27115-50-0

Usage

Uses

Used in Pharmaceutical Industry:
4-METHYLHIPPURIC ACID is used as a substrate and inhibitor for peptidylglycine α-hydroxylating monooxygenase (PHM) for studying enzyme activity and inhibition in the pharmaceutical industry. This application helps in understanding the enzyme's role in various biological processes and can contribute to the development of new drugs targeting this enzyme.
Used in Environmental and Occupational Health:
4-METHYLHIPPURIC ACID is used as a biomarker for exposure to xylene, an industrial solvent, in environmental and occupational health assessments. The detection of this metabolite in urine samples can indicate the level of exposure to xylene, which is crucial for monitoring worker safety and environmental contamination.
Used in Toxicology Research:
4-METHYLHIPPURIC ACID is used as a research tool in toxicology to study the metabolism and toxic effects of xylene and other related compounds. This application aids in understanding the mechanisms of toxicity and can help in the development of strategies to mitigate the harmful effects of these chemicals on human health and the environment.

InChI:InChI=1/C10H17NO3/c1-7-2-4-8(5-3-7)10(14)11-6-9(12)13/h7-8H,2-6H2,1H3,(H,11,14)(H,12,13)/p-1

Upstream product

• 122081-29-2 N-(4-methyl)benzoyl glycine ethylester 
• 874-60-2 4-methyl-benzoyl chloride 
• 56-40-6 glycine 
• 99-94-5 p-Toluic acid 
• 42469-26-1 N-(2-hydroxyethyl)-4-methylbenzamide 
• 22198-21-6 N-p-toluoyl-glycine nitrile 
• 75152-18-0 2-p-tolyl-4H-oxazol-5-one 

Downstream Products

• 16352-80-0 4-furfurylidene-2-p-tolyl-4H-oxazol-5-one 
• 75152-14-6 (4-Methyl-benzoylamino)-acetic acid 4-nitro-phenyl ester 
• 116222-15-2 3-(4-Methyl-benzoylamino)-2-oxo-1,2-dihydro-quinoline-4-carboxylic acid phenylamide 
• 126325-45-9 N-(8-Hydroxy-2-oxo-2H-chromen-3-yl)-4-methyl-benzamide 
• 116222-17-4 3-(4-Methyl-benzoylamino)-2-oxo-1,2-dihydro-quinoline-4-carboxylic acid (4-methoxy-phenyl)-amide 
• 57427-79-9 (Z)-4-(4-methylbenzylidene)-2-phenyloxazol-5(4H)-one 
• 126325-44-8 4-methyl-N-(coumarin-3-yl)benzamide 
• 126325-40-4 5-[1-(2-Hydroxy-phenyl)-meth-(Z)-ylidene]-3-phenyl-2-p-tolyl-3,5-dihydro-imidazol-4-one 
• 126325-41-5 2-p-toluoylamino-o-hydroxycinnamanilide 
• 135520-96-6 4-m-methoxy-p-hydroxybenzylidene-2-p-toluyl-2-oxazolin-5-one 
• 135520-95-5 4-m-methoxy-p-hydroxybenzylidene-2-p-toluyl-1-phenyl-2-imidazolin-5-one 
• 135520-97-7 2-N-p-toluoylamino-m-methoxy-p-hydroxycinnamanilide 
• 72615-45-3 2-o-Tolyl-4-[1-p-tolyl-meth-(Z)-ylidene]-4H-oxazol-5-one 
• 103369-10-4 [(4-methylbenzoyl)amino]methyl acetate 

Relevant academic research and scientific papers

Synthesis and evaluation of new phenyl acrylamide derivatives as potent non-nucleoside anti-HBV agents

As a continuation of our previous work, a series of new phenyl acrylamide derivatives (4Aa-g, 4Ba-t, 5 and 6a-c) were designed and synthesized as non-nucleoside anti-HBV agents. Among them, compound 4Bs could potently inhibit HBV DNA replication in wild-type and lamivudine (3TC)/entecavir resistant HBV mutant strains with IC50 values of 0.19 and 0.18 μM, respectively. Notably, the selective index value of 4Bs was above 526, indicating the favorable safety profile. Interestingly, unlike nucleoside analogue 3TC, 4Bs could significantly inhibit 3.5 kb pgRNA expression. Molecular docking study revealed that 4Bs could fit well into the dimer-dimer interface of HBV core protein by hydrophobic, π–π and H-bond interactions. Considering the potent anti-HBV activity, low toxicity and diverse anti-HBV mechanism from that of nucleoside anti-HBV agent 3TC, compound 4Bs might be a promising lead to develop novel non-nucleoside anti-HBV therapeutic agents, and warranted further investigation.

Nickel-Catalyzed Asymmetric Hydrogenation of 2-Amidoacrylates

Earth-abundant nickel, coordinated with a suitable chiral bisphosphine ligand, was found to be an efficient catalyst for the asymmetric hydrogenation of 2-amidoacrylates, affording the chiral α-amino acid esters in quantitative yields and excellent enantioselectivity (up to 96 % ee). The active catalyst component was studied by NMR and HRMS, which helped us to realize high catalytic efficiency on a gram scale with a low catalyst loading (S/C=2000). The hydrogenated products could be simply converted into chiral α-amino acids, β-amino alcohols, and their bioactive derivatives. Furthermore, the catalytic mechanism was investigated using deuterium-labeling experiments and computational calculations.

Synthesis, Spectroscopic Characterization and Polymerization Abilities of Blue and Green Light Emitting Oxazol-5-one Fluorophores

New fluorescent thiophenyl group containing oxazol-5-one fluorophores of 3a (4-(3-thiophenylmethylene)-2-phenyloxazol-5-one), 3b (4-(3-thiophenylmethylene)-2-(4-tolyl)oxazol-5-one) and 3c (4-(3-thiophenylmethylene)-2-(4-nitrophenyl)oxazol-5-one) were synthesized and characterized. The newly synthesized oxazol-5-ones absorption and fluorescence characteristics were studied in some solvents of varying polarities. The heterocyclic chromophores were fluorescent, with two of them, 3a and 3b, emitting blue light, whilst the other one, 3c, emitting green light. The emission maxima of the derivatives varied between 415 and 572?nm according as the extent of conjugation and solvent polarity. As solvent polarity increased, 3c derivatives emission spectra displayed a large bathochromic shift, which revealed the considerable change of the dipole moment of the fluorescent structure because of an intramolecular charge transfer interaction. Furthermore, oxazolones polymerization ability via the thiophenyl group linked to the oxazol-5-one heterocycle showed that copolymerization of 3a was achieved, but homopolymerization was not observed.

Synthesis and cytotoxicity of novel dispiro derivatives of 5-arylidenoxazolones, potential inhibitors of p53—MDM2 protein-protein interaction

Regioselective synthesis of new dispiro indolinones combining both an indolinone and an oxazolone fragment in their structure comprised the 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from isatin and sarcosine, at 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4H)-ones. When ortho and para halogen atoms were present in the aromatic substituents of the starting oxazolones, complex mixtures containing large amounts of oxazoline ring opening products and their dispiro derivatives were formed. The cytotoxicity of compounds was tested by MTT on LNCaP, PC3, HCT116, MCF7, A549, HEK, and VA13 cell lines. The compound possessing the best cytotoxicity revealed the IC50 = 1.08±0.96 μM towards the p53- expressing LNCaP cells and lower activity (IC50 = 3.21±1.45 μM) towards the non-expressing p53 protein PC3 cells, however, it has proved inactive towards the HCT cells, both expressing (HCТ+/+) and non-expressing (HCT–/–) p53.

Supported ruthenium hydride catalysts for direct conversion of alcohols to carboxylic acids using styrene oxide as oxidant

In the present work, the ability of two ruthenium hydride catalysts supported on multiwall carbon nanotubes, [Ru–H@EDT–MWCNT], and gold nanoparticles cored triazine dendrimer, [Ru–H@AuNPs–TD], in the direct conversion of alcohols to carboxylic acids via transfer hydrogenation using styrene oxide as oxidant is reported. Different alcohols were successfully converted to their corresponding carboxylic acids. The results showed that these two heterogeneous catalysts are more efficient than the homogeneous counterpart. In addition, the catalysts were reused several times.

Design, Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of Imidazolone Fused Pyrazolo[1,5-a]pyrimidine Derivatives

A novel series of imidazolone fused pyrazolo[1,5-a]pyrimidine derivatives has been designed and synthesized using a convergent approach, and the structures of these compounds were confirmed by 1H NMR, 13C NMR, ESI-MS, and IR analyses. These new compounds were tested for their in vitro antiproliferative activity using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Out of the 20 derivatives prepared in the current study, compounds 8h, 8n, and 8r exhibited good anticancer activities tested against HeLa cells and HepG2 cells. However, the in vitro anticancer activity of compound 8r against HeLa, HepG2, and MCF-7 cell lines is superior to the marketed drugs Paclitaxel and SAHA.

Synthesis and characterization of new green and orange region emitting anthracene based oxazol-5-one dyes

New anthracene oxazol-5-one dyes featuring an extended π-conjugated electron system have been successfully prepared by Erlenmeyer synthesis, structurally characterized and their spectroscopic properties were investigated by UV–vis absorption spectroscopy and fluorescence spectroscopy. The oxazol-5-ones were attached to the 9-position of the anthracene to obtain the desired structures. The dyes are having extended conjugation throughout their structure with oxazol-5-one ring as the chromophore. The spectral properties of the oxazol-5-one ring were monitored with respect to the substituents at the phenyl ring. All of the dyes synthesized show good solubility in common organic solvents. Also in order to establish whether there was any solvent affects the absorption and emission spectra of the compounds were measured in the solvents of acetonitrile, tetrahydrofuran and chloroform which have different polarity. Moreover, their absorption and emission properties were investigated in plasticized PVC film matrix. In comparison to the solution phase, the dyes displayed enhanced fluorescence emission quantum yield values when embedded in poly(vinyl chloride) polymer film. The anthracene based oxazol-5-ones were found to emit in the green portion of the spectrum for 2a and 2b, and in the orange portion of the spectrum for 2c. By attachment of nitro substituent at the para position of the phenyl ring bound to oxazol-5-one core, the fluorescence maxima could be effectively modulated from the green region of the spectra to the orange region. 4-(9-anthralydene)-2-(4-nitrophenyl)oxazol-5-one (2c) exhibits large Stokes shift up to 146 nm presumably due to intramolecular charge transfer.

Synthesis and biological testing of (5Z)-2-aryl-5-arylmethylidene-3,5-dihydro-4H-imidazol-4-ones as antimitotic agents

Compounds interacting with cell protein tubulin and microtubules represent an important type of antimitotic agents. A series of tubulin-targeted 2-aryl-4-benzoyl-imidazoles were reported to possess high cytotoxicity, and so, we prepared a series of structural isomers of these to be evaluated as antimitotic agents. The synthesis of the novel (Z)-2-aryl-5-arylmethylidene-3,5-dihydro-4H-imidazol-4-ones involved coupling of substituted hippuric acids with aromatic aldehydes. Subsequent conversion of the resulting oxazolones to the corresponding imidazolones was carried out under microwave irradiation in the presence of urea and ammonium acetate. The cytotoxicity of the majority of the compounds to human epithelial carcinoma cancer cell line A549 was in the sub-micromolar range and was found to be more sensitive to the substituents on the 5-arylmethylidene fragment than on the 2-aryl ring in general. The cytotoxicities of the synthesized compounds were lower than those of the previously reported isomeric 2-aryl-4-benzoyl-imidazoles, and the basic structure–activity relationships in the isomeric pairs were different. Synthesized (5Z)-5-[(4-bromophenyl)methylidene]-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one, which had the highest cytotoxicity (IC50?~?440?nM) in the series of novel compounds, had a definite cytostatic effect on the A549 cells, but its antiproliferative properties were not linked to action on the microtubules. This would be an interesting lead compound for additional investigation into the mechanism of cytostatic action, and further structural optimization.

Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication

A series of new arylpropenamide derivatives containing different aryl groups were synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV) activities. A new high accuracy QSAR model of arylpropenamide was constructed based on a more completely activities data and calculation parameter. The 2D-QSAR equations, by using DFT and multiple linear regression analysis methods, revealed that higher value of thermal energy (TE) and lower entropy (S?) increase the anti-HBV activities of the arylpropenamide molecules. Predictive 3D-QSAR models were established by SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross-validated and conventional coefficients, indicating that they were reliable enough for activity prediction.

Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy

Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure-activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (ICinf50/inf values 0.141/4M) and cell-free assays (ICinf50/inf values 0.03 1/4M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy.