874804-29-2

Upstream product

• 372-39-4 3,5-difluoroaniline 
• 79-04-9 chloroacetyl chloride 

Downstream Products

• 1044504-90-6 N-(3,5-difluorophenyl)-2-(3-{4-[(methyloxy)methyl]phenyl}-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)acetamide 
• 1242606-95-6 C₂₇H₂₅F₂N₅O 

Relevant academic research and scientific papers

Synthesis and Biological Evaluation of Dithiobisacetamides as Novel Urease Inhibitors

Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 μM. Of note, 2,2′-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2′-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2′-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 μM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.

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.

Synthesis and antitumor activities of novel 1,4-substituted phthalazine derivatives

A series of 1,4-substituted phthalazine derivatives were designed and synthesized. All the prepared compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. Among them, compounds 7a-7h showed excellent selectivity for MDA-MB-231 cell line with IC50 values from 1nmol/L to 0.92μmol/L. A preliminary SAR study of these derivatives was performed.

GLYT1 TRANSPORTER INHIBITORS AND USES THEREOF IN TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS

Compounds of Formula (I) or a salt thereof are provided: wherein R1, R2, R3, R4, R5, R6, R15, R7, R8 and m are as defined in the description. Uses of the co

BENZENESULFONAMIDE COMPOUNDS AND THEIR USE AS BLOCKERS OF CALCIUM CHANNELS

The invention relates to piperidinyl and hexahydroazepinyl compounds of Formula (I): and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein R1-R3, Z and q are defined as set forth in the specification. The inve

Bicyclic pyrazole compounds as antibacterial agents

Antibacterial compounds, compositions containing them, and methods of use for the inhibition of bacterial activity and the treatment, prevention or inhibition of bacterial infection.