title: Synthesis and antidiabetic performance of β-amino ketone containing nabumetone moiety.
abstract: We wish to report the further design and improved synthesis that resulted in two series of target molecules, TM-1 and TM-2, with remarkably simplified structures containing β-amino ketone of discrete nabumetone moiety. These were obtained via a 'one-pot, two-step, three-component' protocol of Mannich reaction with yield up to 97%. A total of 28 out of 31 new compounds were characterized using (1)H NMR, (13)C NMR, ESI MS and HRMS techniques. Studies on their antidiabetic activities, screened in vitro at 10 μg mL(-1) level, indicate that TM-2 possesses peroxisome proliferator-activated receptor activation and α-glucosidase inhibition activity significantly stronger than that of TM-1, and also that of the series B compounds that were previously synthesized by the group. Analysis of the structure-activity relationship points to the sulfanilamide unit as the most probable potent group of β-amino ketone and, on the basis of which, a tangible strategy is presented for the development of new antidiabetic drugs.
authors.affiliation: School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.forename: Ju-fang
authors.initials: JF
authors.lastname: Yan
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Guang-ming
authors.initials: GM
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Da-cheng
authors.initials: DC
authors.lastname: Yang
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002074:Butanones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D000077430:Nabumetone; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism; D013329:Structure-Activity Relationship; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D000588:Amines; D002074:Butanones; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D007659:Ketones; D047492:Peroxisome Proliferator-Activated Receptors; D013424:Sulfanilamides; D000077145:Sulfanilamide; D000520:alpha-Glucosidases; D000077430:Nabumetone