- Rhodium-Catalyzed C4-Selective C-H Alkenylation of 2-Pyridones by Traceless Directing Group Strategy
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A rhodium-catalyzed C4-selective C-H alkenylation of 3-carboxy-2-pyridones with styrenes has been developed. The carboxylic group at the C3 position works as the traceless directing group, and the corresponding C4-alkenylated 2-pyridones are obtained exclusively with concomitant decarboxylation. Unlike the reported procedures, the exclusive C4 selectivity is uniformly observed even in the presence of potentially more reactive C-H bonds at the C5 and C6 positions. By using this strategy, the multiply substituted 2-pyridone can be prepared via sequential C-H functionalization reactions.
- Hazra, Sunit,Hirano, Koji,Miura, Masahiro
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supporting information
p. 1388 - 1393
(2021/03/03)
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.
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Page/Page column 347; 348
(2020/10/20)
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
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Page/Page column 340-342
(2019/10/15)
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- PYRIDINONES
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The present invention encompasses compounds of general formula (I) wherein the groups R1 to R3 and X1 through X6 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
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Page/Page column 44; 45; 46; 47; 48
(2015/02/25)
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- Indazole-and indole-5-carboxamides: Selective and reversible monoamine oxidase B inhibitors with subnanomolar potency
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Indazole-and indole-carboxamides were discovered as highly potent, selective, competitive, and reversible inhibitors of monoamine oxidase B (MAO-B). The compounds are easily accessible by standard synthetic procedures with high overall yields. The most potent derivatives were N-(3,4- dichlorophenyl)-1-methyl-1H-indazole-5-carboxamide (38a, PSB-1491, IC 50 human MAO-B 0.386 nM, >25000-fold selective versus MAO-A) and N-(3,4-dichlorophenyl)-1H-indole-5-carboxamide (53, PSB-1410, IC50 human MAO-B 0.227 nM, >5700-fold selective versus MAO-A). Replacement of the carboxamide linker with a methanimine spacer leading to (E)-N-(3,4- dichlorophenyl)-1-(1H-indazol-5-yl)methanimine (58) represents a further novel class of highly potent and selective MAO-B inhibitors (IC50 human MAO-B 0.612 nM, >16000-fold selective versus MAO-A). In N-(3,4- difluorophenyl-1H-indazole-5-carboxamide (30, PSB-1434, IC50 human MAO-B 1.59 nM, selectivity versus MAO-A >6000-fold), high potency and selectivity are optimally combined with superior physicochemical properties. Computational docking studies provided insights into the inhibitors' interaction with the enzyme binding site and a rationale for their high potency despite their small molecular size.
- Tzvetkov, Nikolay T.,Hinz, Sonja,Küppers, Petra,Gastreich, Marcus,Müller, Christa E.
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supporting information
p. 6679 - 6703
(2014/11/07)
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- NEW 2-AMIDOTHIADIAZOLE DERIVATIVES
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New 2-amidothiadiazole derivatives having the chemical structure of formula (I) or pharmaceutically acceptable salts or N-oxides thereof as agonists of S1P1 receptors.
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Page/Page column 66
(2010/04/30)
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- MGluR5 modulators I
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The present invention is directed to novel compounds, to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds.
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Page/Page column 29
(2008/06/13)
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- Substituent Effects in Non-Aromatic Nitrogen Heterocycles: Alkaline Hydrolysis of Methyl N-Methyl(oxo)dihydropyridinecarboxylates and Diaza Analogues
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Ester hydrolysis studies on some isomeric methoxycarbonyl derivatives of N-methylpyridin-2- and 4-ones show that reaction rates are affected by the relative positions of CO2Me, =O and NMe functions in ways which could not be predicted.However, from limited results for analogous pyrimidine derivatives, it seems that reactivity in these polyfunctional compounds can be predicted from the pyridine data by assuming additivity of effects.
- Deady, Leslie W.
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p. 637 - 641
(2007/10/02)
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- The Role of 2-α-Hydroxy- and 2-α-Oxo-2,3-cycloalkenopyridinium Intermediates During Decker Oxidation of Hydrogenated Cycloalkapyridinium Salts
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In alkaline solution pyridinium salts 3 readily undergo hydrolysis to betains 4 which are oxidized by hexacyanoferrate(III) to a mixture of isomeric carboxylic acids 5 and 6 in excellent yields.Decker oxidation of compounds 2 results in the pyridones 11 as main products.Formation of 5 and 6 via intermediates 3 and 4 is realized only in case of the lower homologues 2 (n = 2,3) and has no quantitative significance.Predominantly oxidative cleavage of the carbocycle in 2 occurs directly with simultaneous formation of the 2-pyridone structure and elimination of 2-α-C asan aldehyde function.Resulting stable reaction products are α-hydroxycarboxylic acids 12 and acids 5 with a shortened aliphatic side chain.It is demonstrated that 2 and 3 are not necessarily formed as intermediates during the conversion of 1 into 5 by means of Decker oxidation.
- Weber, Horst,Lippe, Gotelind von der
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p. 4086 - 4098
(2007/10/02)
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- Treatment of psoriasis with nicotinamide analogues
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A treatment to alleviate the symptoms of psoriasis consisting of topical application of a cream, lotion, ointment or gel containing as the principal active ingredient one or more nicotinamide analogues is disclosed. The therapeutic composition may include a single member of the above active ingredients present in a total amount of from 0.01 to 5 percent by weight of the total composition or a plurality thereof present in a preferred concentration range of from 0.02 to 2 percent by weight of the total composition. Topical application of the therapeutic composition in a cream, ointment, lotion, water or gel has been found to achieve from substantial to complete remissions of psoriasis in humans.
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