Synthesis and Structure-Activity Relationship of C-Phenyl D-Glucitol (TP0454614) Derivatives as Selective Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitors.

In this study we found a new method of synthesizing key intermediates 12 by a one-pot three-component condensation reaction and discovered C-phenyl D-glucitol 41j (TP0454614), which has >40-fold SGLT1 selectivity in vitro (IC50 26 nM for hSGLT1 and 1101 nM for hSGLT2). The results of our study have provided new insights into the structure-activity relationships (SARs) of the SGLT1 selectivity of C-glucitol derivatives.
PMID: 32611999 [PubMed - in process]

Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Kuroda S, Kobashi Y, Kawamura M, Kawabe K, Shiozawa F, Hamada M, Shimizu Y, Okumura-Kitajima L, Koretsune H, Kimura K, Yamamoto K, Kakinuma H Tags: Chem Pharm Bull (Tokyo) Source Type: research