33688-50-5

Usage

Type of compound

Benzyl ether derivative of 4-(chloromethyl)-2-methoxyphenol

Usage

Commonly used in organic synthesis

Physical state

Pale yellow solid

Odor

Slightly sweet

Solubility

Insoluble in water, soluble in organic solvents (e.g., ethanol and diethyl ether)

Applications

Used as a reagent in the synthesis of various organic compounds, and as an intermediate in the production of pharmaceuticals, agrochemicals, and other fine chemicals

Safety precautions

Potentially hazardous chemical, should be handled with care by trained professionals in a laboratory setting

InChI:InChI=1/C15H15ClO2/c1-17-15-9-13(10-16)7-8-14(15)18-11-12-5-3-2-4-6-12/h2-9H,10-11H2,1H3

Upstream product

• 100-44-7 benzyl chloride 
• 100-39-0 benzyl bromide 
• 121-33-5 vanillin 
• 498-00-0 4-hydroxymethyl-2-methoxyphenol 
• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 33693-48-0 4-benzyloxy-3-methoxybenzyl alcohol 

Downstream Products

• 1700-29-4 2-(4-(benzyloxy)-3-methoxyphenyl)acetonitrile 
• 77564-62-6 2-Benzyl-5,7-bis-benzyloxy-1-(4-benzyloxy-3-methoxy-benzyl)-1,2,3,4-tetrahydro-isoquinoline 
• 77564-70-6 2-Benzyl-5,7-bis-benzyloxy-1-(4-benzyloxy-3-methoxy-benzyl)-1,2-dihydro-isoquinoline 
• 70034-82-1 4-benzyloxy-3-methoxyphenyl-[1-13C]acetonitrile 
• 1160409-00-6 C₃₂H₃₅N₅O₃ 
• 67023-43-2 4-benzyloxy-3-methoxy-benzylamine 
• 915127-47-8 C₂₃H₁₉NO₄ 
• 18694-14-9 1-(4-(benzyloxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline 
• 41182-99-4 1-(4-(benzyloxy)-3-methoxybenzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 

Relevant academic research and scientific papers

Structure-based design, docking and binding free energy calculations of a366 derivatives as spindlin1 inhibitors

The chromatin reader protein Spindlin1 plays an important role in epigenetic regulation, through which it has been linked to several types of malignant tumors. In the current work, we report on the development of novel analogs of the previously published lead inhibitor A366. In an effort to improve the activity and explore the structure–activity relationship (SAR), a series of 21 derivatives was synthesized, tested in vitro, and investigated by means of molecular modeling tools. Docking studies and molecular dynamics (MD) simulations were performed to analyze and rationalize the structural differences responsible for the Spindlin1 activity. The analysis of MD simulations shed light on the important interactions. Our study highlighted the main structural features that are required for Spindlin1 inhibitory activity, which include a positively charged pyrrolidine moiety embedded into the aromatic cage connected via a propyloxy linker to the 2-aminoindole core. Of the latter, the amidine group anchor the compounds into the pocket through salt bridge interactions with Asp184. Different protocols were tested to identify a fast in silico method that could help to discriminate between active and inactive compounds within the A366 series. Rescoring the docking poses with MM-GBSA calculations was successful in this regard. Because A366 is known to be a G9a inhibitor, the most active developed Spindlin1 inhibitors were also tested over G9a and GLP to verify the selectivity profile of the A366 analogs. This resulted in the discovery of diverse selective compounds, among which 1s and 1t showed Spindlin1 activity in the nanomolar range and selectivity over G9a and GLP. Finally, future design hypotheses were suggested based on our findings.

Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products

Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.

Facile and Divergent Synthesis of Lamellarins and Lactam-Containing Derivatives with Improved Drug Likeness and Biological Activities

With the goal to improve the aqueous solubility of lamellarins, the lactone ring in their skeleton was replaced with a lactam moiety in azalamellarins. However, the reported synthetic route produced such derivatives in very low yields. Hence, this study focused on developing an efficient simplified total synthetic scheme that could furnish both azalamellarins and the parent lamellarins from the same pyrrole ester intermediates. Subsequent comparative profiling revealed that the introduced lactone-to-lactam replacement rendered these molecules less lipophilic, whereas their cancer cytotoxicity remained equipotent to that of the parent compounds. Interestingly, their inhibitory activity was significantly enhanced towards the multifaceted GSK-3β enzyme. Our results clearly demonstrate the therapeutic potential of this promising class of marine-derived natural products and justify their further development, especially into anticancer agents.

Chemical modifications of the N-methyl-laudanosine scaffold point to new directions for SK channels exploration

An asparagine or a histidine are present in a similar position in the outer pore region of SK2 and SK3 channels, respectively. Therefore, this structural difference was targeted in order to develop selective blockers of SK channel subtypes. Following docking investigations, based on theoretical models of truncated SK2 and SK3 channels, the benzyl side chain of N-methyl-laudanosine (NML) was functionalized in order to target this specific amino-acid residues. Chiral butanamide and benzyloxy analogues were prepared, resolved and tested for their affinity for SK2 and SK3 channels. Isoquinolinium (NMIQ) derivatives have a higher affinity for both SK channel subtypes than the corresponding derivative with no functionalized side chain. This trend was observed also for the 1,2,3,4-tetrahydroisoquinoline (THIQ) analogues. A benzyloxy functionalized NML enantiomer has a higher affinity than NML stereoisomers. Otherwise, the conserved affinity of these analogues led to the opportunity to further investigate in terms of possible labeling for in vivo investigations of the role of SK channels.

Discovery of novel 3-benzylquinazolin-4(3H)-ones as potent vasodilative agents

In the present study, a series of 3-benzylquinazolin-4(3H)-ones were synthesized and characterized. Their vasodilative effects were evaluated by wire myograph on isolated rat mesenteric arterial ring induced contraction with 60 mM KCl. The SAR of target compounds was discussed preliminarily. Among these compounds, 2a and 2c displayed potent vasodilatation action and could compete significantly the rat mesenteric arterial rings induced contraction with phenylephrine. Compounds 2a and 2c were further tested for their antihypertensive effects in SHR by oral administration. The results indicated that 2a and 2c could reduce significantly both diastolic and systolic blood pressure. Moreover, 2c displayed antihypertensive effect in a dose dependent manner, and could maintain the effects for 6 h at a dosage of 4.0 mg/kg. These findings suggest that the title compounds are novel vasodilative agents, representing a novel series of promising antihypertensive agents.

Gem-substituted αvβ3 antagonists

The present invention relates to a class of compounds represented by the Formula I. or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of the Formula I, and methods of selectively inhibiting or antagonizing the αVβ3and/or the αVβ5integrin.

Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents

Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC50 = 15 nM) was shown to be a potent inhibitor of tubulin polymerization.

Incorporation of phenethylisoquinolines into colchicine in isolated seeds of Colchicum autumnale

The physiological parameters for application experiments using immature seeds of Colchicum autumnale were optimized, so that incorporation rates in the range of 10% and higher were consistently obtained with intermediate precursors. Application of tritium and 13C-labelled phenethylisoquinolines showed that N-methylation occurs prior to the substitution of ring C and that the free hydroxy group in position 13 of autumnaline is necessary for the phenolic coupling reaction. Autumnaline gives rise to a vast array of metabolites in seeds of this plant.

Identification and synthesis of a methylated catechol metabolite of glutethimide isolated from biological fluids of overdose victims

Urine samples from victims severely intoxicated by glutethimide were hydrolyzed enzymatically. TLC, GLC, and mass spectral analyses revealed a methylated catechol metabolite of the parent drug. Two synthetic pathways are described for the preparation of 2-ethyl-2-(3-methoxy-4-hydroxyphenyl)glutarimide and 2-ethyl-2-(3-hydroxy-4-methoxyphenyl)glutarimide. Comparisons of GLC and mass spectral data to a compound isolated from the body fluids of glutethimide overdose victims conclusively identified a new 3-methoxy-4-hydroxyphenyl metabolite of glutethimide in humans.