- Design, synthesis and biological evaluation of 6-deoxy O-spiroketal C-arylglucosides as novel renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes
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In this work, aiming at finding a novel, potent, and selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor with good pharmacokinetic profiles for the treatment of diabetes, we focus on modifying the sugar moiety of SGLT2 inhibitors, which dominates the binding with glucose binding site of hSGLT, via removing the C-6 hydroxy group to adjust the physicochemical properties and target-recognition manners of SGLT2 inhibitors. In addition, tofogliflozin containing a special O-spiroketal C-arylglucoside scaffold, displayed good efficacy and bioavailability both in animals and in humans. Therefore, a series of 6-deoxy O-spiroketal C-arylglucosides as novel SGLT2 inhibitors were designed, synthesized, and evaluated in this work. The structure-activity relationship (SAR) research on this novel series and a comprehensive in vitro and in vivo biological evaluation afforded compound 39 with high in vitro hSGLT2 inhibitory activity (IC50 = 4.5 nM), good pharmacokinetic profiles, and more remarkable efficacy in C57BL/6J mice and Sprague-Dawley rats than marketed drug tofogliflozin.
- Wang, Yibing,Lou, Yang,Wang, Jiang,Li, Dan,Chen, Hui,Zheng, Tiannan,Xia, Chunmei,Song, Xiaohan,Dong, Tiancheng,Li, Jingya,Li, Jia,Liu, Hong
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p. 398 - 416
(2019/07/19)
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- C,O-SPIRO ARYL GLYCOSIDE COMPOUNDS, PREPARATION THEREFOR AND USE THEREOF
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The present invention provides C, O-spiro aryl glycoside compounds, preparation therefor and use thereof. Specifically provided are the compounds represented by the formula (I), wherein the definitions of each group are described in the specification. The
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- Iodine monochloride (ICl) as a highly efficient, green oxidant for the oxidation of alcohols to corresponding carbonyl compounds
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Iodine monochloride (ICl) was discovered to be a highly efficient, green oxidant, which can oxidize aldose hemiacetals, diarylmethanols, arylalkylmethanols, anddialkylmethanols to the corresponding aldose lactones, diarylmethanones, arylalkylmethanones, and dialkylmethanones, respectively, in high yields. ICl as a green, metal-free oxidant is characterized by mild reaction condition, short reaction time, good yield, and broad scope.
- Wei, Peng,Zhang, Datong,Gao, Zhigang,Cai, Wenqing,Xu, Weiren,Tang, Lida,Zhao, Guilong
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p. 1457 - 1470
(2015/05/20)
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- PHENYL C-GLUCOSIDE DERIVATIVE CONTAINING DEOXYGLUCOSE STRUCTURE, PREPARATION METHOD AND USE THEREOF
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The present invention provides a phenyl C-glucoside derivative containing a deoxyglucose structure as represented by formula I, preparation method thereof, a pharmaceutical composition comprising the same, and uses thereof in the preparation of medicament
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Paragraph 0249; 0250; 0251; 0252
(2015/11/09)
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- Mannose-binding geometry of pradimicin A
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Pradimicins (PRMs) and benanomicins are the only family of non-peptidic natural products with lectin-like properties, that is, they recognize D-mannopyranoside (Man) in the presence of Ca2+ ions. Coupled with their unique Man binding ability, t
- Nakagawa, Yu,Doi, Takashi,Taketani, Takara,Takegoshi,Igarashi, Yasuhiro,Ito, Yukishige
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supporting information
p. 10516 - 10525
(2013/08/23)
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- A facile synthesis of 6-deoxydapagliflozin
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A facile synthesis of a potent SGLT2 inhibitor, 6-deoxydapagliflozin, from methyl 2,3,4-tri-O-benzyl-6-deoxy-6-iodo-α-d-glucopyranoside in six steps with an overall yield of 50 % is described. The key steps were the reductive deiodination of the starting
- Shi, Yongheng,Xu, Huaqiang,Liu, Bingni,Kong, Weiling,Wei, Qunchao,Xu, Weiren,Tang, Lida,Zhao, Guilong
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p. 1903 - 1910
(2014/01/06)
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- β-Rhamnosides from 6-thio mannosides
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Upon condensation of 6-thio-6-deoxy-mannosyl donors 1,2-cis products are obtained with a high degree of stereoselectivity. Subsequent reductive removal of the 6-thio functionality gives 1,2-cis rhamnosides. The 1,2-cis-selectivity can be rationalized with
- Christina, Alphert E.,Es, Daan Van Der,Dinkelaar, Jasper,Overkleeft, Hermen S.,Marel, Gijsbert A. Van Der,Codee, Jeroen D. C.
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supporting information; experimental part
p. 2686 - 2688
(2012/04/10)
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- Zinc-mediated fragmentation of methyl 6-deoxy-6-iodo-hexopyranosides
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An improved procedure was developed for the zinc-mediated fragmentation of protected and unprotected methyl 6-deoxy-6-iodo-hexopyranosides. The method employs sonication of the iodoglycoside with zinc dust in a THF/H2O mixture.
- Skaanderup, Philip R.,Hyldtoft, Lene,Madsen, Robert
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p. 467 - 472
(2007/10/03)
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- The use of a new magnesium-derived hydride reagent for carbohydrate derivatives
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The magnesium hydride based reagent in THF solution is an excellent tool for the stereoselective reduction of different uloside derivatives. Sugar azides, sulfonyl esters give aminosugars and methylose derivatives without affecting other functionalities. Halogenated sugars or methylene derivatives are stable under these conditions. The reagent can be applied in the presence of a wide variety of blocking groups (acetals, benzyl and allyl ethers, imides, C=C bonds) generally used in the carbohydrate chemistry.
- Szabovik,Medgyes,Antal,Varga,Knott,Liptak
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p. 1003 - 1009
(2007/10/03)
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- Synthesis of trehazolin analogues containing modified sugar moieties
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In order to elucidate the biological roles of the sugar moiety of the trehalase inhibitor trehazolin 1, the sugar portion was first replaced with hydrophobic aromatic functions, providing the N-phenyl 3 and N-benzyl derivatives 4 of trehazolin 1.Then the six analogues with the sugar moiety being replaced with D-mannopyranose 5, 3-deoxy-ribo-hexopyranose 6, D-galactopyranose 7, 6-deoxy-D-glucopyranose 8, 5a-carba-α-D-glucopyranose 9 and 5a-carba-α-D-xylo-hex-5(5a)-enopyranose residues 10 were synthesized.In the hope of improving the fungicidal activity of trehazolin 1. we prepared two disaccharide analogues, 11 and 12, containing maltose and cellobiose residues.A remarkable decrease in potency was observed in the analogues 5-8 and 10, but not for 5a'-carbatrehazolin 9, suggesting an essential role for the D-gluco configuration of the hexopyranose portion.The β-D-glucosyl analogue 12 showed an increase in antifungal activity against Rhizoctonia solani, as compared with that of trehazolin 1.The nalogues 3 and 4 were not trehalase inhibitors, but rather were moderate α-glucosidase inhibitors.
- Uchida, Chikara,Kitahashi, Hideo,Watanabe, Shinsuke,Ogawa, Seiichiro
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p. 1707 - 1718
(2007/10/02)
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- Diastereoselectivity in the intramolecular nitrone, oxime, and nitrile oxide cycloaddition reactions. Synthesis of amino inositol derivatives as α-glucosidase inhibitors
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The diastereoselectivity in the intramolecular 1,3-dipolar cycloaddition reactions of 4 and 5 (R=Bn, 4-MeOBn) was examined.
- Peet, Norton P.,Huber, Edward W.,Farr, Robert A.
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p. 7537 - 7550
(2007/10/02)
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- SYNTHESIS OF CYTIDINE DIPHOSPHATE-D-QUINOVOSE
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The title molecule, cytidine-D-quinovose (CDP-6-deoxy-D-glucose) 1, was synthesized by two different methods from the key intermediate quinovose-1-phosphate 7 which was prepared from glucose.
- Liu, Li-da,Liu, Hung-wen
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- Partially Benzylated Derivatives of 6-Deoxy-D-glucose
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Several partially benzylated derivatives of 6-deoxy-D-glucose (D-quinovose) were synthesized from appropriate di-O-benzyl-D-glucosides whose primary hydroxyl group is unprotected, via unimolar tosylation and subsequent reduction with LiAlH4.
- Koto, Shinkiti,Morishima, Naohiko,Mori, Yoko,Tanaka, Hitoshi,Hayashi, Seiichi,et al.
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p. 2301 - 2303
(2007/10/02)
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- SYNTHESIS OF (1->1)-BONDED RHAMNOPYRANOSYL-RHAMNOPYRANOSIDES CONTAINING L,L AND L,D BUILDING-STONES. HIGH-FIELD 1H- AND 13C-NMR SPECTROSCOPIC STUDIES ON THE CONFORMATION OF THE INTERGLYCOSIDIC BONDS
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Rhamnosylation of 2,3,4-tri-O-acetyl-L- (1) and 2,3,4-tri-O-benzyl-D-rhamnopyranose (9) with α-acetobromo-L-rhamnose resulted in fully protected α-L, α-L-, α-L, β-L-, α-D,α-L-, and β-D,α-L-rhamnopyranosyl-rhamnopyranosides.The signal of the anomeric carbo
- Liptak, A.,Goendoer, A.
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p. 309 - 322
(2007/10/02)
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- A Study of the Rapid Anomerization of Poly-O-benzyl-β-D-glucopyranosides with Titanium Tetrachloride
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Titanium tetrachloride rapidly anomerizes methyl 2,3,4,6-tetra-O-benzyl-β-D-glucopyranoside in dichloromethane at 25 deg C.Evidence for the proposal that the benzyloxymethyl group on C-5 and the ring oxygen of the glucoside cooperate to prompt the reaction is described.The reagent anomerizes the interglycosidic linkage of several disaccharide derivatives.
- Koto, Shinkiti,Morishima, Naohiko,Kawahara, Reiko,Ishikawa, Katsuhiko,Zen, Shonosuke
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p. 1092 - 1096
(2007/10/02)
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