Rational design, synthesis, and structure-activity relationships of 5-amino-1H-pyrazole-4-carboxylic acid derivatives as protein tyrosine phosphatase 1B inhibitors.
A series of novel amino-carboxylic based pyrazole as protein tyrosine phosphatase 1B (PTP1B) inhibitors were designed on the basis of structure-based pharmacophore model and molecular docking. Compounds containing different hydrophobic tail (1,2-diphenyl ethanone, oxdiadizole and dibenzyl amines) were synthesized and evaluated in PTP1B enzymatic assay. Structure-activity relationship based optimization resulted in identification of several potent, metabolically stable and cell permeable PTP1B inhibitors.
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India. Electronic address: sujay.basu@advinus.com.
Sujay
S
Basu
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Philip
P
Prathipati
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Sachin
S
Thorat
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Shariq
S
Ansari
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Meena
M
Patel
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Vaibhav
V
Jain
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Ramana R
RR
Jinugu
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Sanjay
S
Niranjan
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Siddhartha
S
De
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Phase-I, MIDC, Hinjewadi, Pune 411 057, India.
Satyanarayana
S
Reddy
D000586:Amination; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
Hydrophobic; Oxadiazole; Permeability; Pharmacophore; Protein tyrosine phosphatase 1B