19094-56-5Relevant articles and documents
Synthesis of Benzyl C-Analogues of Dapagliflozin as Potential SGLT2 Inhibitors
Aidhen, Indrapal Singh,Banerjee, Sanjay K.,Kumar, Roshan,Mukkamala, Ramesh
, (2020)
Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes based on blocking of renal reabsorption of glucose. Dapagliflozin, a C-aryl glucoside, has emerged as a successful drug in the market based on this concept. We have synthesized hitherto unreported C-benzyl glucoside analogues of Dapagliflozin carrying the same aglycon present in the drug. The synthetic strategy involves in situ generation of functionalized arylmagnesium bromide with Weinreb-amide (WA) functionality for the first time, and addition on to the 1-β-formyl-2,3,4,6-tetra-O-benzyl-D-glucopyranoside for the synthesis of a C-benzyl glucoside building block 16. The WA functionality therein enabled variation in the nature of the distal ring of biarylmethane aglycon for convenient access to other analogues. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using cell-based nonradioactive fluorescence glucose uptake assay. Among them, 14 with IC50: 0.64 nm emerged as the most potent SGLT2 inhibitor with the best selectivity for inhibition of SGLT2 (IC50:0.64 nm) over SGLT1 (IC50: 500 nm) as compare to Dapagliflozin. On the other hand, compound 15a exhibited moderate selectivity for inhibition of SGLT2 (IC50: 4.94 nm) over SGLT1 (IC50: 68.46 nm). These results presented herein amply demonstrate the promise of C-benzyl analogues of Dapagliflozin as novel SGLT2 inhibitors for future investigations.
Synthesis method of 2-halogen-5-iodobenzoic acid
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Paragraph 0031-0041, (2019/09/17)
The invention discloses a synthesis method of 2-halogen-5-iodobenzoic acid. The synthesis method comprises steps as follows: o-halogen benzoic acids are subjected to one-step iodo treatment in an iodio reagent, and 2-halogen-5-iodobenzoic acid is obtained. Aftertreatment comprises steps as follows: a reaction liquid is poured into a cold reductive water solution and quenched, a solvent is evaporated to dryness, recrystallization and filtration are performed, and a product can be obtained. The method is short in reaction route, simple to operate, environmentally friendly, safer and more economical and has broad application prospects.
Late stage iodination of biologically active agents using a one-pot process from aryl amines
Sloan, Nikki L.,Luthra, Sajinder K.,McRobbie, Graeme,Pimlott, Sally L.,Sutherland, Andrew
, p. 54881 - 54891 (2017/12/12)
A simple and effective one-pot tandem procedure that generates aryl iodides from readily available aryl amines via stable diazonium salts has been developed. The operationally simple procedure and mild conditions allow late-stage iodination of a wide range of aryl compounds bearing various functional groups and substitution patterns. A novel synthetic strategy involving the preparation of nitroaryl compounds followed by a chemoselective tin(ii) dichloride reduction and the use of the one-pot diazotisation-iodination transformation was also developed. The general applicability of this approach was demonstrated with the preparation of a number of medicinally important compounds including CNS1261, a SPECT imaging agent of the N-methyl-d-aspartate (NMDA) receptor and IBOX, a compound used to detect amyloid plaques in the brain.