536-25-4

Usage

Chemical Properties

Beige Solid

Uses

Anesthetic (topical).

InChI:InChI=1/C8H9NO3/c1-12-8(11)5-2-3-7(10)6(9)4-5/h2-4,10H,9H2,1H3

Upstream product

• 99-42-3 methyl (4-hydroxy-3-nitro)benzoate 
• 67-56-1 methanol 
• 1571-72-8 3-amino-4-hydroxybenzoic acid 
• 91-66-7 N,N-diethylaniline 
• 616-82-0 3-nitro-4-hydroxybenzoic acid 
• 75-36-5 acetyl chloride 
• 18107-18-1 diazomethyl-trimethyl-silane 

Downstream Products

• 136663-21-3 methyl 2-methyl-1,3-benzoxazole-5-carboxylate 
• 126360-59-6 methyl 3-(N-acetyl)amino-4-hydroxybenzoate 
• 82525-66-4 3-(2-chloro-acetylamino)-4-hydroxy-benzoic acid methyl ester 
• 82525-67-5 4-hydroxy-3-{[N-(2-hydroxy-5-methoxycarbonyl-phenyl)-glycyl]-amino}-benzoic acid methyl ester 
• 31039-94-8 4-hydroxy-3-phenylazo-benzoic acid methyl ester 
• 72730-39-3 methyl 2-thioxo-2,3-dihydrobenzo[d]oxazole-5-carboxylate 
• 65422-70-0 methyl 2-oxo-2,3-dihydro-1,3-benzoxazole-5-carboxylate 
• 6332-66-7 3-(2-carbamoylsulfanyl-acetylamino)-4-hydroxy-benzoic acid methyl ester 
• 5852-78-8 8-hydroxy-quinoline-5-carboxylic acid 
• 220844-97-3 methyl 4-hydroxy-3-methylaminobenzoate 
• 316158-20-0 methyl 3-(dimethylamino)-4-hydroxybenzoate 

Relevant academic research and scientific papers

Synthesis and biological activities of some Novel 2-Amino-(5 or 7-Substituted- 2-Oxoindolin-3-Ylidene) Benzoxazole-5-Carbohydrazide derivatives

A series of 2-amino-(5 or 7-substituted-2-oxoindolin-3-ylidene) benzoxazole-5-carbohydrazide derivatives were synthesized by treating 2-aminobenzoxazole-5-carbohydrazide with different substituted isatins. All the synthesized derivatives (VI a-l) were screened for their in vitro anticancer (against HeLa, IMR-32 & MCF-7 cancer cell lines), antioxidant (against DPPH radicals) and antimicrobial activities. The results of these studies showed the dose dependant anticancer, antioxidant and antimicrobial activities of the test compounds and the IC50 values of some compounds were comparable with their standard agent. The test compounds having substitution with different electron withdrawing groups at C-5 position showed more potent anticancer, antioxidant and antibacterial activities than those at C-7 position.

Sulfatase-cleavable linkers for antibody-drug conjugates

Antibody-drug conjugates (ADCs) are a class of targeted drug delivery agents combining the cell-selectivity of monoclonal antibodies (mAbs) and the cytotoxicity of small molecules. These two components are joined by a covalent linker, whose nature is critical to the efficacy and safety of the ADC. Enzyme-cleavable dipeptidic linkers have emerged as a particularly effective ADC linker type due to their ability to selectively release the payload in the lysosomes of target cells. However, these linkers have a number of drawbacks, including instability in rodent plasma and their inherently high hydrophobicity. Here we show that arylsulfate-containing ADC linkers are cleaved by lysosomal sulfatase enzymes to tracelessly release their payload, while circumventing the instability problems associated with dipeptide-linkers. When incorporated with trastuzumab and the highly potent monomethyl auristatin E (MMAE) payload, the arylsulfate-containing ADC 2 and ADC 3 were more cytotoxic than the non-cleavable ADC 4 against HER2-positive cells, while maintaining selectivity over HER2-negative cells. We propose that the stability, solubility and synthetic tractability of our arylsulfate linkers make them an attractive new motif for cleavable ADC linkers, with clear benefits over the widely used dipeptidic linkers.

Heterocyclic substituted biphenyl compound as well as preparation method and application thereof

The invention discloses a heterocyclic substituted biphenyl compound as well as a preparation method and application thereof. According to the present invention, the compound can block the PD-1/PD-L1 signal pathway, and can be used as the immune checkpoint PD-1/PD-L1 small molecule inhibitor; and according to the compound disclosed by the invention, the metabolic stability is improved while the high binding rate with PD-L1 protein is maintained. A hydrophilic group is introduced to a heterocyclic ring, and the PD-1/PD-L1 inhibitory activity is improved.

Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors

Fe(II)/α-ketoglutarate-dependent lysine demethylases (KDMs) are attractive drug targets for several diseases including cancer. In this study, we designed and screened ortho-substituted anilides that are expected to function as Fe(II) chelators, and identified ortho-hydroxy anilide as a novel scaffold for KDM5A inhibitors. Treatment of human lung cancer A549 cells with a prodrug form of 4-carboxy-2-hydroxy-formanilide (9c) increased trimethylated lysine 4 on histone H3 level, suggesting KDM5 inhibition in the cells.

Synthesis, Structure Revision, and Cytotoxicity of Nocarbenzoxazole G

The total synthesis of nocarbenzoxazoles F (1) and G (2), originally obtained from the marine-derived halophilic bacterial strain Nocardiopsis lucentensis DSM 44048, was achieved via a simple and versatile route involving microwave-assisted construction of a benzoxazole skeleton, followed by carbon-carbon bond formation with the corresponding aryl bromides. Unfortunately, the 1H and 13C NMR spectra of natural nocarbenzoxazole G did not agree with those of the synthesized compound. In particular, the spectra of the isolated and synthesized compounds showed considerable differences in the signals from the protons and carbons in the aryl group. The revised structure was validated by the total synthesis of the actual nocarbenzoxazole G (8c) molecule, which is a regioisomer of the compound that was reported earlier as nocarbenzoxazole G. The synthesized derivatives showed specific cytotoxicity to the human cervical carcinoma cell line, HeLa, but did not have any remarkable effect on the other cell lines.

Design, synthesis and pharmacology of aortic-selective acyl-CoA: Cholesterol O-acyltransferase (ACAT/SOAT) inhibitors

We describe our molecular design of aortic-selective acyl-coenzyme A:cholesterol O-acyltransferase (ACAT, also abbreviated as SOAT) inhibitors, their structure–activity relationships (SARs) and their pharmacokinetic (PK) and pharmacological profiles. The connection of two weak ligands—N-(2,6-diisopropylphenyl)acetamide (50% inhibitory concentration [IC50] = 8.6 μM) and 2-(methylthio)benzo[d]oxazole (IC50 = 31 μM)—via a linker comprising a 6 methylene group chains yielded a highly potent molecule, 9-(benzo[d]oxazol-2-ylthio)-N-(2,6-diisopropylphenyl)nonanamide (3h) that exhibited high potency (IC50 = 0.004 μM) toward aortic ACAT. This head-to-tail design made it possible to markedly enhance the activity to 2150- to 7750-fold and to discriminate the isoform-selectivity based on the double-induced fit mechanism. At doses of 1 and 3 mg/kg, 3h significantly decreased the lipid-accumulation areas in the aortic arch to 74 and 69%, respectively without reducing the plasma total cholesterol level in high fat- and cholesterol-fed F1B hamsters. Here, we demonstrate the antiatherosclerotic effect of 3h in vivo via its direct action on aortic ACAT and its powerful modulator of cholesterol level. This molecule is a potential therapeutic agent for the treatment of diseases involving ACAT-1 overexpression.

HEPATITIS B CORE PROTEIN MODULATORS

The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound of formula:

High Performance and Active Sites of a Ceria-Supported Palladium Catalyst for Solvent-Free Chemoselective Hydrogenation of Nitroarenes

Cerium oxide-supported palladium catalysts (Pd/CeO2) prepared by a simple impregnation method exhibit exciting catalytic activity and high chemoselectivity for the solvent-free hydrogenation of a variety of substituted nitroarenes including the reducible functional groups to the corresponding aromatic amines under mild reaction conditions. Taking nitrobenzene as an example, the Pd/CeO2 catalyst can afford aniline yields of >99 % with turnover frequencies as high as 11 411 h?1 and 69 824 h?1 at 40 °C and 100 °C, respectively. Pd2+ ion species exist as isolated single atoms with ?Pd2+?O2??Ce4+? linkages on the surface of PdxCe1?xO2?σ solid solution and are found to be active sites for the selective hydrogenation of nitroarenes in the absence of solvent. The superior catalytic performance can be attributed to the cooperative effect between Pd2+ ions and unique surface sites of CeO2. A possible mechanism is proposed for the hydrogenation of nitroarenes with H2 over the Pd/CeO2. The Pd/CeO2 catalyst can be recovered easily and reused for at least seven recycling reactions without loss of catalytic properties.

Design, Synthesis, and in Vitro and in Vivo Evaluation of an 18F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer

Sphingosine 1-phosphate receptor 1 (S1P1) plays a pivotal signaling role in inflammatory response; because S1P1 modulation has been identified as a therapeutic target for various diseases, a PET tracer for S1P1 would be a useful tool. Fourteen fluorine-containing analogues of S1P ligands were synthesized and their in vitro binding potency measured; four had high potency and selectivity for S1P1 (S1P1 IC50 100-fold selectivity for S1P1 over S1P2 and S1P3). The most potent ligand, 28c (IC50 = 2.63 nM for S1P1) was 18F-labeled and evaluated in a mouse model of LPS-induced acute liver injury to determine its S1P1-binding specificity. The results from biodistribution, autoradiography, and microPET imaging showed higher [18F]28c accumulation in the liver of LPS-treated mice than controls. Increased expression of S1P1 in the LPS model was confirmed by immunohistochemical analysis (IHC). These data suggest that [18F]28c is a S1P1 PET tracer with high potential for imaging S1P1 in vivo.

Benzoin oxazole derivatives, preparation method thereof and pharmaceutical compositions that contain them

Benzoxazole derivatives novel benzo the present invention refers to, effect because of having immunosuppressive effect and manufacturing method thereof including obesity and obesity related metabolic diseases in particular, various diabetes and medicament for the prophylaxis or treatment of diseases associated with diabetes is directed to compositions. Benzoxazole derivatives novel benzo of the present invention a sugar-dependent insulin secretion [...] to increase the weight of an increase in the activity of suppression effect on GPR119 (G protein-coupled receptor 119) by efficiently antifungal is and lipid metabolism per, as well as diabetes, obesity, hyperlipidemia, diabetic vascular disease of a polyimide resin, such data structure for complications diabetes for prophylactic and therapeutic composition can be useful