84267-54-9

Upstream product

• 831-82-3 4-Phenoxyphenol 
• 106-89-8 epichlorohydrin 
• 25345-76-0 1-phenoxy-4-allyloxybenzene 

Downstream Products

• 57650-78-9 4-phenoxyphenyl (R,S)-2-hydroxypropyl ether 
• 63837-30-9 2RS-2,3-dihydroxy-1-(4-phenoxyphenoxy)propane 

Relevant academic research and scientific papers

Design and Evaluation of New Quinazolin-4(3 H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa

P. aeruginosa (PA) continues to pose a threat to global public health due to its high levels of antimicrobial resistance (AMR). The ongoing AMR crisis has led to an alarming shortage of effective treatments for resistant microbes, and hence there is a pressing demand for the development of novel antimicrobial interventions. The potential use of antivirulence therapeutics to tackle bacterial infections has attracted considerable attention over the past decades as they hamper the pathogenicity of target microbes with reduced selective pressure, minimizing the emergence of resistance. One such approach is to interfere with the PA pqs quorum sensing system which upon the interaction of PqsR, a Lys-R type transcriptional regulator, with its cognate signal molecules 4-hydroxy-2-heptylquinoline (HHQ) and 2-heptyl-3-hydroxy-4-quinolone (PQS), governs multiple virulence traits and host-microbe interactions. In this study, we report the hit identification and optimization of PqsR antagonists using virtual screening coupled with whole cell assay validation. The optimized hit compound 61 ((R)-2-(4-(3-(6-chloro-4-oxoquinazolin-3(4H)-yl)-2-hydroxypropoxy)phenyl)acetonitrile) was found to inhibit the expression of the PA PpqsA promoter controlled by PqsR with an IC50 of 1 μM. Using isothermal titration calorimetry, a Kd of 10 nM for the PqsR ligand binding domain (PqsRLBD) was determined for 61. Furthermore, the crystal structure of 61 with PqsRLBD was attained with a resolution of 2.65 ?. Compound 61 significantly reduced levels of pyocyanin, PQS, and HHQ in PAO1-L, PA14 lab strains and PAK6085 clinical isolate. Furthermore, this compound potentiated the effect of ciprofloxacin in early stages of biofilm treatment and in Galleria mellonella infected with PA. Altogether, this data shows 61 as a potent PqsR inhibitor with potential for hit to lead optimization toward the identification of a PA QS inhibitor which can be advanced into preclinical development.

Design and synthesis of a novel and potent series of inhibitors of cytosolic phospholipase A2 based on a 1,3-disubstituted propan-2-one skeleton

Using knowledge of the substrate specificity of cPLA2 (phospholipases A2), a novel series of inhibitors of this enzyme were designed based upon a three point model of inhibitor binding to the enzyme active site comprising a lipophilic anchor, an electrophilic serine "trap", and an acidic binding moiety. The resulting 1,3-diheteroatom-substituted propan-2-ones were evaluated as inhibitors of cPLA2 in both aggregated bilayer and soluble substrate assays. Systematic variation of the lipophilic, electrophilic, and acidic groups revealed a well-defined structure-activity relationship against the enzyme. Optimization of each group led to compound 22 (AR-C70484XX), which contains a decyloxy lipophilic side chain, a 1,3-diaryloxypropan-2-one moiety as a unique serine trap, and a benzoic acid as the acidic binding group. AR-C70484XX was found to be among the most potent in vitro inhibitors of cPLA2 described to date being more than 20-fold more active against the isolated enzyme (IC50 = 0.03 μM) than the standard cPLA2 inhibitor, arachidonyl trifluoromethyl ketone (AACOCF3), and also greater than 10-fold more active than AACOCF3 against the cellular production of arachidonic acid by HL60 cells (IC50 = 2.8 μM).

Design, synthesis, and anti-Trypanosoma cruzi evaluation of a new class of cell-growth inhibitors structurally related to Fenoxycarb

Several compounds, structurally related to the insect-growth regulator Fenoxycarb (1), were designed and synthesized. These compounds were tested as growth inhibitors of Trypanosoma cruzi cells (epimastigotes). Compounds 6, 16, 18, and 22 were very active against T. cruzi making them promising good candidates either for blood-bank sterilization or Chagas'-disease surveillance, while compounds 11, 12, 13, and 19 showed a moderate degree of activity.