title: Systematic syntheses of influenza neuraminidase inhibitors: a series of carbosilane dendrimers uniformly functionalized with thioglycoside-type sialic acid moieties.
abstract: In order to develop novel influenza sialidase inhibitors, we constructed a library of glycoclusters composed of twelve types of sialylated dendrimers with thioglycosidic linkage that are resistant to hydrolysis by the sialidases. These sialodendrimers were synthesized by condensation reaction between a thiosialoside modified on the aglycon terminal end by a thioacetyl group and twelve types of carbosilane dendrimers having brominated terminal ends under deacetylation conditions, and temporal re-protection was performed for purification. Removal of all protection of the glycodendrimers was accomplished by transesterification and subsequent saponification to provide corresponding water-soluble glycodendrimers in good yields. For investigation of the structure-activity relationship, dendrimer scaffolds having differences in number of the sugar moieties, such as 3-, 4-, 6- and 12-functionalized dendrimers, and in linkage patterns, such as normal aliphatic linkage, ether- and amide-linkages. Biological evaluations of these glycodendrimers showed that all of the ether- and amide-elongated compounds had inhibitory potencies for the influenza sialidases in the mM range, while compounds having normal aliphatic linkage did not have any activities except for a 12-functionalized compound.
authors: Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan.
authors: Jun-ichi
authors: J
authors: Sakamoto
authors: Tetsuo
authors: T
authors: Koyama
authors: Daisei
authors: D
authors: Miyamoto
authors: Sangchai
authors: S
authors: Yingsakmongkon
authors: Kazuya I P J
authors: KI
authors: Hidari
authors: Wipawee
authors: W
authors: Jampangern
authors: Takashi
authors: T
authors: Suzuki
authors: Yasuo
authors: Y
authors: Suzuki
authors: Yasuaki
authors: Y
authors: Esumi
authors: Takemichi
authors: T
authors: Nakamura
authors: Ken
authors: K
authors: Hatano
authors: Daiyo
authors: D
authors: Terunuma
authors: Koji
authors: K
authors: Matsuoka
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology*; D007251:Influenza, Human / Q000188:drug therapy; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012821:Silanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013865:Thioglycosides / Q000737:chemistry; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D050091:Dendrimers; D012821:Silanes; D013865:Thioglycosides; D014764:Viral Proteins; C504072:carbosilane; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid