39847-96-6

Upstream product

• 113416-24-3 (Z)-4-(4-Nitro-phenyl)-4-oxo-2-phenylamino-but-2-enoic acid methyl ester 
• 553-90-2 Dimethyl oxalate 
• 100-19-6 (4-nitrophenyl)ethanone 

Downstream Products

• 147670-83-5 (Z)-2-Hydroxy-4-(4-nitro-phenyl)-4-oxo-but-2-enoic acid 
• 1193109-54-4 (2Z,5Z)-3-hydroxy-5-[3,3-dimethyl-6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-ylidene]-1-(4-nitrophenyl)pent-2-ene-1,4-dione 

Relevant academic research and scientific papers

Novel dimeric aryldiketo containing inhibitors of HIV-1 integrase: Effects of the phenyl substituent and the linker orientation

Aryl diketoacids (ADK) and their bioisosteres are among the most promising HIV-1 integrase (IN) inhibitors. Previously, we designed a series of ADK dimers as a new class of IN inhibitors that were hypothesized to target two divalent metal ions on the active site of IN. Herein we present a further structure-activity relationship (SAR) study with respect to the substituent effect of the ADK and the dimerization with conformationally constrained linkers such as piperazine, 4-amino-piperidine, piperidin-4-ol, and trans-cyclohexan-1,4-diamine. The substituents on the phenyl ring as well as the spatial orientation of the two diketo units were observed to play important roles in the IN inhibitory potency. The hydrophobic group was an optimal substitution at the 3-position of the aryl ring. The piperazine and 4-amino-piperidine linkers brought about the most potent analogs among the hydrophobic group or halogen substituted ADK dimers. The docking studies suggested that the bulky hydrophobic substitution at 3-phenyl ring and the linker of 4-amino-piperidine were beneficial for adopting an active conformation to achieve strong interactions with the active site Mg2+ and the key residue E152 within the catalytic core domain. This study is a significant extension of our previous report on the dimeric ADK-containing IN inhibitors, providing a new promising template for further lead optimization.

Study of the Mechanisms of Reactions of 1,3-Dicarbonyl Compounds with Nucleophilic Reagents: X. Kinetics of the Hydrolysis of Methyl 4-Aryl-2-Arylamino-4-Oxobut-2-Enoates

The kinetics of hydrolysis of methyl 4-aryl-2-arylamino-4-oxobut-2-enoates in 50% aqueous dioxane in the presence of acetate and monochloroacetate buffer solutions was studied by spectrophotometry. An analysis of the dependence of the rate of hydrolysis on the concentrations and the composition of the components of the solutions and on the nature of the substituents in the substrate made it possible to propose a mechanism of general acid catalysis of the reaction.