895572-24-4

Upstream product

• 327056-73-5 3-fluoro-5-chlorobenzonitrile 
• 16766-30-6 4-Chloroguaiacol 
• 3743-23-5 5-chloro-2-methoxyphenol 
• 895572-18-6 3-chloro-5-(5-chloro-2-methoxyphenoxy)benzonitrile 

Downstream Products

• 1068603-73-5 C₁₈H₁₄Cl₂N₄O₄S 
• 1351862-45-7 3-chloro-5-(5-chloro-2-(2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)phenoxy)benzonitrile 
• 1351861-78-3 3-(2-(2-bromoethoxy)-5-chlorophenoxy)-5-chlorobenzonitrile 
• 1071569-17-9 C₂₅H₂₀Cl₂N₄O₄ 

Relevant academic research and scientific papers

Diaryl ethers with carboxymethoxyphenacyl motif as potent HIV-1 reverse transcriptase inhibitors with improved solubility

In search of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) with improved solubility, two series of novel diaryl ethers with phenacyl moiety were designed and evaluated for their HIV-1 reverse transcriptase inhibition potentials. All compounds exhibited good to excellent results with IC50 at low micromolar to submicromolar concentrations. Two most active compounds (7e and 7 g) exhibit inhibitory potency comparable or even better than that of nevirapine and rilpivirine. Furthermore, SupT1 and CD4+ cell infectivity assays for the most promising (7e) have confirmed its strong antiviral potential while docking studies indicate a novel binding interactions responsible for high activity.

Computationally-guided optimization of a docking hit to yield catechol diethers as potent anti-HIV agents

A 5-μM docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (FEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity. (Figure presented)

CHEMICAL COMPOUNDS

This invention relates to biaryl ether derivatives of formula (I), wherein R1, R3, R4, X, W, Y and m are defined in the description, and to compositions containing them and the uses of such derivatives. The compounds of th