89684-58-2Relevant academic research and scientific papers
SMYD2 INHIBITORS
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Paragraph 0113, (2016/02/20)
The present disclosure generally relates to compounds having cellular anti-proliferative activities, and more particularly relates to compounds which inhibit the activity of human SMYD2, a SET and MYND domain-containing protein lysine methyltransferase.
Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2
Sweis, Ramzi F.,Wang, Zhi,Algire, Mikkel,Arrowsmith, Cheryl H.,Brown, Peter J.,Chiang, Gary G.,Guo, Jun,Jakob, Clarissa G.,Kennedy, Steven,Li, Fengling,Maag, David,Shaw, Bailin,Soni, Nirupama B.,Vedadi, Masoud,Pappano, William N.
supporting information, p. 695 - 700 (2015/06/30)
A lack of useful small molecule tools has precluded thorough interrogation of the biological function of SMYD2, a lysine methyltransferase with known tumor-suppressor substrates. Systematic exploration of the structure-activity relationships of a previous
Total synthesis of (-)-platensimycin by advancing oxocarbenium- and iminium-mediated catalytic methods
Eey, Stanley T.-C.,Lear, Martin J.
, p. 11556 - 11573 (2015/01/16)
(-)-Platensimycin is a potent inhibitor of fatty acid synthase that holds promise in the treatment of metabolic disorders (e.g., diabetes and "fatty liver") and pathogenic infections (e.g., those caused by drug-resistant bacteria). Herein, we describe its total synthesis through a four-step preparation of the aromatic amine fragment and an improved stereocontrolled assembly of the ketolide fragment, (-)-platensic acid. Key synthetic advances include 1) a modified Lieben haloform reaction to directly convert an aryl methyl ketone into its methyl ester within 30 seconds, 2) an experimentally improved dialkylation protocol to form platensic acid, 3) a sterically controlled chemo- and diastereoselective organocatalytic conjugate reduction of a spiro-cyclized cyclohexadienone by using the trifluoroacetic acid salt of α-amino di-tert-butyl malonate, 4) a tetrabutylammonium fluoride promoted spiro-alkylative para dearomatization of a free phenol to assemble the cagelike ketolide core with the moderate leaving-group ability of an early tosylate intermediate, and 5) a bismuth(III)-catalyzed Friedel-Crafts cyclization of a free lactol, with LiClO4 as an additive to liberate a more active oxocarbenium perchlorate species and suppress the Lewis basicity of the sulfonyloxy group. The longest linear sequence is 21 steps with an overall yield of 3.8% from commercially available eugenol. Relay tactics: The stereocontrolled assembly of the potent antibiotic (-)-platensimycin in 21 steps and 3.8% yield from eugenol is described (see scheme; TBAF: tetrabutylammonium fluoride; Ts: toluene-4-sulfonyl). Highlights are 1) a rapid oxidative esterification of an acyl aromatic, 2) a reliable dialkylation protocol to form platensic acid, 3) a π-facial conjugate reduction of a dienone, 4) a TBAF-promoted alkylative dearomatization of a free phenol, and 5) a Friedel-Crafts closure of a free lactol.
BENZOXAZINONE DERIVATIVES ACTING AS BETA2-ADRENORECEPTOR AGONIST FOR THE TREATMENT OF RESPIRATORY DISORDERS
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Page/Page column 35, (2010/01/12)
The present invention provides a compound of formula (I), wherein W, R1, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
AMINE DERIVATIVES AND THEIR USE IN BETA-2-ADRENORECEPTOR MEDIATED DISEASES
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Page/Page column 83-84, (2008/12/06)
The present invention provides compounds of formula (I), wherein k, Ar, R2, R3, R4, R5, R4', R5', R6, R7, A, D, m and E are as defined in the specification, processes
Electrochemically induced cascade reaction for the assembly of libraries of biologically relevant 1,4-benzoxazine derivatives
Xu, Daiwang,Chiaroni, Angele,Fleury, Maurice-Bernard,Largeron, Martine
, p. 6374 - 6381 (2007/10/03)
The scope and mechanism of an electrochemically induced cascade reaction, which leads to highly substituted 1,4-benzoxazine derivatives, have been explored through the variation of the structure of the o-azaquinone mediator. This reaction sequence, wherein both cycloaddition partners are generated in situ, at room temperature, under metal-free conditions, allows the regiospecific inverse-electron-demand Diels-Alder (IEDDA) reaction of an o-azaquinone heterodiene and a secondary alkylenamine dienophile, two chemically nonaccessible unstable entities. The cascade reaction was found to be general with electron-poor o-azaquinone entities generated from substituted 2-aminoresorcinol substrates. In the case of o-aminophenol derivatives which lack the 2-hydroxyl group, the generated o-azaquinone species failed to catalyze the oxidation of the amine to the corresponding imine, precursor of the enamine dienophile, because the absence of an intramolecular hydrogen bond at the origin of a highly reactive Schiff base cyclic transition state. To overcome this problem, a tandem oxidation-IEDDA reaction, in which the o-azaquinone is generated in the presence of a preformed enamine, has been developed as an alternative. These one-pot methodologies, which offer the opportunity to introduce variations in both cycloaddition partners, should be particularly useful for the development of libraries of biologically relevant 1,4-benzoxazine derivatives.
Reaction of Cerium(IV) Ammonium Nitrate with Aralkyl and Aromatic Ketones
Chawla, H. Mohindra,Mittal, Ram S.,Johny, C. J.
, p. 992 - 993 (2007/10/02)
Fluoren-9-one on treatment with cerium(IV) ammonium nitrate (CAN) yields five compounds which have been identified as 3-nitro-; 2-nitro; 1,8-dinitro; 2,7-dinitro; and 2,7-dinitrofluoren-9-ones.Acetophenone on treatment with CAN, yields only benzoic acid while 2,4-dihydroxyacetophenone on similar treatment yields three compounds which have been identified as 2,4-dihydroxy-5-nitro; 2,4-dihydroxy-3-nitro; and 2,4-dihydroxy-3,5-dinitro-acetophenones.
