title: Xanthine mimetics as potent dipeptidyl peptidase IV inhibitors.
abstract: A series of xanthine mimetics containing 5,5 and 5,6 heterocycle fused imidazoles were synthesized as dipeptidyl peptidase IV inhibitors. Compound 7 is potent (h-DPPIV K(i)=2nM) and exhibits excellent selectivity and no species specificity against rat and human enzymes. The X-ray structure confirms that the binding mode of 7 to rat DPPIV is similar to the parent xanthines.
authors.affiliation: Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA. ravi.kurukulasuriya@abbott.com
authors.forename: Ravi
authors.initials: R
authors.lastname: Kurukulasuriya
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Rohde
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Szczepankiewicz
authors.forename: Fatima
authors.initials: F
authors.lastname: Basha
authors.forename: Chunqui
authors.initials: C
authors.lastname: Lai
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Jae
authors.forename: Martin
authors.initials: M
authors.lastname: Winn
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
authors.forename: Kenton L
authors.initials: KL
authors.lastname: Longenecker
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Lubben
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ballaron
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Thomas W
authors.initials: TW
authors.lastname: von Geldern
mesh_terms: D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction; D014970:Xanthines / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007093:Imidazoles; D011480:Protease Inhibitors; D014970:Xanthines; D018819:Dipeptidyl Peptidase 4