85593-77-7

Upstream product

• 89-86-1 4-hydroxysalicylic acid 
• 100-44-7 benzyl chloride 
• 100-39-0 benzyl bromide 
• 85593-76-6 methyl 2,4-bis(benzyloxy)benzoate 
• 2150-47-2 methyl 2,4-dihydroxybenzoate 
• 95-01-2 2,4-Dihydroxybenzaldehyde 
• 13246-46-3 2,4-dibenzyloxybenzaldehyde 

Downstream Products

• 85593-78-8 2-formyl-4,5-methylenedioxyphenyl 2',4'-dibenzyloxybenzoate 
• 170281-93-3 methyl N-(2,4-dibenzyloxybenzoyl)glycinate 
• 1026882-22-3 3-(2,4-Bis-benzyloxy-benzoylamino)-propionic acid methyl ester 
• 5448-45-3 4-(benzyloxy)-2-hydroxybenzoic acid 
• 125718-81-2 (5-{(S)-2-[2-(2,4-Bis-benzyloxy-phenyl)-acetylamino]-3-carbamoyl-propionylamino}-pentyl)-carbamic acid tert-butyl ester 
• 113978-98-6 dibenzyl-2,4-dihydroxyphenylacetic acid N-hydroxysuccinimide ester 
• 113954-15-7 (S)-N¹-(5-Amino-pentyl)-2-[2-(2,4-bis-benzyloxy-phenyl)-acetylamino]-succinamide 
• 121903-72-8 1-(2,4-Bis-benzyloxy-phenyl)-2-diazo-ethanone 
• 105029-41-2 Argiotoxin 636 
• 174007-70-6 C₇₅H₈₈N₁₀O₁₄ 
• 174007-67-1 (S)-2-[2-(2,4-Bis-benzyloxy-phenyl)-acetylamino]-N¹-(5-hydroxy-pentyl)-succinamide 
• 172992-23-3 (S)-2-[2-(2,4-Bis-benzyloxy-phenyl)-acetylamino]-N¹-(5-oxo-pentyl)-succinamide 
• 1331965-86-6 N-(2,4-bis(benzyloxy)phenyl)-6-iodobenzo[d][1,3]dioxole-5-carboxamide 
• 1331965-90-2 C₃₄H₃₆INO₆Si 

Relevant academic research and scientific papers

Inhibition of Plasmodium falciparum Lysyl-tRNA Synthetase via a Piperidine-Ring Scaffold Inspired Cladosporin Analogues

Plasmodium falciparum lysyl-tRNA synthetase (PfKRS) represents a promising therapeutic anti-malarial target. Cladosporin was identified as a selective and potent PfKRS inhibitor but lacks metabolic stability. Here, we report chemical synthesis, biological evaluation and structural characterization of analogues where the tetrahydropyran (THP) frame of cladosporin is replaced with the piperidine ring bearing functional group variations. Thermal binding, enzymatic, kinetic and parasitic assays complemented with X-ray crystallography reveal compounds that are moderate in potency. Co-crystals of Cla?B and Cla?C with PfKRS reveal key atomic configurations that allow drug binding to and inhibition of the enzyme. Collectively these piperidine ring scaffold inhibitors lay a framework for further structural editing and functional modifications of the cladosporin scaffold to obtain a potent lead.

Biological Characterization, Mechanistic Investigation and Structure-Activity Relationships of Chemically Stable TLR2 Antagonists

Toll-like receptors (TLRs) build the first barrier in the innate immune response and therefore represent promising targets for the modulation of inflammatory processes. Recently, the pyrogallol-containing TLR2 antagonists CU-CPT22 and MMG-11 were reported; however, their 1,2,3-triphenol motif renders them highly susceptible to oxidation and excludes them from use in extended experiments under aerobic conditions. Therefore, we have developed a set of novel TLR2 antagonists (1–9) based on the systematic variation of substructures, linker elements, and the hydrogen-bonding pattern of the pyrogallol precursors by using chemically robust building blocks. The novel series of chemically stable and synthetically accessible TLR2 antagonists (1–9) was pharmacologically characterized, and the potential binding modes of the active compounds were evaluated structurally. Our results provide new insights into structure-activity relationships and allow rationalization of structural binding characteristics. Moreover, they support the hypothesis that this class of TLR ligands bind solely to TLR2 and do not directly interact with TLR1 or TLR6 of the functional heterodimer. The most active compound from this series (6), is chemically stable, nontoxic, TLR2-selective, and shows a similar activity with regard to the pyrogallol starting points, thus indicating the variability of the hydrogen bonding pattern.

Lipidated Brartemicin Analogues Are Potent Th1-Stimulating Vaccine Adjuvants

Effective Th1-stimulating vaccine adjuvants typically activate antigen presenting cells (APCs) through pattern recognition receptors (PRRs). Macrophage inducible C-type lectin (Mincle) is a PRR expressed on APCs and has been identified as a target for Th1-stimulating adjuvants. Herein, we report on the synthesis and adjuvanticity of rationally designed brartemicin analogues containing long-chain lipids and demonstrate that they are potent Mincle agonists that activate APCs to produce inflammatory cytokines in a Mincle-dependent fashion. Mincle binding, however, does not directly correlate to a functional immune response. Mutation studies indicated that the aromatic residue of lead compound 9a has an important interaction with Mincle Arg183. In vivo assessment of 9a highlighted the capability of this analogue to augment the Th1 response to a model vaccine antigen. Taken together, our results show that lipophilic brartemicin analogues are potent Mincle agonists and that 9a has superior in vivo adjuvant activity compared to TDB.

Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase

Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro.

Benzoic hydroxamate-based iron complexes as model compounds for humic substances: Synthesis, characterization and algal growth experiments

A series of monomeric and dimeric FeIII complexes bearing benzoic hydroxamates as O,O-chelates has been prepared and characterized by elemental analysis, IR spectroscopy, UV-Vis spectroscopy, electrospray ionization mass spectrometry (ESI-MS), cyclic voltammetry, EPR spectroscopy and for some examples by X-ray diffraction analysis. The stability of the synthesized complexes in pure water and seawater was monitored over 24 h by means of UV-Vis spectrometry. The ability to release iron from the synthesized model complexes has been investigated with algae growth experiments.

RESORCINOL N-ARYL AMIDE COMPOUNDS, FOR USE AS PYRUVATE DEHYDROGENASE KINASE INHIBITORS

A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein: Y is –CONR1- or optionally substituted arylene or optionally substituted heteroarylene; R1 is H, Cl, F, CH3 or CF3; 10 each R4 is independently H, CH3 or F; R5 is H or CH3; and each R2 and R6 is independently (Alk)n-Rn-(Alk)n-Rn-(Alk)n-X; The compounds of the invention are useful as resorcinol N-aryl amide (NAA) compounds, which are suitable for use as PDK inhibitors, for example for 15 inhibition of cancer cell proliferation.

TETRAHYDROISOQUINOLINE COMPOUNDS AND THEIR USE AS PYRUVATE DEHYDROGENASE KINASE INHIBITORS

A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: R1 is H, Cl, F, CH3 or CF3; R2 is H, C1-C6 alkyl or optionally substituted heteroaryl or optionally substituted aryl; and R3 is (Alk)n-Rn-(Alk)n-Rn-(Alk)n-X. The compounds are useful as tetrahydroisoquinoline (THQ) compounds, which are suitable for use as PDK inhibitors, for example for inhibition of cancer cell proliferation.

Total syntheses of Nigrasin i and Kuwanon C

The efficient total syntheses of Nigrasin I and Kuwanon C, two biologically interesting natural flavonoids with two regioisomeric isoprenyl side chains, were realized for the first time starting from commercially available 1-(2,4,6-trihydroxyphenyl)ethano

Synthesis and antibacterial evaluation of anziaic acid and its analogues as topoisomerase i inhibitors

Naturally occurring anziaic acid has very recently been reported as a topoisomerase I inhibitor with antibacterial activity. Herein total synthesis of anziaic acid and its structural analogues is described and the preliminary structure-activity relationship (SAR) has been developed based on topoisomerase inhibition and whole cell antibacterial activity.

Synthesis and evaluation of C-ring aromatized analogues of phenanthridone alkaloids

Phenanthridone alkaloids are envisaged as an attractive lead for the development of anticancer agents. We have prepared a series of aromatized analogues on the basis of the structure of this class of alkaloids with the hope of finding the simplified compounds with comparable activities. The obtained analogues were evaluated for their cytotoxic effect against several cancer cell lines and found to be virtually inactive. These observations together with molecular modeling studies strongly suggest that the stereochemistries of hydroxyl groups in C-ring of phenanthridone alkaloids are crucial to biological effects.