- Synthesis of some novel tricyclic α-aminoacid esters and potential bioactive compounds via 1,2-prototropy and 1,3-APT cascade reactions
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Some novel cyclic α-aminoacid esters and potential bioactive compounds were prepared via thermal 1,2-prototropy- and 1,3-APT oxime nitrone-1,3-dipolar cycloaddition cascades reactions. This substrate allows the influence of the new stereocentres on the cascade to be assessed with respect to the configuration of the nitrone that is generated and the facial selectivity of the subsequent cycloaddition.
- Dondas, H. Ali,Dondas, Naciye Yaktubay
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- Synthesis of some novel tricyclic α- amino acid esters and potential bioactive compounds via 1,2-prototropy and 1,3-APT cascade reactions
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Some novel cyclic α-aminoacid esters and potential bioactive compounds were prepared via thermal 1,2-prototropy- and 1,3-APT oxime nitrone-1,3-dipolar cycloaddition cascades reactions. This substrate allows the influence of the new stereocentres on the cascade to be assessed with respect to the configuration of the nitrone that is generated and the facial selectivity of the subsequent cycloaddition.
- Dondas, H. Ali,Dondas, Naciye Yaktubay
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- Synthesis of sterically encumbered 11β-aminoprogesterone derivatives and evaluation as 11β-hydroxysteroid dehydrogenase inhibitors and mineralocorticoid receptor antagonists
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11β-Hydroxyprogesterone is a well-known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2. It also activates the mineralocorticoid receptor (MR). Modulation of corticosteroid action by inhibition of 11βHSDs or blocking MR i
- Pandya, Keyur,Dietrich, David,Seibert, Julia,Vederas, John C.,Odermatt, Alex
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- Palladium-catalysed imidoylative spirocyclization of 3-(2-isocyanoethyl)indoles
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A palladium-catalysed construction of spiroindolines through dearomative spirocyclization of 3-(2-isocyanoethyl)indoles has been developed. 2′-Aryl-, vinyl-, and alkyl-substituted spiroindolines could be accessed under mild conditions with excellent functional group tolerance. C1-tethered oxindole- and indole-spiroindoline bisheterocycles were generated in high yieldsviaalkene/allene insertion and an imidoylative spirocyclization cascade. Additionally, a tandem dearomatization of two different indoles was realized withN-(2-bromobenzoyl)indoles as the electrophilic coupling partner of 3-(2-isocyanoethyl)indoles, affording polyindoline-spiroindoline bisheterocyclic scaffolds conveniently. Under the catalysis of Pd(OAc)2and a spinol-derived phosphoramidite ligand, chiral spiroindolines were successfully accessed with up to 95% yield and 85% ee.
- Tang, Shi,Ding, Shumin,Li, Dan,Li, Lianjie,Zhao, Haixia,Chai, Minxue,Wang, Jian
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supporting information
p. 10576 - 10579
(2021/10/19)
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- KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE
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Described herein are compounds having the following structure: formula (I) or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof. Also disclosed are compositions containing the compounds, methods of inhibiting activity of DYRKl A in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.
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Paragraph 0212
(2019/10/15)
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- Development of Kinase-Selective, Harmine-Based DYRK1A Inhibitors that Induce Pancreatic Human β-Cell Proliferation
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DYRK1A has been implicated as an important drug target in various therapeutic areas, including neurological disorders and oncology. DYRK1A has more recently been shown to be involved in pathways regulating human β-cell proliferation, thus making it a potential therapeutic target for both Type 1 and Type 2 diabetes. Our group, using a high-throughput phenotypic screen, identified harmine that is able to induce β-cell proliferation both in vitro and in vivo. Since harmine has suboptimal kinase selectivity, we sought to expand structure-activity relationships for harmine's DYRK1A activity, to enhance selectivity, while retaining human β-cell proliferation capability. We carried out the optimization of the 1-position of harmine and synthesized 15 harmine analogues. Six compounds showed excellent DYRK1A inhibition with IC50 in the range of 49.5-264 nM. Two compounds, 2-2 and 2-8, exhibited excellent human β-cell proliferation at doses of 3-30 μM, and compound 2-2 showed improved kinase selectivity as compared to harmine.
- Kumar, Kunal,Wang, Peng,Sanchez, Roberto,Swartz, Ethan A,Stewart, Andrew F.,Devita, Robert J.
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p. 7687 - 7699
(2018/09/22)
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- COMPOUNS, COMPOSITIONS AND METHODS OF USE
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Herein, compounds, compositions and methods for modulating inclusion formation and stress granules in cells related to the onset of neurodegenerative diseases, musculoskeletal diseases, cancer, ophthalmological diseases, and viral infections are described.
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Page/Page column 194; 195
(2018/07/29)
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- A method for synthesizing pyrroloquinoline quinone (by machine translation)
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The invention relates to a synthetic pyrroloquinoline quinone of the method, the method to pyruvic acid ethyl ester as the starting synthetic raw material, preparation pyrroloquinoline quinone. In the synthetic method of the present invention, compound 4 synthesis of compound 5 is the key step in the synthetic route, in the key step 5) in, the invention creative use of hexafluoro antimonate ion liquid, hexafluoro titanate ion liquid, six fluorine niobium acid salt ion liquid such as Lewis acid ionic liquid, the ionic liquid has the function of the reaction medium and the catalyst, thereby improving the response speed and the yield of this step. In addition, the invention preferably use the [BMIm] SbF6 Ionic liquid, [BMIm] SbF6 Ionic liquid and Sc (OTf)3 Can be formed of a higher catalytic activity [Sc (OTf)3 -x ] [SbF6 ], Can make the reaction efficiency is greatly improved, and the obtained reaction product in [BMIm] SbF6 The solubility of the ionic liquid in small, easily precipitated, so as to improve the reaction yield (can be up to 96%). (by machine translation)
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Paragraph 0029; 0040; 0043
(2018/08/28)
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- Compound as apoptosis protein inhibitor, and application thereof
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The present invention belongs to the field of medical chemistry, relates to a class of compounds of apoptosis protein inhibitors, and applications thereof, and particularly provides a compound represented by a formula I, or an isomer thereof, a pharmaceut
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Paragraph 0347; 0352; 0353; 0354
(2018/09/12)
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- Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate
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We have explored here the scope of the age-old diethyl malonate-based accesses to α-amino esters involving Knoevenagel condensations of diethyl malonate on aldehydes, reductions of the resulting alkylidenemalonates, the preparation of the corresponding α-hydroxyimino esters and their final reduction. This synthetic pathway turned out to be general although some unexpected limitations were encountered. The synthetic modifications of some of the intermediates - using Suzuki-Miyaura coupling or cycloadditions - before undertaking the oximation step - provided accesses to further α-amino esters. Moreover, other pathways to α-hydroxyimino esters were explored including an attempt to improve the cycloadditions between ethyl β-bromo-α-hydroxyiminocarboxylate and various alkylfuranes.
- Coutant, Eloi P.,Hervin, Vincent,Gagnot, Glwadys,Ford, Candice,Baatallah, Racha,Janin, Yves L.
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supporting information
p. 2853 - 2860
(2018/11/26)
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- Functionalization of dipyrromethanes via hetero-Diels-Alder reaction with azo- and nitrosoalkenes
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5,5′-Diethyl- and 5-phenyldipyrromethanes participate in cycloadditions with azo- and nitrosoalkenes giving dipyrromethanes with side chains containing open chain oximes and hydrazones. By controlling reaction stoichiometry it is possible to get mono or 1
- Pereira, Nelson A.M.,Lemos, Américo,Serra, Arménio C.,Pinho E Melo, Teresa M.V.D.
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p. 1553 - 1557
(2013/03/14)
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- PHARMACEUTICAL COMPOSITION CONTAINING FUSED HETERO-RING DERIVATIVE
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The present invention provides a compound which indicates a histamine H4 receptor modulating activity.A compound represented by a formula (I): wherein A ring is a ring represented by the following formula: wherein R1 is substituted or unsubstituted alkyl, etc., W is -O-, etc., n is an integer of 0 to 6; X is N(R7)- or -O-; R7 is hydrogen, substituted or unsubstituted alkyl, etc.; Y is-C(R8)= or -N=; R8 is hydrogen, substituted or unsubstituted alkyl, etc.; Z is =O, =S, etc.; B ring is a ring represented by the following formula wherein R10 is each independently substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted alkyloxy, substituted or unsubstituted amino; R11, R12a and R12b are each independently hydrogen or substituted or unsubstituted alkyl, etc.; p is an integer of 0 to 4, or its pharmaceutically acceptable salt, or a solvate thereof.The present invention provides a compound which indicates a histamine H4 receptor modulating activity. A compound represented by a formula (I): wherein A ring is a ring represented by the following formula: wherein R 1 is substituted or unsubstituted alkyl, etc., W is -O-, etc., n is an integer of 0 to 6; X is N(R 7 )- or -O-; R 7 is hydrogen, substituted or unsubstituted alkyl, etc.; Y is-C(R 8 )= or -N=; R 8 is hydrogen, substituted or unsubstituted alkyl, etc.; Z is =O, =S, etc.; B ring is a ring represented by the following formula wherein R 10 is each independently substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted alkyloxy, substituted or unsubstituted amino; R 11 , R 12a and R 12b are each independently hydrogen or substituted or unsubstituted alkyl, etc.; p is an integer of 0 to 4, or its pharmaceutically acceptable salt, or a solvate thereof.
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Page/Page column 85
(2012/06/18)
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- Unprecedented formation of Δ2-isoxazoline and/or 1-nitroso-pyrazoline from α-bromoketone oximes and diazo compounds
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Reaction of α-bromoketone oximes with diazo compounds in the presence of a metal catalyst and base led to the unprecedented formation of two types of rings: Δ2-isoxazolines and 1-nitrosopyrazolines.
- Guo, Jianhua,Gaudette, John,Cheng, Jie-Fei
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supporting information; experimental part
p. 933 - 935
(2009/05/11)
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- Synthesis and activity of tryptophan sulfonamide derivatives as novel non-hydroxamate TNF-α converting enzyme (TACE) inhibitors
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A novel series of non-hydroxamate tryptophan sulfonamide derivatives containing a butynyloxy P1′ moiety was identified as inhibitors of TNF-α converting enzyme (TACE). The structure-activity relationship of the series was examined via substitution on the
- Park, Kaapjoo,Gopalsamy, Ariamala,Aplasca, Alexis,Ellingboe, John W.,Xu, Weixin,Zhang, Yuhua,Levin, Jeremy I.
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experimental part
p. 3857 - 3865
(2009/09/30)
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- Derivatives of psammaplin A, a method for their synthesis and their use for the prevention or treatment of cancer
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Derivatives of psammaplin A of formula (I), a method for their synthesis and their use for the preparation of a medicament for preventing and /or treating a tumor or a cancer.
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Page/Page column 11
(2008/12/08)
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- Kinase inhibitors
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Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.
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Page/Page column 66
(2010/01/31)
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- Chemical compounds
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Compounds of the general structural formula (I) and use of the compounds and salts and solvates thereof, as therapeutic agents.
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- Addition and Cycloaddition Reactions of the Electrophilic Vinyl Nitroso Compounds 3-Nitrosobut-3-en-2-one, 2-Nitrosopropenal, and Ethyl 2-Nitrosopropenoate
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1-Chlorobutane-2,3-dione 2-oxime (2a) reacts with sodium carbonate and, in the presence of olefins, gives the oxazines (4) stereoselectively and in good yield. 3-Nitrosobut-3-en-2-one (1a) is postulated to be the intermediate in these reactions.Similar additions occur with 3-chloro-2-hydroxyiminopropanal (2b) and with ethyl bromopyruvate 2-oxime (3), although the oxazines are generally formed in lower yield.Competition experiments using pairs of olefins indicate that the intermediate (1a) adds preferentially to electron-rich olefins.The vinyl nitroso intermediates (1) act as electrophiles towards indole; the products are the corresponding 3-alkylindoles (11).Analogous reactions are observed with pyrrole, 1-methylpyrrole, 1,3-dimethoxybenzene, and NN-dimethylaniline; with 3-methylindole, addition takes place at the 3-position to give the cycloadducts (12). 3-Nitrosopent-3-en-2-one (19) has been generated from 4-chloropentane-2,3-dione 3-oxime.This vinyl nitroso intermediate also undergoes cycloaddition to olefins, in competition with a hydrogen shift from the terminal methyl group which leads to isomerisation to pent-2-ene-2,3-dione 3-oxime (20).
- Gilchrist, Thomas L.,Roberts, Tony G.
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p. 1283 - 1292
(2007/10/02)
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