Novel thiophene C-aryl glucoside SGLT2 inhibitors were designed and synthesized. Two different types of thiophene derivatives were readily prepared. Among the compounds tested, ethylphenyl at the distal ring 71p showed the best in vitro inhibitory activity in this series to date (IC(50)=4.47 nM) against SGLT2.
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http://dx.doi.org/10.1016/j.bmc.2011.08.014 | DOI Listing |
J Pharm Biomed Anal
May 2022
Chemical Process Development, Global Product Development and Supply, Bristol Myers Squibb Company, New Brunswick, New Jersey, USA.
Solution stability of analytes plays an important part in qualitative analysis, especially in conducting accurate, quantitative analyses. Sample diluents and glass vials as sample containers for HPLC analyses can play a critical role and should be evaluated during chromatographic method development. We have encountered several instances during pharmaceutical development where the glass vial/diluent combination has negatively impacted method performance.
View Article and Find Full Text PDFBioorg Med Chem Lett
January 2022
R&D Division, GC Pharma, Gyeonggi-do, Republic of Korea. Electronic address:
Sodium-dependent glucose co-transporter 2 (SGLT2) has emerged as a promising drug target for the treatment of type 2 diabetes, and recently, several SGLT2 inhibitors have been approved for clinical use. A series of molecules with a C-aryl glucoside scaffold was designed and synthesized for biological evaluation. Among the molecules tested, a dihydrobenzofuran-containing analog, 14g (GCC5694A), exhibited excellentin vitro activity against SGLT2 (IC = 0.
View Article and Find Full Text PDFChem Rec
November 2021
Department of Chemistry, Indian Institute of Technology Madras, Chennai, 600036, India.
Natural products, remains the most important source for the discovery of new drugs for the treatment of human diseases. This has inspired the synthetic community to design and develop mimics of natural products either to answer important questions in biology or to explore their therapeutic potentials. Glycosides present themselves abundantly in nature, right from the cell surface receptors to natural products of any origin.
View Article and Find Full Text PDFBioorg Med Chem Lett
September 2020
Discovery Sciences and Metabolic Research, Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, United States.
(2S,3R,4R,5S,6R)-2-Aryl-5,5-difluoro-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4-diols and (2S,3R,4R,5S,6R)-2-aryl-5-fluoro-5-methyl-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4-diols were discovered as dual inhibitors of sodium glucose co-transporter proteins (e.g. SGLT1 and SGLT2) through rational drug design, efficient synthesis, and in vitro and in vivo evaluation.
View Article and Find Full Text PDFXenobiotica
May 2020
Molecular Medicine Research Institute, Sunnyvale, CA, USA.
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