- A metal-free approach for in situ regioselective synthesis of isoxazoles via 1,3 dipolar cycloaddition reaction of nitrile oxide with propargyl bromide
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Herein, we report a multi-component reaction (MCRs) to synthesise a range of 3-phenyl-5-(bromomethyl)isoxazoles analogues using DMF/water mixture as solvent, providing desired products in good to excellent yields. The reaction efficiently involves the 1,3-dipolar cycloaddition reaction between propargyl bromide and in situ-generated α-chloro aldoximes. The protocol proceeded well under mild metal-free conditions and showed a tolerance for a wide range of substituents. Graphical abstract: [Figure not available: see fulltext.]
- Aleti, Rajeshwar Reddy,Cherukupalli, Srinivasulu,Dhawan, Sanjeev,Girase, Pankaj S.,Karpoormath, Rajshekhar,Kumar, Vishal,Mohite, Sachin
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- Product selectivity of thermal Buchner reaction of methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates with benzene, naphthalene and mesitylene, and ring-opening/closing reaction of products
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Methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates were synthesized and the product selectivity of their thermal Buchner reaction with benzene, naphthalene and mesitylene was studied. The reaction of the isoxazolyl-substituted diazoacetates with benzene gave
- Serebryannikova, Anna V.,Galenko, Ekaterina E.,Novikov, Mikhail S.,Khlebnikov, Alexander F.
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- CBP/CATENIN SIGNALING PATHWAY INHIBITORS AND USES THEREOF
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Provided are compounds of formula (Ia), (Ib) and (IIa), and pharmaceutically acceptable salts thereof. Additionally provided are compositions and pharmaceutical compositions comprising the compounds, therapeutic methods using same for modulating (e.g., inhibiting) CREB binding protein (CBP)/β-catenin mediated signaling in treating a condition, disease or disorder (e.g., fibrosis, cancer, neurological conditions, metabolic disorders (e.g., diabetes, etc.), and skin conditions (dermatitis, psoriasis, scarring, alopecia, etc.) mediated by aberrant CBP/β -catenin signaling, and cosmetic methods for treating skin conditions (e.g., aging, etc.). Additionally provided are methods for enhancing vaccine efficacy using the compounds and compositions. Further provided are methods for efficiently synthesizing a clinical grade drug, comprising use, in a penultimate, or last reaction step under GMP conditions, of an intermediate 2-propynyl-compound to form a clinical grade isoxazole derivative (e.g., via 3+2 cycloaddition).
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Page/Page column 51
(2021/09/17)
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- Facile synthesis and docking studies of 7-hydroxyflavanone isoxazoles and acrylates as potential anti-microbial agents
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The present study is aimed to synthesize the novel 7-hydroxyflavanone derived compounds and to assess their biological activity. Two series of compounds such as 2-phenyl-7-((3-phenylisoxazol-5-yl)methoxy)chroman-4-ones (6a–h) and 4-oxo-2-phenylchroman-7-yl acrylates (8a–k) were synthesized from 7-hydroxyflavanone. All the compounds were subjected to anti-microbial activity and molecular docking studies. The results showed that the compounds 6e, 6g–h, 8h–i and 8k were exhibited most potent anti-microbial activity when compared with the standard drugs. Further, the docking studies revealed that the compounds 6a and 8h have the highest binding affinity score of sterol 14-α demethylase and DNA gyrase B respectively. This is the first report assigning unique synthesis of 7-hydroxyflavanone derivatives and their anti-microbial activity proved with in silico studies. Furthermore, the present study is useful for constructive research to synthesize novel compounds along with their biological activity. [Figure not available: see fulltext.].
- Asha Bhanu,China Raju,Jayavardhana Rao,Narasimha,Kesava Rao
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p. 217 - 228
(2019/11/28)
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- Synthesis of Isoxazolines and Isoxazoles via Metal-Free Desulfitative Cyclization
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A novel, one-pot reaction for the synthesis of isoxazolines and isoxazoles is developed via a cascade process under metal-free conditions. The approach involves the formation of intramolecular C-N and C-O bonds and intermolecular C-C bonds from aromatic alkenes or alkynes and N -hydroxysulfonamides using hypervalent iodine(VII) and iodine as the oxidant. Activation of C-H and C-C bonds/construction of C-O bonds/elimination of SO 2 /C-N bond formation is achieved in sequence in the reaction system.
- Cheng, Jiaxin,Yang, Ze,Li, Yuansheng,Xi, Yulan,Sun, Qiu,He, Ling
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p. 2385 - 2393
(2018/05/28)
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- Synthesis of Halomethyl Isoxazoles/Cyclic Nitrones via Cascade Sequence: 1,2-Halogen Radical Shift as a Key Link
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A novel iminoxyl radical-promoted dichotomous regioselective 5-exo-trig cyclization onto vinylic halogen/1,2-halogen radical shift sequence is developed for the synthesis of halomethyl isoxazoles/cyclic nitrones using β-halo-β,?- and ?-halo-?,?-unsaturated ketoximes as the substrates and PhI(OAc)2/TEMPO as the oxidation system. DFT calculations reveal that a halogen-bridged three-membered ring transition state is involved in the 1,2-Cl-/Br-atom shift, while the 1,2-I atom migration can be taken into account with an elimination/readdition mechanism. The migration ability was indicated to be ranked in the following order: I > Br > Cl.
- Chen, Hong-Lei,Wei, Dian,Zhang, Jian-Wu,Li, Cheng-Lin,Yu, Wei,Han, Bing
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supporting information
p. 2906 - 2910
(2018/05/28)
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- Lead Optimization Generates CYP11B1 Inhibitors of Pyridylmethyl Isoxazole Type with Improved Pharmacological Profile for the Treatment of Cushing's Disease
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Cushing's disease, characterized by elevated plasma cortisol levels, can be controlled by inhibition of 11β-hydroxylase (CYP11B1). The previously identified selective and potent CYP11B1 inhibitor 5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine Ref 7 (IC50= 2 nM) exhibited promutagenic potential as well as very low oral bioavailability in rats (F = 2%) and was therefore modified to overcome these drawbacks. Successful lead optimization resulted in similarly potent and selective 5-((5-methoxypyridin-3-yl)methyl)-3-phenylisoxazole 25 (IC50 = 2 nM, 14-fold selectivity over CYP11B2), exhibiting a superior pharmacological profile with no mutagenic potential. Furthermore, compound 25 inhibited rat CYP11B1 (IC50 = 2 μM) and showed a high oral bioavailability (F = 50%) and sufficient plasma concentrations in rats, providing an excellent starting point for a proof-of-principle study.
- Emmerich, Juliette,Van Koppen, Chris J.,Burkhart, Jens L.,Hu, Qingzhong,Siebenbürger, Lorenz,Boerger, Carsten,Scheuer, Claudia,Laschke, Matthias W.,Menger, Michael D.,Hartmann, Rolf W.
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supporting information
p. 5086 - 5098
(2017/06/28)
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- Synthesis and in vitro biological evaluation of novel coumarin derivatives containing isoxazole moieties on melanin synthesis in B16 cells and inhibition on bacteria
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A novel series of coumarin derivatives 6a–o, bearing isoxazole moieties were designed and synthesized. After that, they were evaluated for melanin synthesis in murine B16 cells and inhibitory effect on the growth of CA (Candida albicans), EC (Escherichia coli), SA (Staphylococcus aureus). It was found that eleven compounds (6b–f, 6j–o) showed a better activity on melanin synthesis than positive control (8-MOP). Among them, compounds 6d (242%) and 6f (390%), with nearly 1.6 and 2.6-fold potency compared with 8-MOP (149%) respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo. Seven halogen substituted compounds exhibited moderate antimicrobial activity against CA. It is interesting that 6e–f and 6l–m, which had two halogens on the benzene showed a comparable activity with Amphotericin B against CA. The evaluation of melanin synthesis in B16 cells and inhibitory effect on bacteria of above structurally diverse derivatives had also led to an outline of structure-activity relationship.
- Pang, Guang Xian,Niu, Chao,Mamat, Nuramina,Aisa, Haji Akber
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p. 2674 - 2677
(2017/05/29)
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- Synthesis and bioactivity of novel isoxazole chalcone derivatives on tyrosinase and melanin synthesis in murine B16 cells for the treatment of vitiligo
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A new series of chalcone derivatives 1–18, bearing isoxazole moieties were designed and synthesized, and biologically evaluated for their activity on mushroom tyrosinase and melanin synthesis in murine B16 cells. The result indicated that most of prepared compounds 1–18 showed potent activating effect on tyrosinase, especially for 1–2, 4, 6–7, 9 and 15. Among them, compounds 2, 4 and 9 demonstrated the best activity with EC50?=?1.3, 2.5 and 3.0?μmol·L?1respectively, much better than the positive control 8-methoxypsoralan (8-MOP, EC50?=?14.8?μmol·L?1); In B16 cells, all the tested compounds exhibited a stronger activity on melanogenesis than 8-MOP (with the value of 115%). It was interesting that derivatives substituted with halogen (1, 2, 4, 5, 7, 9) were generally more potent. Compounds 2 (463%) and 18 (438%) with 3 and 4-fold potency compared with 8-MOP respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo.
- Niu, Chao,Yin, Li,Nie, Li Fei,Dou, Jun,Zhao, Jiang Yu,Li, Gen,Aisa, Haji Akber
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p. 5440 - 5448
(2016/10/24)
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- TRIAZOLOPYRIDINE AND TRIAZOLOPYRIMIDINE INHIBITORS OF MYELOPEROXIDASE
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The present invention provides compounds of Formula (I): wherein A and R1 are each as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.
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Paragraph 00230
(2016/06/01)
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- Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents
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Secretory phospholipase A2 (sPLA2) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a–10o) is synthesized and evaluated for their sPLA2 inhibitory activities. All compounds (10a–10o) showed significant sPLA2 inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 10o showed potent sPLA2 inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 10o showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a–10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA2-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies.
- Pedada, Srinivasa Rao,Yarla, Nagendra Sastry,Tambade, Pawan J.,Dhananjaya, Bhadrapura Lakkappa,Bishayee, Anupam,Arunasree, Kalle M.,Philip, Gundala Harold,Dharmapuri, Gangappa,Aliev, Gjumrach,Putta, Swathi,Rangaiah, Gururaja
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p. 289 - 297
(2018/04/19)
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- Safe and scaleable oxidation of benzaldoximes to benzohydroximinoyl chlorides
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Benzohydroximinoyl chlorides are useful precursors to nitrile oxides used in the preparation of various heterocycles via 1,3-dipolar cycloadditions. These intermediates are typically accessed by oxidation of aldoximes using N-chlorosuccinimide. This simpl
- Hansen, Eric C.,Levent, Mahmut,Connolly, Terrence J.
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scheme or table
p. 574 - 578
(2011/07/08)
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- Design, synthesis, and herbicidal activities of novel 2-cyanoacrylates containing isoxazole moieties
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A series of novel 2-cyanoacrylates containing an isoxazole moiety were designed and synthesized. Their structures were characterized by 1H NMR and elemental analysis (or high-resolution mass spectrometry). Their herbicidal activities against four species were evaluated, and the results indicated that some of the title compounds showed excellent herbicidal activities against rape and amaranth pigweed in postemergence treatment even at a dose of 75 g/ha.
- Liu, Yuxiu,Cui, Zhipeng,Liu, Bin,Cai, Baoli,Li, Yonghong,Wang, Qingmin
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experimental part
p. 2685 - 2689
(2011/07/07)
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- Synthesis of 5-bromomethylisoxazoles and their reactions with secondary amines
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Treating R-3-chloro-4-bromo-2-buten-1-ones with hydroxylamine hydrochloride afforded 3-alkyl(aryl, furyl)-5-bromomethylisoxazoles. By reaction of the latter with secondary amines new previously unknown aminoisoxazoles were synthesized. 2005 Pleiades Publi
- Aliev
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p. 1192 - 1195
(2007/10/03)
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- Generation of Nitrile Oxides via O-Tributylstannyl Aldoximes; Application to the Synthesis of Isoxazolines and Isoxazoles
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Nitrile oxides were generated readily by the reaction of aldoximes 1, with tert-butyl hypochlorite and bis(tributyltin) oxide.The reaction proceeded efficiently under mild conditions, in which O-stannylated aldoximes 2 are thought to be key intermediates.This reaction system was applicable to the one-pot syntheses of isoxazole derivatives 4 and 5 in the presence of dipolarophiles via a cycloaddition.
- Moriya, Osamu,Takenaka, Hideo,Iyoda, Masaichi,Urata, Yoshikiyo,Endo, Takeshi
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p. 413 - 418
(2007/10/02)
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- Synthesis of Isoxazolines and Isoxazoles via Generation of Nitrile Oxides from O-Stannyl Aldoximes
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The reactions of O-tributylstannyl aldoximes and active halogen compounds such as tert-butyl hypochlorite or N-bromosuccinimide, whereby nitrile oxides are generated effectively, are applied to the preparations of isoxazolines and isoxazoles via d
- Moriya, Osamu,Takenaka, Hideo,Urata, Yoshikiyo,Endo, Takeshi
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p. 1671 - 1672
(2007/10/02)
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- Antibacterial monic acid derivatives
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A compound of the formula (I) STR1 wherein R is a group STR2 R1 is hydrogen, phenyl, C1-20 alkyl, C2-8 alkenyl or C2-8 alkynyl each of which may optionally be substituted; or C3-7 cycloalkyl, X is a divalent group --Y--C=C--, and Y is oxygen or sulphur, have antibacterial and/or antimycoplasmal activity.
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- Fungicidal 3-phenyl-5-(substituted methyl) isoxaxoles
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A class of isoxazoles having a phenyl or substituted-phenyl group at the 3-position and a substituted-methyl group at the 5-position are useful for the control of fungal foliar phytopathogens.
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