2186-24-5

Usage

Uses

Used in Pharmaceutical Synthesis:
2-P-TOLYLOXYMETHYL-OXIRANE is used as a key intermediate in the synthesis of 3-aryloxy-1,2-epoxypropanes. These compounds serve as potential synthons in the preparation of β-adrenergic receptor antagonists, which are important drugs for the treatment of various cardiovascular and respiratory conditions. The synthesis of these compounds is typically carried out under solvent-free conditions and microwave irradiations, which offer advantages such as reduced reaction times, improved yields, and reduced environmental impact.
Used in Chemical Research:
In addition to its applications in pharmaceutical synthesis, 2-P-TOLYLOXYMETHYL-OXIRANE is also used as a starting material or building block in various chemical research projects. Its unique structural features make it a valuable compound for exploring new reaction pathways, developing novel synthetic methods, and designing new molecules with potential applications in various fields, including materials science, agrochemistry, and environmental chemistry.

InChI:InChI=1/C10H12O2/c1-8-2-4-9(5-3-8)11-6-10-7-12-10/h2-5,10H,6-7H2,1H3

Upstream product

• 79-21-0 peracetic acid 
• 23431-48-3 allyl p-tolyl ether 
• 106-44-5 p-cresol 
• 96-23-1 1,3-Dichloro-2-propanol 
• 106-89-8 epichlorohydrin 
• 4769-74-8 1-chloro-3-(4-methylphenoxy)-2-propanol 
• 118712-54-2 glycidyl p-toluenesulfonate 
• 68224-00-0 2-(2-Bromo-4-methyl-phenoxymethyl)-oxirane 
• 6627-55-0 2-bromo-p-cresol 
• 3132-64-7 1,2-Epoxy-3-bromopropane 

Downstream Products

• 5296-17-3 F₃₂₅₄-0053 
• 133132-07-7 1-(2-methyl-pyrrolidino)-3-p-tolyloxy-propan-2-ol 
• 107410-26-4 1-propylamino-3-p-tolyloxy-propan-2-ol; hydrochloride 
• 110080-42-7 1-(4-phenyl-piperazino)-3-p-tolyloxy-propan-2-ol 
• 110531-03-8 1-(4-methylphenoxy)-3-[4-(4-methylphenyl)piperazin-1-yl]propan-2-ol 
• 110530-97-7 1-p-tolyloxy-3-(4-m-tolyl-piperazino)-propan-2-ol 
• 112864-99-0 1-[4-(4-chloro-phenyl)-piperazino]-3-p-tolyloxy-propan-2-ol 
• 110531-00-5 1-p-tolyloxy-3-(4-o-tolyl-piperazino)-propan-2-ol 
• 110148-33-9 1-[4-(2-chloro-phenyl)-piperazino]-3-p-tolyloxy-propan-2-ol 
• 115322-09-3 1-(4-Ethoxycarbonyl-4-phenyl-piperidino)-3-p-tolyloxy-propanol-(2) 
• 105254-17-9 1-ethylamino-3-p-tolyloxy-propan-2-ol 
• 107916-88-1 1-diethylamino-3-p-tolyloxy-propan-2-ol 
• 107916-87-0 1-butylamino-3-p-tolyloxy-propan-2-ol; hydrochloride 
• 39144-40-6 1-methoxy-3-p-tolyloxy-propan-2-ol 

Relevant academic research and scientific papers

Synthesis and evaluation of 4-(2-hydroxypropyl)piperazin-1-yl) derivatives as Hsp90 inhibitors

We previously reported 4-(3-((6-bromonaphthalen-2-yl)oxy)-2-hydroxypropyl)-N,N-dimethylpiperazine-1-sulfonamide (1) as a novel heat shock protein 90 inhibitor with moderate activity. In our ongoing efforts for the discovery of Hsp90 modulators we undertake structural investigations on 1. Series of the titled compound were designed, synthesized and evaluated. We have found that compounds with a hydroxyl group at C-4 of the aryl ring on the piperazine moiety possess Hsp90 inhibition properties. Compound 6f with improved activity could be further developed and optimized as Hsp90 inhibitor.

Discovery of a Potent and Selective Chikungunya Virus Envelope Protein Inhibitor through Computer-Aided Drug Design

The worldwide expansion of chikungunya virus (CHIKV) into tropical and subtropical areas in the last 15 years has posed a currently unmet need for vaccines and therapeutics. The E2-E1 envelope glycoprotein complex binds receptors on the host cell and promotes membrane fusion during CHIKV entry, thus constituting an attractive target for the development of antiviral drugs. In order to identify CHIKV antivirals acting through inhibition of the envelope glycoprotein complex function, our first approach was to search for amenable druggable sites within the E2-E1 heterodimer. We identified a pocket located in the interface between E2 and E1 around the fusion loop. Then, via a structure-based virtual screening approach and in vitro assay of antiviral activity, we identified compound 7 as a specific inhibitor of CHIKV. Through a lead optimization process, we obtained compound 11 that demonstrated increased antiviral activity and low cytotoxicity (EC50 1.6 μM, CC50 56.0 μM). Molecular dynamics simulations were carried out and described a possible interaction pattern of compound 11 and the E1-E2 dimer that could be useful for further optimization. As expected from target site selection, compound 11 inhibited virus internalization during CHIKV entry. In addition, virus populations resistant to compound 11 included mutation E2-P173S, which mapped to the proposed binding pocket, and second site mutation E1-Y24H. Construction of recombinant viruses showed that these mutations conferred antiviral resistance in the parental background. Finally, compound 11 presents acceptable solubility values and is chemically and enzymatically stable in different media. Altogether, these findings uncover a suitable pocket for the design of CHIKV entry inhibitors with promising antiviral activity and pharmacological profiles.

Chemoselective Epoxidation of Allyloxybenzene by Hydrogen Peroxide Over MFI-Type Titanosilicate

The chemoselective synthesis of 2-(phenoxymethyl)oxirane from allyloxybenzene is achieved with over 90 % yield in a sustainable reaction system using titanium-substituted silicalite-1 (TS-1) as a catalyst, hydrogen peroxide (H2O2) as an oxidant, and a mixture of MeOH/MeCN as a solvent at 40 °C. No acid-catalyzed side reactions prompted by the Lewis acidity of the Ti active site in TS-1 are observed. The TS-1 catalyst can also promote the formation of oxiranes from various p-substituted allyloxybenzenes in good yields. The reaction mechanism is investigated through the reaction with other allyloxy compounds. The results, which are supported by DFT calculations, indicate that an active species of Ti peroxides formed from the reaction of TS-1 with H2O2 selectively oxidizes the allyloxybenzene to 2-(phenoxymethyl)oxirane.

NBS/DMSO-mediated synthesis of (2,3-dihydrobenzo[b] [1,4]oxathiin-3-yl)methanols from aryloxymethylthiiranes

(2,3-Dihydrobenzo[b][1,4]oxathiin-3-yl)methanols were synthesized via reactions of aryloxymethylthiiranes and N-bromosuccinimide (NBS) in DMSO under microwave irradiation. The reaction mechanism was proposed as an intramolecular aromatic electrophilic substitution of 1-bromo-2-(aryloxymethyl)thiiran-1-iums, generated from aryloxymethylthiiranes and NBS, and the subsequent DMSO nucleophilic ring opening reaction of thiiran-1-iums followed by the water displacement. The current method provides a direct and simple strategy in the efficient preparation of (2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanols from readily available aryloxymethylthiiranes.

NOVEL DIEPOXY COMPOUND

PROBLEM TO BE SOLVED: To provide a novel diepoxy compound which has liquid crystalline properties and is excellent in thermal conductivity and heat resistance. SOLUTION: The problem is solved by using a diepoxy compound represented by the general formula (1) in the figure. (In the formula, R1 represents an oxygen atom or methylene group; R2 represents a methylene group if R1 is an oxygen atom, and represents an oxygen atom if R1 is a methylene group; R3 represents a hydrogen atom or methyl group; and n represents 0 or 1.) SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

Facile synthesis of thietanes via ring expansion of thiiranes

Thietanes are pharmaceutically important cores of some biological compounds and intermediates of organic synthesis. Various thietanes were prepared from thiiranes via ring expansion through a reaction with trimethyloxosulfonium iodide in the presence of sodium hydride. The reaction process is a nucleophilic ring-opening reaction of thiiranes with dimethyloxosulfonium methylide, generated from trimethyloxosulfonium iodide and sodium hydride, and subsequent intramolecular displacement (cyclization) of thiolates to the dimethyloxosulfonium moiety. The current method provides a new strategy for efficient preparation of thietanes from readily available thiiranes.

Synthesis of 2-(phenoxymethyl)oxirane derivatives through unexpected rearrangement of oxiran-2-ylmethyl benzenesulfonates

The synthesis of 2-(phenoxymethyl)oxirane derivatives from oxiran-2-ylmethyl benzenesulfonates was developed through a base promoted rearrangement. A new C-O bond was formed along with the unexpected cleavage of C-S bond via this process. This unusual reaction was characterized with mild reaction conditions, high efficiency, and excellent functional group tolerance. A plausible reaction mechanism was proposed on the basis of experimental results and control experiments.

Design, synthesis and biological evaluation of novel 1,2,3-triazolyl β -hydroxy alkyl/carbazole hybrid molecules

The design, synthesis and biological study of several novel 1,2,3-triazolyl β -hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl)-9H-carbazole. The ‘Click’ Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9H-carbazole with diverse β -azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram-negative bacteria. In particular, 1-(4-((9H-carbazol-9-yl) methyl)-1H-1,2,3-triazol-1-yl)-3-butoxypropan-2-ol (10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between β -hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a–10n as potential lead antifungal agents for future investigations.

THERAPEUTIC COMPOUNDS

The present invention relates to therapeutic compounds useful for the treatment of neurodegenerative and neuromuscular diseases and/or triplet repeat diseases (e.g. Friedreich's ataxia). The compounds have the structural formula I shown below: wherein Q, X, p, R1, q, R3 and R4 are as defined herein. The present invention also relates to pharmaceutical compositions comprising the compounds defined herein, the use of these compositions for the treatment of neurodegenerative and neuromuscular diseases and/or triplet repeat diseases (e.g. Friedreich's ataxia), and to processes for the preparation of the pharmaceutical compositions defined herein.

An unusual (R)-selective epoxide hydrolase with high activity for facile preparation of enantiopure glycidyl ethers

A novel epoxide hydrolase (BMEH) with unusual (R)-enantioselectivity and very high activity was cloned from Bacillus megaterium ECU1001. Highest enantioselectivities (E>200) were achieved in the bioresolution of ortho-substituted phenyl glycidyl ethers and para-nitrostyrene oxide. Worthy of note is that the substrate structure remarkably affected the enantioselectivities of the enzyme, as a reversed (S)-enantiopreference was unexpectedly observed for the ortho-nitrophenyl glycidyl ether. As a proof-of-concept, five enantiopure epoxides (>99% ee) were obtained in high yields, and a gram-scale preparation of (S)-ortho-methylphenyl glycidyl ether was then successfully performed within a few hours, indicating that BMEH is an attractive biocatalyst for the efficient preparation of optically active epoxides. Copyright