Design and synthesis of 2,4-disubstituted polyhydroquinolines as prospective antihyperglycemic and lipid modulating agents.
A series of 2,4-disubstituted polyhydroquinoline were synthesized and evaluated for their in vivo antihyperglycemic as well as antidyslipidemic activities. Several synthesized compounds have exhibited promising in vivo antihyperglycemic in SLM, STZ-S, and db/db mice model along with significant lipid and TG modulating activity. All these compounds were evaluated in various in vitro models of diabetes to know the possible mechanism of their antihyperglycemic action. Interestingly, compounds 3a-r (diaryl substitution) have exhibited promising protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity whereas, compounds 5a-d (acid substituted) have shown significant glycogen phosphorylase activity.
Kumar
Atul
A
Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226 001, India. dratulsax@gmail.com
Sharma
Siddharth
S
Tripathi
Vishwa Deepak
VD
Maurya
Ram Awatar
RA
Srivastava
Swayam Prakash
SP
Bhatia
Gitika
G
Tamrakar
A K
AK
Srivastava
Arvind Kumar
AK
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D015195:Drug Design; D050171:Dyslipidemias / Q000188:drug therapy*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology
D007004:Hypoglycemic Agents; D011804:Quinolines; D024981:Glycogen Phosphorylase; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse