75541-63-8

Upstream product

• 103-82-2 phenylacetic acid 
• 134-20-3 2-carbomethoxyaniline 
• 67-56-1 methanol 
• 118-92-3 anthranilic acid 
• 536-74-3 phenylacetylene 
• 28861-34-9 phenylacetylcarbamic acid methyl ester 
• 88284-48-4 2-(trimethylsilyl)phenyl trifluoromethanesulfonate 
• 103-80-0 phenylacetyl chloride 

Downstream Products

• 84374-72-1 2-benzyl-4H-3,1-benzothiazine-4-thione 
• 14933-29-0 4-hydroxy-3-phenyl-2(1H)-quinolone 
• 28565-98-2 N-phenylacetylanthranilic acid 
• 174575-88-3 N-(2-carbomethoxyphenyl)-3-hydroxy-4-phenylmaleinimide 
• 58980-13-5 2-benzyl-4H-3,1-benzoxazine-4-one 
• 107618-47-3 2-benzyl-benzo[d][1,3]thiazin-4-one 
• 19857-34-2 2-(phenylmethyl)-3-phenyl-4(3H)-quinazolinone 

Relevant academic research and scientific papers

O-amino aromatic amide derivative as well as preparation method and application thereof

The invention discloses an o-amino aromatic amide derivative as well as a preparation method and application thereof. The o-amino aromatic amide derivative is a compound with a structural general formula I, II and III or a pharmaceutically acceptable salt

Visible light-promoted copper catalyzed regioselective acetamidation of terminal alkynes by arylamines

Herein, we describe a copper photoredox catalyzed synthesis of acetamide via regioselective C-N coupling of arylamines with terminal alkynes using molecular oxygen (O2) as an oxidant at room temperature under visible light irradiation (47 examples). Unique simultaneous formation of both amide and ester functionalities occurs via intramolecular cyclization in a single-step reaction in the case of anthranilic acids using inexpensive copper as a catalyst and eco-friendly O2 as an oxidant and reagent. Different substrates undergo different reaction pathways to generate similar acetamide products, as evidenced by 18O2 labelling experiments. The current protocol was also applied for the rapid, few step preparation of biologically active inhibitors (BACE-1 and PDE4). This process can be readily scaled up to a gram scale, and calculations of green metrics suggest the economic feasibility and eco-friendly nature of the current photoredox approach.

Synthesis of Aryl Ketoamides via Aryne Insertion into Imides

An insertion of arenes into both imides and anhydrides via reactive aryne intermediates is presented. The reaction is performed under exceptionally mild conditions, and the corresponding ketoamide products are amenable to derivatization to deliver a variety of synthetically useful motifs such as quinolones, indoles, and ketoanilines.

Synthesis of some new glutamine linked 2,3-disubstituted quinazolinone derivatives as potent antimicrobial and antioxidant agents

A series of novel glutamine linked 2,3-disubstituted quinazolinone conjugates was synthesized from methyl anthranilate and different substituted acids and acid chlorides. The compounds 5a-l were prepared in good yields. All compounds were screened for their antibacterial activity against Gram-positive and Gram-negative bacteria and for antifungal activity against Candida albicans and Aspergillus flavus using paper disk diffusion technique. The minimum inhibitory concentrations of the compounds were also determined by agar streak dilution method. The compound 5b was found to exhibit the most potent in vitro anti-microbial activity. When tested for their antioxidant activity, compounds 5i and 5l showed potent radical scavenging activity, while compound 5g had moderate effect against 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, nitric oxide, and superoxide radical scavenging assays. These results suggest that, the three quinazolinone analogs (5g, 5i, and 5l) could be considered as useful templates for future development to obtain more potent antioxidant agents.

Solution-phase combinatorial synthesis of 4-hydroxyquinolin-2(1H)-ones

Ion-exchange resins catalyse an intramolecular Claisen-type condensation leading to the title compounds, and also serve to purify the products.

Effect of plasma protein binding-on in vivo activity and brain penetration of glycine/NMDA receptor antagonists

A major issue in designing drugs as antagonists at the glycine site of the NMDA receptor has been to achieve good in vivo activity. A series of 4- hydroxyquinolone glycine antagonists was found to be active in the DBA/2 mouse anticonvulsant assay, but improvements in in vitro affinity were not mirrored by corresponding increases in anticonvulsant activity. Here we show that binding of the compounds to plasma protein limits their brain penetration. Relative binding to the major plasma protein, albumin, was measured in two different ways: by a radioligand binding experiment or using an HPLC assay, for a wide structural range of glycine/NMDA site ligands. These measures of plasma protein binding correlate well (r = 0.84), and the HPLC assay has been used extensively to quantify plasma protein binding. For the 4-hydroxyquinolone series, binding to plasma protein correlates (r = 0.92) with log P (octanol/pH 7.4 buffer) over a range of log P values from 0 to 5. The anticonvulsant activity increases with in vitro affinity, but the slope of a plot of pED50 versus pIC50 is low (0.40); taking plasma protein binding into account in this plot increases the slope to 0.60. This shows that binding to albumin in plasma reduces the amount of compound free to diffuse across the blood-brain barrier. Further evidence comes from three other experiments: (a) Direct measurements of brain/blood ratios for three compounds (2, 16, 26) show the ratio decreases with increasing log P. (b) Warfarin, which compotes for albumin binding sites dose-dependently, decreased the ED50 of 26 for protection against seizures induced by NMDLA. (c) Direct measurements of brain penetration using an in situ brain perfusion model in rat to measure the amount of drug crossing the blood-brain barrier showed that compounds 2, 26, and 32 penetrate the brain well in the absence of plasma protein, but this is greatly reduced when the drug is delivered in plasma. In the 4-hydroxyquinolones glycine site binding affinity increases with lipophilicity of the 3-substituent up to a maximum at a log P around 3, then does not improve further. When combined with increasing protein binding, this gives a parabolic relationship between predicted in vivo activity and log P, with a maximum log P value of 2.39. Finally, the plasma protein binding studies have been extended to other series of glycine site antagonists, and it is shown that for a given log P these have similar protein binding to the 4-hydroxyquinolones, except for compounds that are not acidic. The results have implications for the design of novel glycine site antagonists, and it is suggested that it is necessary to either keep log P low or pK(a) high to obtain good central nervous system activity.

Cyclization of N-acylanthranilic acids with Vilsmeier reagents. Chemical and structural studies

Vilsmeier reagents, generated from e.g. N,N-dimethylformamide and oxalyl chloride, reacts with N-acetylanthranilic acid to produce the 2-(2'-dimethylamino)ethenyl-4H-3,1-benzoxazin-4-one 13a. N-phenylacetylanthranilic acid similarly gave 2-(2'-dimethyl-am

Synthesis of Coumarins and Quinolones by Intramolecular Aldol Condensation Reactions of Titanium Enediolates

Low-valent titanium prepared by the reduction of TiCl3 with zinc dust oxidatively adds to α-ketoamides or α-ketoesters with the formation of the corresponding titanium enediolates.These 1,2-difunctional nucleophiles, which have hardly been used in organic

4-HYDROXY-2-QUINOLONES. 2. SIMPLE SYNTHESIS OF ARBORICINE

Acylation of methyl N-methylanthranilate with phenylacetyl chloride with subsequent intramolecular cyclization of the resulting anilide was used to synthesize 1-methyl-3-phenyl-4-hydroxy-2-quinolone (abroricine).

Synthesis and X-ray crystallographic analysis of quinazolinone cholecystokinin/gastrin receptor ligands

Compounds exemplified by 2-[2-(5-bromo-1H-indol-3-yl)ethyl]-3-[3-(1- methylethoxy)phenyl]-4(3H)-quinazolinone (3, IC50 = 0.0093 μM using mouse brain membranes) represent a structurally novel series of non-peptide cholecystokinin B receptor ligands. Since asperlicin, a selective CCK-A receptor antagonist, may be regarded as a conformationally constrained 2- substituted-3-phenyl-4(3H)-quinazolinone, the progenitor of compound 3 (compound 2, 2-[2-(1H-indol-3-yl)ethyl]-3-phenyl-4(3H)-quinazolinone) might therefore represent a conformationally flexible pharmacophore of the natural product. To probe possible conformational preferences for this class of receptor ligands, in particular the spatial relationship between the indole and quinazolinone rings, we prepared a series of analogues with methyl substituents on the ethylene bridge as well as congeners with different linkers. The X-ray crystal structure conformation for compound 22 (2-[2-(1H- indol-3-yl)ethyl]-3-]-3-(1-methylethoxy)phenyl]-4(3H)-quinazolinone, IC50 = 0.026 μM) is extended with the two heteroaromatic rings adopting an antiperiplanar arrangement around the central σ bond of the ethane linker, whereas the solid-state conformation for a less active analogue 19 (2-[2-(1H- indol-3-yl)-1-methylethyl]-3-[3-(1-methylethoxyphenyl]-4(3H)-quinazolinone, IC50 = 9.1 μM) is folded with the two heteroaromatic systems adopting a synclinal orientation. However, MM2 force field calculations (MacroModel, v 3.0) suggest that the energy difference between the folded and extended conformation is small. Thus, other factors such as unfavorable steric interactions may account for the difference in receptor affinity. For derivatives with one to three methylene units separating the indole and quinazolinone rings, maximal receptor binding activity was found when the distance separating the two heteroaromatic systems is defined by an ethyl group. Introducing unsaturation into the ethylene bridge of compound 3 limited the conformational flexibility of the molecule and decreased its receptor affinity greater than 2 orders of magnitude.