Xanthine mimetics as potent dipeptidyl peptidase IV inhibitors.
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.
Kurukulasuriya
Ravi
R
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA. ravi.kurukulasuriya@abbott.com
Rohde
Jeffrey J
JJ
Szczepankiewicz
Bruce G
BG
Basha
Fatima
F
Lai
Chunqui
C
Jae
Hwan-Soo
HS
Winn
Martin
M
Stewart
Kent D
KD
Longenecker
Kenton L
KL
Lubben
Thomas W
TW
Ballaron
Stephen J
SJ
Sham
Hing L
HL
von Geldern
Thomas W
TW
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*
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007093:Imidazoles; D011480:Protease Inhibitors; D014970:Xanthines; D018819:Dipeptidyl Peptidase 4