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21 results on '"Toyofuku, Masashi"'

5. T-448, a specific inhibitor of LSD1 enzyme activity, improves learning function without causing thrombocytopenia in mice

Author

Matsuda, Satoru, primary, Baba, Rina, additional, Oki, Hideyuki, additional, Morimoto, Shinji, additional, Toyofuku, Masashi, additional, Igaki, Shigeru, additional, Kamada, Yusuke, additional, Iwasaki, Shinji, additional, Matsumiya, Kota, additional, Hibino, Ryosuke, additional, Kamada, Hiroko, additional, Hirakawa, Takeshi, additional, Iwatani, Misa, additional, Tsuchida, Ken, additional, Hara, Ryujiro, additional, Ito, Mitsuhiro, additional, and Kimura, Haruhide, additional

Published
2018
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6. Platinum-catalyzed intramolecular vinylchalcogenation of alkynes with [beta]-phenylchalcogeno conjugated amides

Author

Toyofuku, Masashi, Fujiwara, Shin-Ichi, Shin-ike, Tsutomu, Kuniyasu, Hitoshi, and Kambe, Nobuaki

Subjects
Platinum -- Chemical properties, Platinum -- Structure, Chemistry
Abstract

Pt[(P[Ph.sub.3]).sub.4] has catalyzed intramolecular vinylthiolation and -selenation of internal alkynes with vinyl chalcogenides having a carbamoyl group on the cis-[beta]-position of the vinyl moiety, thus giving rise to the highly conjugated [delta]-lactam frameworks. The alkyne insertion processes has shown that the formation of seven-membered platinacycle is kinetically favored and the introduction of electron withdrawing groups to [beta]-position on vinyl moiety is vital for developing new type of catalytic reaction by using vinyl heteroatom compounds.

Published
2008

7. Palladium-catalyzed intramolecular selenocarbamoylation of alkynes with carbamoselenoates: Formation of alpha-alkylidene-beta-lactam framework

Author

Toyofuku, Masashi, Fujiwara, Shin-ich, Shin-ike, Tsutomu, Kuniyasu, Hitoshi, and Kambe, Nobuaki

Subjects
Palladium -- Chemical properties, Chemistry
Abstract

Pd catalyzes intramolecular selenocarbamoylation of alkynes is discovered to give alpha-alkylidenelactams. The possibility of selenocarbamoylation is examined by reacting a carbamoselenoate, PhSe-C(O)-NMe2, with an alkyne.

Published
2005

8. T-448, a specific inhibitor of LSD1 enzyme activity, improves learning function without causing thrombocytopenia in mice

Author

Matsuda, Satoru, Baba, Rina, Oki, Hideyuki, Morimoto, Shinji, Toyofuku, Masashi, Igaki, Shigeru, Kamada, Yusuke, Iwasaki, Shinji, Matsumiya, Kota, Hibino, Ryosuke, Kamada, Hiroko, Hirakawa, Takeshi, Iwatani, Misa, Tsuchida, Ken, Hara, Ryujiro, Ito, Mitsuhiro, and Kimura, Haruhide

Abstract

Dysregulation of histone H3 lysine 4 (H3K4) methylation has been implicated in the pathogenesis of several neurodevelopmental disorders. Targeting lysine-specific demethylase 1 (LSD1), an H3K4 demethylase, is therefore a promising approach to treat these disorders. However, LSD1 forms complexes with cofactors including growth factor independent 1B (GFI1B), a critical regulator of hematopoietic differentiation. Known tranylcypromine-based irreversible LSD1 inhibitors bind to coenzyme flavin adenine dinucleotide (FAD) and disrupt the LSD1-GFI1B complex, which is associated with hematotoxicity such as thrombocytopenia, representing a major hurdle in the development of LSD1 inhibitors as therapeutic agents. To discover LSD1 inhibitors with potent epigenetic modulation and lower risk of hematotoxicity, we screened small molecules that enhance H3K4 methylation by the inhibition of LSD1 enzyme activity in primary cultured rat neurons but have little impact on LSD1-GFI1B complex in human TF-1a erythroblasts. Here we report the discovery of a specific inhibitor of LSD1 enzyme activity, T-448 (3-((1S,2R)-2-(cyclobutylamino)cyclopropyl)-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamide fumarate). T-448 has minimal impact on the LSD1-GFI1B complex and a superior hematological safety profile in mice via the generation of a compact formyl-FAD adduct. T-448 increased brain H3K4 methylation and partially restored learning function in mice with NMDA receptor hypofunction. T-448-type LSD1 inhibitors with improved safety profiles may provide unique therapeutic approaches for central nervous system disorders associated with epigenetic dysregulation.

Published
2019
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21. Palladium-Catalyzed Intramolecular Selenocarbamoylation of Alkynes with Carbamoselenoates: formation of α-Alkylidene-β-lactam Framework.

Author

Toyofuku, Masashi, Fujiwara, Shin-ich, Shin-ike, Tsutomu, Kuniyasu, Hitoshi, and Kambe, Nobuaki

Subjects
*PALLADIUM catalysts, *CARBON, *ESTERS, *ALKENES, *CHALCOGENS, *PLATINUM catalysts
Abstract

This article focuses on palladium-catalyzed intramolecular selenocarbamoylation of alkynes with carbamoselenoates. Transition-metal-catalyzed addition of organochalcogen compounds to alkynes with cleavage of bonds is a promising synthetic route to functionalized alkenes. The more attractive and challenging theme of interest would be the insertion of C-C unsaturated units across chalcogen-carbon bonds that can construct new chalcogen-carbon and carbon-carbon bonds in one step, this transformation remains much less explored. The authors have shown that thiol esters and selenol esters undergo decarbonylative addition to alkynes in the presence of platinum catalysts. The authors discloses that palladium catalyzes intramolecular selenocarbamoylation of alkynes to give α-alkylidenelactams.

Published
2005
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