitumor activity, although, their exact mechanism of action remained elusive. Combining chemical, biochemical, cellular, bioinformatics and structural efforts we developed improved pyrrolonaphthoxazepines antitumor agents and their mode of action at the molecular level was elucidated. Compound 6j, one of the most potent analogues, was confirmed by X-ray as a colchicine-site MTA. A comprehensive structural investigation was performed for a complete elucidation of the structure-activity relationships. Selected pyrrolonaphthoxazepines were evaluated for their effects on cell cycle, apoptosis and differentiation in a variety of cancer cells, including multidrug resistant cell lines. Our results define compound 6j as a potentially useful optimized hit for the development of effective compounds for treating drug-resistant tumors.

Identification of a series of highly potent activators of the Nurr1 signaling pathway

The nuclear receptor Nurr1 (NR4A2) is critically involved in the development and maintenance of midbrain dopaminergic neurons and is believed to function independently of endogenous activation. The hit identification and SAR studies leading to isoxazolo-pyridinone 7e, a highly potent, brain penetrable activator of the Nurr1 signaling pathway, are described.

Tri-substituted heteroaryls and methods of making and using the same

Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of the general formula (I).

Radical-mediated synthesis of racemic deoxypodophyllotoxin and related lignans

An approach for the synthesis of lignans related to the podophyllotoxin family is reported. The key reaction is a highly diastereoselective iodoacetal cyclization under iodine atom transfer conditions followed by a hornolytic aromatic substitution. The second aromatic ring is introduced at a later stage via addition of aryllithium to an aryl ketone. A novel and very mild method for the deoxygenation of the intermediate tertiary benzylic alcohols is described. Georg Thieme Verlag Stuttgart.

NOVEL TRIAZOLE AND OXAZOLE COMPOUNDS AS TRANSFORMING GROWTH FACTOR (TGF) INHIBITOR

Novel oxazole and thiazole compounds, including derivatives thereof, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use are described. The compounds of the present invention are potent inhibitors of transforming growth factor ("TGF")-β signaling pathway. They are useful in the treatment of various TGF-related disease states including, for example, cancer and fibrotic diseases.

Novel fused heteroaromatic compounds as transforming growth factor (TGF) inhibitors

Novel fused heteroaromatic compounds, including derivatives thereof, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use are described. The compounds of the present invention are potent inhibitors of transforming growth factor (“TGF”)-β signaling pathway. They are useful in the treatment of various TGF-related disease states including, for example, cancer and fibrotic diseases.