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Upstream product

• 104960-50-1 4-(trifluoromethyl)-1,2-dihydro-6-(thiophen-2-yl)-2-thioxopyridine-3-carbonitrile 
• 587-65-5 N-chloroacetyl-aniline 
• 62-53-3 aniline 
• 104960-50-1 C₁₁H₅F₃N₂S₂ 
• 326-91-0 1,1,1-trifluoro-4-(2-thienyl)butane-2,4-dione 
• 299198-18-8 2-(3-cyano-6-thiophen-2-yl-4-trifluoromethyl-pyridin-2-ylsulfanyl)-N-phenyl-acetamide 

Relevant academic research and scientific papers

A structure-activity relationship study of Forkhead Domain Inhibitors (FDI): The importance of halogen binding interactions

The Forkhead boX M1 (FOXM1) protein is an essential transcription factor required for the normal activation of human cell cycle. However, increasing evidence supports a correlation between FOXM1 overexpression and the onset of several types of cancer. Based on a previously reported molecular modeling and molecular dynamics simulations (MD) study, we hypothesized the role of an essential halogen-bonding interaction between the 4-fluorophenyl group in the forkhead domain inhibitor-6 (FDI-6) and an Arg297 residue inside the FOXM1-DNA binding domain (DBD). To prove the importance of this binding interaction, we synthesized and screened ten FDI-6 derivatives possessing different groups at the 4-fluorophenyl position of the lead molecule. Briefly, we found that derivatives possessing a 4-chlorophenyl, 4-bromophenyl, or a 4-iodophenyl group, were equipotent to the original 4-fluorophenyl moiety present in FDI-6, whereas derivatives without this 4-halogen moiety were inactive. We also observed that positional isomers in which the halogen was relocated to positions 2- or 3- on the phenyl group were significantly less active. These results provide evidence to support the essential role of a 4-halophenyl bonding interaction, with the Arg297 residue in the FOXM1-DBD, to exert inhibition of transcriptional activity.

Fluorine-containing heterocycles: Synthesis and some reactions of new 3-amino-2-functionalized-6-(2′-thienyl)-4-trifluoromethylthieno [2,3-b]pyridines

3-Cyano-6-(2′-thienyl)-4-trifluoromethylpyridine-2(1H)-thione (2) was prepared and reacted with chloroacetone or phenacyl bromide to yield the 2-acetyl or benzoyl-3-amino-6-(2′-thienyl)-4-trifluoromethylthieno[2,3-b]pyridines (3a, b). In contrast, the reaction of 2 with chloroacetamide or its N-aryl derivatives gave the corresponding 2-carbamoylmethyl thiopyridines 4a-c. Upon treatment of these educts with K2CO3 or C2H5ONa in ethanol, they underwent intramolecular Thorpe-Ziegler cyclization to afford 3-amino-2-carbamoyl-6-(2′-thienyl)-4-trifluoromethyl-thieno[2,3-b]pyrid ine (5a) and its N-aryl analogs 5b, c. Compounds 5a-c underwent some reactions to yield new pyrido[3',2':4,5]thieno[3,2-d]pyrimidines and pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3] triazines.