5023-12-1

Usage

Uses

Used in Pharmaceutical Industry:
6-METHOXY-2H-BENZO[B][1,4]OXAZIN-3(4H)-ONE is used as a pharmaceutical compound for its potential role in the development of new drugs and medications. Its unique molecular structure and properties make it an intriguing target for further research and potential applications in various therapeutic areas.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, 6-METHOXY-2H-BENZO[B][1,4]OXAZIN-3(4H)-ONE serves as a valuable research tool for understanding its biological activities and exploring its potential as a lead compound in drug discovery. Its heterocyclic nature and specific functional groups may offer insights into novel mechanisms of action and therapeutic targets.
Used in Drug Design and Optimization:
6-METHOXY-2H-BENZO[B][1,4]OXAZIN-3(4H)-ONE is utilized in drug design and optimization processes to create structurally related analogs with improved pharmacological properties. By modifying its molecular structure, researchers can optimize its potency, selectivity, and pharmacokinetic profile, leading to the development of more effective and safer drugs.
Used in Biological Assays and Screening:
In biological assays and high-throughput screening, 6-METHOXY-2H-BENZO[B][1,4]OXAZIN-3(4H)-ONE is employed as a test compound to evaluate its interactions with various biological targets, such as enzymes, receptors, and ion channels. This information is crucial for understanding its mechanism of action and potential therapeutic applications.
Used in Chemical Synthesis:
6-METHOXY-2H-BENZO[B][1,4]OXAZIN-3(4H)-ONE is also used as a starting material or intermediate in the synthesis of other related compounds with potential applications in various industries, including pharmaceuticals, agrochemicals, and materials science. Its unique structure and reactivity make it a valuable building block for the development of novel molecules with diverse properties and functions.

InChI:InChI=1/C9H9NO3/c1-12-6-2-3-8-7(4-6)10-9(11)5-13-8/h2-4H,5H2,1H3,(H,10,11)

Upstream product

• 6238-93-3 2-(2-chloro-acetylamino)-4-methoxy-phenol 
• 53412-38-7 6-hydroxy-3,4-dihydro-2H-1,4-benzoxazin-3-one 
• 77-78-1 dimethyl sulfate 
• 69884-06-6 4-hydroxy-6-methoxy-(2H)-1,4-benzoxazin-3(4H)-one 
• 20734-76-3 2-amino-4-methoxyphenol 
• 79-04-9 chloroacetyl chloride 
• 33252-96-9 4-acetoxy-(2H)-1,4-benzoxazin-3(4H)-one 
• 89441-85-0 6-acetoxy-2H-1,4-benzoxazin-3(4H)-one 
• 771-26-6 4-hydroxy-2H-1,4-benzoxazin-3-one 
• 598-42-5 glycolamide 
• 36404-30-5 3,4-dichloroanisole 
• 67-56-1 methanol 
• 1002464-45-0 2-(4-methoxy-2-nitrophenoxy)acetonitrile 
• 109364-95-6 ethyl 2-[4-methoxy-2-nitrophenoxy]acetate 

Downstream Products

• 62490-80-6 2-benzylidene-6-methoxy-4H-benzo[1,4]oxazin-3-one 
• 6239-12-9 [2-(3,4-Dichloro-benzoylamino)-4-methoxy-phenoxy]-acetic acid 
• 62490-86-2 2-benzylidene-4-(3-dimethylamino-propyl)-6-methoxy-4H-benzo[1,4]oxazin-3-one 
• 26438-50-6 4-ethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-ol 
• 53412-38-7 6-hydroxy-3,4-dihydro-2H-1,4-benzoxazin-3-one 
• 26021-57-8 3,4-dihydro-6-hydroxy-1,4(2H)-benzoxazine 
• 58960-11-5 6-methoxy-3,4-dihydro-2H-benzo[1,4]oxazine 

Relevant academic research and scientific papers

OXAZINE-BASED FLUOROPHORE COMPOUNDS FOR NERVE-SPECIFIC IMAGING

This invention concerns novel oxazine-based fluorophore compounds useful in invivo nerve imaging, as well as compositions comprising them and methods for their use.

Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists

The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.

Synthesis, docking, 3-D-qsar, and biological assays of novel indole derivatives targeting serotonin transporter, dopamine D2 receptor, and mao-a enzyme: In the pursuit for potential multitarget directed ligands

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a-o) and (2-{4-[3-(1H-3-indolyl) -propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a-l) were synthesized and evaluated as novel multitarget ligands towards dopamine D2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).

Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core

With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 μM and 20.2 ± 0.9 μM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.

Design, synthesis and characterization of potent microtubule inhibitors with dual anti-proliferative and anti-angiogenic activities

Microtubule has been an important target for anticancer drug development. Here we report the discovery and characterization of a series of fused 4-aryl-4H-chromene-based derivatives as highly potent microtubule inhibitors. Among a total of 37 derivatives synthesized, 23 exhibited strong in vitro anti-proliferative activities against A375 human melanoma cells. The relationship between the biological activities of these microtubule inhibitors and their chemical structure variations was analyzed. Studies of compounds 27a, 19a and 9a in parallel with colchicine as the positive control compound in a panel of biological assays revealed that these compounds blocked cell cycle progression, increased apoptosis, and inhibited HUVEC capillary tube formation at low nanomolar concentrations. The most potent compound 27a was also tested in eight additional cancer cell lines besides A375 cells and two non-cancer cells and showed potent and selective activity on these cancer cells. To understand the molecular and structure mechanism of action of these compounds, tubulin polymerization and molecular docking studies were carried out for 27a as the representative. The results were consistent with the mechanism by which 27a interacts with the colchicine binding site on tubulin and disrupts tubulin polymerization. With potent dual actions of microtubule destabilization and vascular disruption described above, this small molecule can serve as a valuable research probe of the function and role of microtubules in human diseases and promising lead for developing new therapeutic agents.

Synthesis technology of 1,4-benzoxazinone compound

The invention relates to a synthesis technology of benzoxazinone compounds represented by formula I. The technology is characterized in that a dichlorobenzene derivative represented by formula II reacts with ethanolamide represented by formula III in the presence of a catalyst and an inorganic alkali to obtain the compound of formula I. R in the formula I and the formula II is selected from hydrogen, an amino group, a nitro group, a C1-6 alkyl group, a C1-6 alkoxy group and a hydroxyl group. The technology is a one-pot reaction method, realizes one-step direct cyclization, and has the advantages of simple reaction conditions, convenience in treatment, safe and highly-effective process, and high yield.

Synthetic technology for preparing 1,4-benzoxazinone through microwave process

The invention relates to a preparation method for a benzoxazine compound. The method comprises the following steps: adding the compound shown as formula II, methyl alcohol and catalyst into a reactor; reacting under the existence of catalyst and alkali; and performing post-processing after ending the reaction, thereby acquiring the compound shown as formula I. In the formula, R group is selected from hydrogen, amino, nitro, C1-C6 alkyl, C1-C6 alkoxy and hydroxy; alkyl is selected from methyl, ethyl and isopropyl; alkoxy is selected from methoxy group, ethyoxyl and isopropoxy. The method is low in cost of raw materials, is safe and reliable, is completed under normal temperature and normal pressure and is simple in process.

Efficient synthesis of benzene-fused 6/7-membered amides: Via Xphos Pd G2 catalyzed intramolecular C-N bond formation

An efficient approach for benzene-fused 6/7-membered amides via intramolecular amidation of aryl chlorides catalyzed by a Buchwald-Hartwig second generation Pd catalyst (Xphos Pd G2) has been successfully developed. This catalyst system allows the primary amides which have only modest nucleophilicity to be coupled successfully even with electron rich aryl chlorides in short reaction time. The intramolecular amidation reaction also has good chemoselectivity and excellent functional group compatibility.

Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction

We have synthesized bioactive 1,4-disubstituted 1,2,3-triazole analogues containing 2H-1,4-benzoxazin-3-(4H)-one derivatives via 1,3-dipolar cycloaddition in the presence of CuI. All the reactions proceeded smoothly and afforded its desired products in excellent yields. Among these analogues, 3y exhibited a better cytotoxic effect on human hepatocellular carcinoma (HCC) Hep 3B cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with Sorafenib, a targeted therapy for advanced HCC. 3y also induced stronger apoptosis and autophagy. Addition of curcumin enhanced 3y-induced cytotoxicity by further induction of autophagy. Using gene expression signatures of 3y to query Connectivity Map, a glycogen synthase kinase-3 inhibitor (AR-A014418) was predicted to display similar molecular action of 3y. Experiments further demonstrate that AR-A014418 acted like 3y, and vice versa. Overall, our data suggest the chemotherapeutic potential of 3y on HCC.

BICYCLIC HETEROCYCLIC DERIVATIVES AS BROMODOMAIN INHIBITORS

The present disclosure provides bicyclic heterocyclic derivatives of formula (I), which may be therapeutically useful, more particularly as bromodomain inhibitors; (I), in which R1, R2, R3, R4, L1, L2, Cy1, Cy2, X, n, and dotted line have the same meaning given in the specification, and pharmaceutically acceptable salts or pharmaceutically acceptable stereoisomers thereof that are useful in the treatment and prevention of diseases or disorders, in particular their use in diseases or disorders associated as bromodomain inhibitors. The present disclosure also provides preparation of compounds and pharmaceutical formulations comprising at least one of bicyclic heterocyclic derivatives of formula (I), together with a pharmaceutically acceptable carrier, diluent, or excipient.