1154956-96-3Relevant academic research and scientific papers
Antidiabetic compound and preparation method and application thereof
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Paragraph 0058; 0059; 0060, (2017/09/19)
The invention discloses an antidiabetic compound and a preparation method and application thereof, and belongs to the technical field of medicine. The chemical structure of the compound is shown as a formula (I) (please see the formula in the description), wherein R is selected from i-Pr, Cl and COCH2Cl. According to the antidiabetic compound and the preparation method and application thereof, 2-chloro-5-bromobenzoic acid and D-gluconolactone are taken as starting raw materials, and three Dapagliflozin derivatives are finally obtained through reacting; the optimal reaction condition of different positioning groups is determined according to the reaction conditions of a Friede-Crafts alkylation reaction of the different positioning groups; in addition, a novel stereoisomerism splitting method is applied, therefore, the reaction conditions are optimized, the reaction cost is greatly lowered, the yield is increased, the used raw materials are cheap and easy to obtain, and the wide applicability is achieved.
Synthesis and biological evaluation of novel C-aryl D-glucofuranosides as sodium-dependent glucose co-transporter 2 inhibitors
Lin, Tzung-Sheng,Liw, Ya-Wen,Song, Jen-Shin,Hsieh, Tsung-Chih,Yeh, Hsien-Wei,Hsu, Lih-Ching,Lin, Chun-Jung,Wu, Szu-Huei,Liang, Pi-Hui
, p. 6282 - 6291 (2013/10/22)
Novel C-aryl-d-glucofuranosides were synthesized and evaluated for their capacity to inhibit human sodium-dependent glucose co-transporter 2 (hSGLT2) and hSGLT1. Compound 21q demonstrated the best in vitro inhibitory activity against SGLT2 in this series (EC50 = 0.62 μM).
(1 S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio- d -glucitol (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes treatment
Kakinuma, Hiroyuki,Oi, Takahiro,Hashimoto-Tsuchiya, Yuko,Arai, Masayuki,Kawakita, Yasunori,Fukasawa, Yoshiki,Iida, Izumi,Hagima, Naoko,Takeuchi, Hiroyuki,Chino, Yukihiro,Asami, Jun,Okumura-Kitajima, Lisa,Io, Fusayo,Yamamoto, Daisuke,Miyata, Noriyuki,Takahashi, Teisuke,Uchida, Saeko,Yamamoto, Koji
experimental part, p. 3247 - 3261 (2010/10/02)
Derivatives of a novel scaffold, C-phenyl 1-thio-d-glucitol, were prepared and evaluated for sodium-dependent glucose cotransporter (SGLT) 2 and SGLT1 inhibition activities. Optimization of substituents on the aromatic rings afforded five compounds with potent and selective SGLT2 inhibition activities. The compounds were evaluated for in vitro human metabolic stability, human serum protein binding (SPB), and Caco-2 permeability. Of them, (1S)-1,5-anhydro-1-[5- (4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-d-glucitol (3p) exhibited potent SGLT2 inhibition activity (IC50 = 2.26 nM), with 1650-fold selectivity over SGLT1. Compound 3p showed good metabolic stability toward cryo-preserved human hepatic clearance, lower SPB, and moderate Caco-2 permeability. Since 3p should have acceptable human pharmacokinetics (PK) properties, it could be a clinical candidate for treating type 2 diabetes. We observed that compound 3p exhibits a blood glucose lowering effect, excellent urinary glucose excretion properties, and promising PK profiles in animals. Phase II clinical trials of 3p (TS-071) are currently ongoing.
