title: Design and synthesis of 2,4-disubstituted polyhydroquinolines as prospective antihyperglycemic and lipid modulating agents.
abstract: 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.
authors.affiliation: Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226 001, India. dratulsax@gmail.com
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.forename: Siddharth
authors.initials: S
authors.lastname: Sharma
authors.forename: Vishwa Deepak
authors.initials: VD
authors.lastname: Tripathi
authors.forename: Ram Awatar
authors.initials: RA
authors.lastname: Maurya
authors.forename: Swayam Prakash
authors.initials: SP
authors.lastname: Srivastava
authors.forename: Gitika
authors.initials: G
authors.lastname: Bhatia
authors.forename: A K
authors.initials: AK
authors.lastname: Tamrakar
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: 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
chemical_list: D007004:Hypoglycemic Agents; D011804:Quinolines; D024981:Glycogen Phosphorylase; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse