Compounds Currently in Phase II−III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas Yu Zhou,† Jiang Wang,† Zhanni Gu,† Shuni Wang,† Wei Zhu,† Jose ́ Luis Aceña,*,‡,§ Vadim A. Soloshonok,*,‡,∥ Kunisuke Izawa,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastiań, Spain Department of Organic Chemistry, Autońoma University of Madrid, Cantoblanco, 28049 Madrid, Spain IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, 48013 Bilbao, Spain Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, Japan 533-0024

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

There are two classes of glucose transporters involved in glucose homeostasis in the body, the facilitated transporters or uniporters (GLUTs) and the active transporters or symporters (SGLTs). The ...

Biology of Human Sodium Glucose Transporters

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Albumin Fusion Proteins

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)60749-0.pdf

Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin:a randomised, double-blind, placebo-controlled trial

Natural products: an evolving role in future drug discovery.

The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.

Discovery of Dapagliflozin: A Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

An SGLT2 inhibiting compound is provided having the formula[Chemical structure] A method is also provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.

C-aryl glucoside SGLT2 inhibitors and method

SGLT2 inhibiting compounds are provided having formula (I) where R?1, R2, and R2a? are independently hydrogen, OH, OR5, lower alkyl, CF?3?, OCHF2, OCF3, SR?5i? or halogen, or two of R?1, R2 and R2a? together with the carbons to which they are attached can form an annelated five, six or seven membered carbocycle or heterocycle; R?3 and R4? are independently hydrogen, OH, OR5a, OAryl, OCH?2?Aryl, lower alkyl, cycloalkyl, CF3, -OCHF2, -OCF3, halogen, -CN, -CO2R?5b, -CO?2H, -COR6b, -CH(OH)R6c, -CH(OR?5h)R6d, -CONR6R6a?, -NHCOR5c, -NHSO?2R?5d, -NHSO?2?Aryl, Aryl, -SR?5e, -SOR5f, SO?2R5g, SO2Aryl, or a five, six or seven membered heterocycle, or R?3 and R4? together with the carbons to which they are attached form an annelated five, six or seven membered carbocycle or heterocycle; R?5, R5a, R5b, R5c, R5d, R5e, R5f, R5g, R5h, and R5I? are independently lower alkyl; R?6, R6a, R6b, R6c and R6d? are independently hydrogen, alkyl, aryl, alkylaryl or cycloalkyl, or R?6 and R6a? together with the nitrogen to which they are attached form an annelated five, six or seven membered heterocycle; A is O, S, NH, or (CH?2?)n where n is 0 - 3. A method is also provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.

C-aryl glucoside SGLT2 inhibitors

Formula (I) wherein Y is formula (a) or heteroaryl; A is -O(CH2)m, S, -NH(CH2)m, or (CH2)n where n is 0-3 and m is 0-2; and R1 to R6 are as defined herein. A method is also provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with one, two or more other antidiabetic agents, and/or one, two or more hypolipidemic agents.

Gang Wu

Papers

Discovery of Dapagliflozin: A Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

C-aryl glucoside SGLT2 inhibitors and method

C-aryl glucoside SGLT2 inhibitors

O-aryl glucoside SGLT2 inhibitors and method

Aglycone exploration of C-arylglucoside inhibitors of renal sodium-dependent glucose transporter SGLT2.