- Intramolecular cyclization of N-hydroxy-2-phenoxyacetamides and 3-phenoxypropanamides
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Abstract: A novel route for the preparation of 2H-1,4- benzoxazin-3(4H)one and 1,5 benzoxazepinones by intramolecular cyclization of N-hydroxy 2-phenoxyacetamide and N-hydroxy -3 phenoxypropanamide using PPA and Lewis acid has been discussed. Graphical abstract: [Figure not available: see fulltext. Caption: Preparation of 2H-1,4- benzoxazin-3(4H)one and 1,5 benzoxazepinones by electrophilic aromatic substitution from N-hydroxy 2-phenoxyacetamide and N-hydroxy -3 phenoxypropanamide and their acetyl and benzoyl derivatives using PPA and Lewis acids.]
- Dittakavi, Ramachandran,Madhavarao, Nagarajan,Mannam, Krishnamurthy,Nagalingam, Viswanath,Sreenivasulu, Reddymasu
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- Benzo six-membered nitrogen heterocyclic compound, preparation method and applications
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The present invention provides a benzo six-membered nitrogen heterocyclic compound, a preparation method and applications, wherein the benzo six-membered nitrogen heterocyclic compound has a structurerepresented by a formula I or formula II, and can effectively inhibit the bromine domain receptor and effectively inhibit the proliferation of cancer cells. Compared with the existing reported structure types, the compound of the present invention has different binding mode, has high inhibitory activity, can be used as a drug for treating cancer, cell proliferation disorders, inflammatory diseases, autoimmune diseases, septicemia and viral infections, and has good application prospects and high application value.
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Paragraph 0106-0107
(2019/10/01)
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- Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core
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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.
- Méndez-Rojas, Claudio,Quiroz, Gabriel,Faúndez, Mario,Gallardo-Garrido, Carlos,Pessoa-Mahana, C. David,Chung, Hery,Gallardo-Toledo, Eduardo,Saitz-Barría, Claudio,Araya-Maturana, Ramiro,Kogan, Marcelo J.,Zú?iga-López, María C.,Iturriaga-Vásquez, Patricio,Valenzuela-Gutiérrez, Carla,Pessoa-Mahana, Hernán
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- New Approach to 1,4-Benzoxazin-3-ones by Electrochemical C?H Amination
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1,4-Benzoxazin-3-ones are important structural motifs in natural products and bioactive compounds. Usually, the synthesis of benzoxazinones requires transition-metal catalysts and pre-functionalized substrates such as aryl halides. However, the anodic C?H
- Wesenberg, Lars Julian,Herold, Sebastian,Shimizu, Akihiro,Yoshida, Jun-Ichi,Waldvogel, Siegfried R.
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supporting information
p. 12096 - 12099
(2017/09/13)
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- Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction
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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.
- Su, Chun-Li,Tseng, Chia-Ling,Ramesh, Chintakunta,Liu, Hsiao-Sheng,Huang, Chi-Ying F.,Yao, Ching-Fa
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- Potential antimicrobial agents from triazole-functionalized 2H-benzo[b][1,4]oxazin-3(4H)-ones
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A series of substituted triazole functionalized 2H-benzo[b][1,4]oxazin-3(4H)-ones were synthesized by employing click chemistry and further characterized based on 1H NMR, 13C NMR, IR and mass spectral studies. All the synthesized derivatives were screened for their in vitro antimicrobial activities. Further, molecular docking studies were accomplished to explore the binding interactions between 1,2,3-triazol-4-yl-2H-benzo[b][1,4]oxazin-3(4H)-one and the active site of Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCS). These docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9c, 9d and 9e were identified as promising antimicrobial leads.
- Bollu, Rajitha,Banu, Saleha,Bantu, Rajashaker,Reddy, A. Gopi,Nagarapu, Lingaiah,Sirisha,Kumar, C. Ganesh,Gunda, Shravan Kumar,Shaik, Kamal
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supporting information
p. 5158 - 5162
(2017/11/21)
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- Design and Synthesis of Novel Triazolyl Benzoxazine Derivatives and Evaluation of Their Antiproliferative and Antibacterial Activity
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A series of novel triazolyl benzoxazine derivatives have been synthesized via Cu(I)-catalyzed ‘Click’ cycloaddition. All of the compounds were fully characterized from their spectral data, and their antiproliferative activity was evaluated against three selected human cancer cell lines: cervical cancer cells (HeLa), colorectal adenocarcinoma (HT-29), and ovarian adenocarcinoma (SKOV-3). A few representative compounds have also been evaluated for their antibacterial potential against two bacterial strains Pseudomonas aeruginosa and Bacillus subtilis.
- Khan, Abdullah,Prasad, Suchita,Parmar, Virinder S.,Sharma, Sunil K.
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p. 1264 - 1275
(2016/07/29)
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- Development of small-molecule Trypanosoma brucei N-myristoyltransferase inhibitors: Discovery and optimisation of a novel binding mode
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The enzyme N-myristoyltransferase (NMT) from Trypanosoma brucei has been validated both chemically and biologically as a potential drug target for human African trypanosomiasis. We previously reported the development of some very potent compounds based around a pyrazole sulfonamide series, derived from a high-throughput screen. Herein we describe work around thiazolidinone and benzomorpholine scaffolds that were also identified in the screen. An X-ray crystal structure of the thiazolidinone hit in Leishmania major NMT showed the compound bound in the previously reported active site, utilising a novel binding mode. This provides potential for further optimisation. The benzomorpholinone was also found to bind in a similar region. Using an X-ray crystallography/structure-based design approach, the benzomorpholinone series was further optimised, increasing activity against T. brucei NMT by >1000-fold. A series of trypanocidal compounds were identified with suitable in vitro DMPK properties, including CNS exposure for further development. Further work is required to increase selectivity over the human NMT isoform and activity against T. brucei. HATs off to diversity! Screening a diverse library against Trypanosoma brucei N-myristoyltransferase (NMT) identified hits based on thiazolidinone and benzomorpholine scaffolds. X-ray crystallography of these compounds bound to Leishmania major NMT revealed novel active site binding conformations. Using the structural information, the benzomorpholine scaffold was optimised to a blood-brain barrier penetrant compound with activity against TbNMT of 0.002 μm.
- Spinks, Daniel,Smith, Victoria,Thompson, Stephen,Robinson, David A.,Luksch, Torsten,Smith, Alasdair,Torrie, Leah S.,McElroy, Stuart,Stojanovski, Laste,Norval, Suzanne,Collie, Iain T.,Hallyburton, Irene,Rao, Bhavya,Brand, Stephen,Brenk, Ruth,Frearson, Julie A.,Read, Kevin D.,Wyatt, Paul G.,Gilbert, Ian H.
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p. 1821 - 1836
(2015/11/10)
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- Identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives as potassium channel activators and anti-inflammatory agents
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The present study described the design, synthesis and identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives. Their biological activity was tested for KATP channel opener as antihypertensives, COX-1 and COX-2 activity. The results were compared with the activity of cromakalim, ibuprofen and celecoxib. The study aimed at exploring the influence of introduction of a benzoxazine substituent at position 6 of various derivatives of benzopyrans in order to improve biological activity. Several compounds were found to be equipotent or even more potent than cromakalim. Out of these nitro-substituted benzopyrans, nitro substitution at benzoxazino group possessed potent antihypertensive activity in the R/S isomers. With amino derivatives, activity remains constant when compared with standard cromakalim. Similarly, compounds 17b, 17c, 17e and 17h have exhibited around 40 % inhibition of COX-1 as compared to the inhibition of COX-2. Only two compounds 17g and 17i exhibited effective inhibition more than 50 % of COX-2 compared with the inhibition of COX-1 at a concentration of 0.3 mg/ml.
- Bano, Mohsina,Barot, Kuldipsinh P.,Jain, Shailesh V.,Ghate, Manjunath D.
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p. 3008 - 3020
(2015/03/18)
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- Microwave-assisted synthesis of benzo-[1,4]-oxazinones using MeO-PEG-OMe as solvent
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Efficient one-pot microwave-assisted synthesis of various benzo-[1,4]-oxazinones via Smiles rearrangement is described. Treatment of 2-chloroacetamide, substituted 2-chlorophenols and cesium carbonate in MeO-PEG-OMe (2,000) as solvent afforded the corresp
- Lim, Jae-Min,Gam, Gyunghee,Kim, Shin-Hyuong,Shin, Dong-Soo,Jang, Kiwan
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p. 468 - 472,5
(2020/08/31)
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- Exploring Left-Hand-Side substitutions in the benzoxazinone series of 4-amino-piperidine bacterial type IIa topoisomerase inhibitors
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An SAR survey at the C-6 benzoxazinone position of a novel scaffold which inhibits bacterial type IIa topoisomerase demonstrates that a range of small electron donating groups (EDG) and electron withdrawing groups (EWG) are tolerated for antibacterial activity. Cyano was identified as a preferred substituent that affords good antibacterial potency while minimizing hERG cardiac channel activity.
- Geng, Bolin,Comita-Prevoir, Janelle,Eyermann, Charles J.,Reck, Folkert,Fisher, Stewart
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scheme or table
p. 5432 - 5435
(2011/10/12)
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- A simple and facile route for the synthesis of 2H-1,4-benzoxazin-3-(4H)- ones via reductive cyclization of 2-(2-nitrophenoxy)acetonitrile adducts in the presence of Fe/acetic acid
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A simple route for the synthesis of 1,4-benzoxazin-3-(4H)-ones is described herein. This method involves the reductive cyclization of 2-(2-nitrophenoxy) acetonitrile adducts in the presence of Fe/acetic acid in good to excellent yields. This system was compatible with various other functional groups.
- Ramesh, Chintakunta,Raju, B. Rama,Kavala, Veerababurao,Kuo, Chun-Wei,Yao, Ching-Fa
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p. 1187 - 1192
(2011/03/22)
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- [Omim][BF4], a green and recyclable ionic liquid medium for the one-pot chemoselective synthesis of benzoxazinones
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An efficient procedure for the one-pot chemoselective synthesis of 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives from their corresponding o-aminophenols is developed using DBU in the ionic liquid [omim][BF4]. Upon completion of the reaction and separation of the product, the ionic liquid is recovered and successfully reused over nine recycles without any noticeable loss of performance.
- Sharifi, Ali,Barazandeh, Mehdi,Saeed Abaee,Mirzaei, Mojtaba
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experimental part
p. 1852 - 1855
(2010/09/07)
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- An efficient cascade synthesis of various 2H-1,4-benzoxazin-3-(4H)-ones from o-halophenols and 2-halo-amides catalyzed by CuI
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A novel and efficient one-pot cascade synthesis of 2H-1,4-benzoxazin-3-(4H) -ones has been developed through copper-catalyzed coupling of o-halophenols and 2-halo-amides. Various 2H-1,4-benzoxazin-3-(4H)-ones with diversity at three substituents on their
- Chen, Dingben,Shen, Guodong,Bao, Weiliang
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experimental part
p. 4067 - 4073
(2009/12/05)
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- Microwave-assisted one-pot synthesis of benzo[b][1,4]oxazin-3(4H)-ones via Smiles rearrangement
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An efficient method for the synthesis of benzo[b][1,4]oxazin-3(4H)-ones via Smiles rearrangement using a microwave-assisted one-pot, three-step reaction has been developed. Various benzo[b][1,4]oxazin-3(4H)-ones are obtained in good yields (55-86%) from t
- Zuo, Hua,Meng, Lijuan,Ghate, Manjunath,Hwang, Kyu-Hyeon,Kweon Cho, Yong,Chandrasekhar,Raji Reddy,Shin, Dong-Soo
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p. 3827 - 3830
(2008/09/21)
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- Pharmaceutical Compositions Comprising Nitrogen-Containing Fused Ring Coumpounds
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[Problems] The present invention provides pharmaceutical composition which is effective for the prophylaxis or treatment of pathology showing involvement of uric acid (hyperuricemia, gouty tophus, acute gout arthritis, chronic gout arthritis, gouty kidney, urolithiasis, renal function disorder, coronary arterial disease, ischemic heart disease and the like) and the like, and is superior in the time-course stability and dissolution property (disintegration property). [Solving Means] The pharmaceutical composition of the present invention is a pharmaceutical composition comprising a nitrogen-containing fused ring compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable additives, wherein the nitrogen-containing fused ring compound or a pharmaceutically acceptable salt thereof is not in contact with a basic additive: wherein each symbol is as described in the specification.
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- Production Method of Nitrogen-Containing Fused Ring Compounds
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[Problems] The present invention provides a superior production method and a superior purification method of compounds effective for the treatment or prophylaxis of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like. [Means] A compound represented by the following formula [2] or a pharmaceutically acceptable salt thereof can be produced by reacting a compound represented by the following formula [3] or a salt thereof with a compound represented by the following formula [4], a salt thereof or a reactive derivative thereof. Moreover, crystallization of a compound represented by the formula [2] can be performed with industrially superior workability, and high quality crystals of a compound represented by the formula [2] can be obtained. wherein each symbol is as defined in the description.
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Page/Page column 58
(2010/11/30)
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- A convenient synthesis of 3,4-dihydro-1,4-benzoxazin-2-ones
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3,4-Dihydro-1,4-benzoxazin-2-one was prepared for the first time by catalytic hydrogenation of 4-benzyl-3,4-dihydro-1,4-benzoxazin-2-one. A simple and efficient synthesis of 4-benzyl- and 4-alkyl-3,4-dihydro-1,4-benzoxazin-2-one derivatives from ethyl 2-(2-hydroxyphenylamino)acetate and aldehydes is described. Some considerations regarding the reactivity of 3,4-dihydro-1,4-benzoxazin-2-ones are given.
- Zidar, Nace,Kikelj, Danijel
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p. 5756 - 5761
(2008/09/21)
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- MONOCYCLIC AND BICYCLIC COMPOUNDS AND METHODS OF USE
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Compounds are provided that act as potent antagonists of the CCR1 receptor, and have in vivo anti-inflammatory activity. The compounds are generally monocyclic and bicyclic compounds and are useful in pharmaceutical compositions, methods for the treatment of CCR1-mediated diseases, and as controls in assays for the identification of competitive CCR1 antagonists.
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Page/Page column 77
(2010/11/26)
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- Nitrogen-containing fused ring compounds and use thereof
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A URAT1 activity inhibitor containing a nitrogen-containing fused ring compound represented by the following formula [1]: wherein each symbol is as defined in the description. The present invention is useful for the prophylaxis or treatment of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like.
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Page/Page column 95
(2010/11/25)
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- PHENOXIACETIC ACID DERIVATIVES
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The invention relates to certain 2-substituted phenoxyacetic acid derivatives of formula (I), in which the variables are as defined in the claims, useful in the treatment of diseases or conditions in which modulation of the CRTh2 receptor is beneficial, s
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Page/Page column 32
(2008/06/13)
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- Synthesis by microwave irradiation of a substituted benzoxazine parallel library with preferential relaxant activity for guinea pig trachealis
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An efficient, facile, and practical parallel combinatorial synthesis of substituted-benzoxazines under microwave irradiation was described. The procedure involved the use of a microwave oven especially designed for organic synthesis suitable for parallel synthesis of solution libraries. A demonstration 19-membered library of substituted N,N-dimethyl- and N-methyl-benzoxazine amide derivatives, structurally related to the potassium channel opener cromakalim, was generated by both conventional and microwave procedures, achieving a reduction from 7 h to 30-36 min in library generation time for the microwave approach. All the synthesized compounds were tested using the in vitro models of rat aorta and guinea pig trachea rings pre-contracted with phenylephrine and carbachol, respectively. All N,N-dimethyl amide derivatives showed a relaxant activity higher on guinea pig trachea rings than on rat aorta rings.
- Caliendo, Giuseppe,Perissutti, Elisa,Santagada, Vincenzo,Fiorino, Ferdinando,Severino, Beatrice,Cirillo, Donatella,D'Emmanuele Di Villa Bianca, Roberta,Lippolis, Laura,Pinto, Aldo,Sorrentino, Raffaella
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p. 815 - 826
(2007/10/03)
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- Synthesis and vasorelaxant activity of new 1,4-benzoxazine derivatives potassium channel openers
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As part of a search for new potassium channel openers, the synthesis and vasorelaxant activity of new 1,4-benzoxazine derivatives derived from transformation of the benzopyran skeleton of cromakalim were described. Several new 1,4-benzoxazine derivatives were provided with significant vasorelaxant activity with an overall pharmacological behavior similar to CRK (1f, 1i, 2d, 2e, 2f and 2i).
- Caliendo, Giuseppe,Perissutti, Elisa,Santagada, Vincenzo,Fiorino, Ferdinando,Severino, Beatrice,Di Villa Bianca, Roberta d'Emmanuele,Lippolis, Laura,Pinto, Aldo,Sorrentino, Raffaella
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p. 2663 - 2669
(2007/10/03)
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- Fungicidal acrylate derivatives
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Compounds, useful as plant fungicides, having the formula (I): STR1 or a stereoisomer thereof, wherein A is CH or N, B is OCH3 or NHCH3, X is CH2, CH2 O, O or S, Y is R1 --C=C--R2 or R
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- Synthesis, biological activity and conformational study of 1,4- benzoxazine derivatives as potassium channel modulators
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With the aim of discovering new molecules with K+-channel activating properties, we have synthesized derivatives of cromakalim (CRK), an important molecule which shows specific affinity towards K+ channels, by replacing the benzopyrane ring of this reference compound with a 1,4-benzoxazine moiety. A different number of substituents showing a good discrimination between hydrophobic and electronic properties have been inserted at the 6-position of the 1,4-benzoxazine ring. We describe here the synthesis and discuss the solid state conformation of these new molecules. When tested on rat aorta ring precontracted with phenylephrine, two compounds (2c and 2d) showed a concentration-dependent relaxation similar to that measured for cromakalim but less potent than this reference drug.
- Caliendo, Giuseppe,Grieco, Paolo,Perissutti, Elisa,Santagada, Vincenzo,Santini, Antonello,Albrizio, Stefania,Fattorusso, Caterina,Pinto, Aldo,Sorrentino, Raffaella
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p. 957 - 967
(2007/10/03)
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- Potential Diuretics: Part I - Synthesis of Some Substituted 2,4-Dihydro-1-oxo/thioxotriazolobenzoxazines, Novel Diuretic Agents
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Several compounds (V) derived from 2,4-dihydro-1-oxobenzoxazine and some of their 1-thioxo analogues (VI) have been synthesized and evaluated for their diuretic activity in rats.Compound Vg is the most potent member of this series with 250percent urine output of the saline control at 1 mg/kg dose.The pattern of excretion of electrolytes is similar to that of the hydrochlorothiazide at the same dose.Furthermore, its diuretic activity is very much dose-dependent over a wide range of doses (1.0-32.0 mg/kg).
- Shridhar, D. R.,Jogibhukta, M.,Krishnan, V. S. H.,Joshi, P. P.,Naidu, M. U. R.,et al.
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p. 1279 - 1283
(2007/10/02)
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- Synthesis and pharmacological activity of 4 substituted 2,3 dihydro 1,4 benzoxazin 3 ones
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Some derivatives of 3 oxo 2,3 dihydro 1,4 benzoxazine substituted with aminoalkyl and hydroxyalkyl groups were prepared and their analgesic activity studied. This was weak for the amino, but very important for the propranediol derivatives. One of them, AN
- Thuillier,Laforest,Bessin,et al.
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