Synthesis of novel l-rhamnose derived acyclic C-nucleosides with substituted 1,2,3-triazole core as potent sodium-glucose co-transporter (SGLT) inhibitors

Siddamal Reddy Putapatri, Abhinav Kanwal, Sanjay K. Banerjee, Srinivas Kantevari

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes by preventing renal glucose reabsorption. In our efforts to identify novel inhibitors of SGLT, we synthesized a series of l-rhamnose derived acyclic C-nucleosides with 1,2,3-triazole core. The key β-ketoester building block 4 prepared from l-rhamnose in five steps, was reacted with various aryl azides to produce the respective 1,2,3-triazole derivatives in excellent yields. Deprotection of acetonide group gave the desired acyclic C-nucleosides 7a-o. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using recently developed cell-based nonradioactive fluorescence glucose uptake assay. Among them, 7m with IC50: 125.9 nM emerged as the most potent SGLT2 inhibitor. On the other hand compound 7d exhibited best selectivity for inhibition of SGLT2 (IC50: 149.1 nM) over SGLT1 (IC50: 693.2 nM). The results presented here demonstrated the utility of acyclic C-nucleosides as novel SGLT inhibitors for future investigations.

Original languageEnglish
Pages (from-to)1528-1531
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number6
DOIs
Publication statusPublished - 15-03-2014

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Sodium-Glucose Transport Proteins
Symporters
Rhamnose
Triazoles
Nucleosides
Sodium
Inhibitory Concentration 50
Glucose
Azides
Type 2 Diabetes Mellitus
Fluorescence
Medical problems
Assays
Derivatives

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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title = "Synthesis of novel l-rhamnose derived acyclic C-nucleosides with substituted 1,2,3-triazole core as potent sodium-glucose co-transporter (SGLT) inhibitors",
abstract = "Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes by preventing renal glucose reabsorption. In our efforts to identify novel inhibitors of SGLT, we synthesized a series of l-rhamnose derived acyclic C-nucleosides with 1,2,3-triazole core. The key β-ketoester building block 4 prepared from l-rhamnose in five steps, was reacted with various aryl azides to produce the respective 1,2,3-triazole derivatives in excellent yields. Deprotection of acetonide group gave the desired acyclic C-nucleosides 7a-o. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using recently developed cell-based nonradioactive fluorescence glucose uptake assay. Among them, 7m with IC50: 125.9 nM emerged as the most potent SGLT2 inhibitor. On the other hand compound 7d exhibited best selectivity for inhibition of SGLT2 (IC50: 149.1 nM) over SGLT1 (IC50: 693.2 nM). The results presented here demonstrated the utility of acyclic C-nucleosides as novel SGLT inhibitors for future investigations.",
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Synthesis of novel l-rhamnose derived acyclic C-nucleosides with substituted 1,2,3-triazole core as potent sodium-glucose co-transporter (SGLT) inhibitors. / Putapatri, Siddamal Reddy; Kanwal, Abhinav; Banerjee, Sanjay K.; Kantevari, Srinivas.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 6, 15.03.2014, p. 1528-1531.

Research output: Contribution to journalArticle

TY - JOUR

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