My watch list
my.chemeurope.com  
Login  

Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation

Publication date:

October 2018


Source:Bioorganic Chemistry, Volume 80

Author(s): Neelesh Maheshwari, Chandrabose Karthikeyan, Shraddha V. Bhadada, Chandan Sahi, Amit K. Verma, N.S. Hari Narayana Moorthy, Piyush Trivedi

Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC50 value of 4.48 µM. Docking studies with NM-03 revealed the key interactions with desired amino acids in the binding site of PTP1B. Furthermore, compound NM-03 also elicited good in vivo activity. Taken together, the results of this study establish N-(3-(1H-tetrazole-5-yl)phenyl)-2-(benzo[d]oxazol-2-ylthio)acetamide (NM-03) as a valuable lead molecule with great potential for PTP1B inhibitor development targeting diabetes.
Graphical abstract




Authors:   Author(s): Neelesh Maheshwari, Chandrabose Karthikeyan, Shraddha V. Bhadada, Chandan Sahi, Amit K. Verma, N.S. Hari Narayana Moorthy, Piyush Trivedi
Journal:   Bioorganic Chemistry
Volume:   80
Year:   2018
Pages:   145
DOI:   10.1016/j.bioorg.2018.06.016
Publication date:   25-Jun-2018
Facts, background information, dossiers
More about Elsevier
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE