Design, synthesis and docking studies on phenoxy-3-piperazin-1-yl-propan-2-ol derivatives as protein tyrosine phosphatase 1B inhibitors.
A series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols has been synthesized and evaluated for PTP1B inhibitory activity in vitro and for antidiabetic activity in vivo. Two molecules viz. 4a and 5b showed PTP1B inhibition of 31.58% and 35.90% at 100 μM concentration. The compound 4a also showed 40.3% normalization of plasma glucose levels at 100mg/kg in Sugar-loaded model (SLM) and 32% activity in Streptozodocin model (STZ). The docking studies of these molecules revealed that hydrogen bond formation with Arg221 is important for activity.
Gupta
Swati
S
Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow 226001, India.
Pandey
Gyanendra
G
Rahuja
Neha
N
Srivastava
Arvind K
AK
Saxena
Anil K
AK
D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004195:Disease Models, Animal; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D020005:Propanols / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D010879:Piperazines; D020005:Propanols; D000077489:Piperazine; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1