8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes.
A new chemical class of potent DPP-4 inhibitors structurally derived from the xanthine scaffold for the treatment of type 2 diabetes has been discovered and evaluated. Systematic structural variations have led to 1 (BI 1356), a highly potent, selective, long-acting, and orally active DPP-4 inhibitor that shows considerable blood glucose lowering in different animal species. 1 is currently undergoing clinical phase IIb trials and holds the potential for once-daily treatment of type 2 diabetics.
Eckhardt
Matthias
M
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. matthias.eckhardt@boehringer-ingelheim.com
Langkopf
Elke
E
Mark
Michael
M
Tadayyon
Moh
M
Thomas
Leo
L
Nar
Herbert
H
Pfrengle
Waldemar
W
Guth
Brian
B
Lotz
Ralf
R
Sieger
Peter
P
Fuchs
Holger
H
Himmelsbach
Frank
F
D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D018360:Crystallography, X-Ray; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004285:Dogs; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000069476:Linagliptin; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010880:Piperidines; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4