1-Aminomethylisoquinoline-4-carboxylates as novel dipeptidylpeptidase IV inhibitors.
Structure-activity relationship within a series of 1-aminoalkylisoquinoline-4-carboxylates as inhibitors of DPP-IV is described. A primary aminomethyl group is required to maintain biological activity. Substitution of the isoquinoline at the 6- and 8-positions with methoxy groups increases potency to 53 times that of the lead compound SDZ 029-576.
Metabolic and Cardiovascular Diseases Research, Novartis Institute for Biomedical Research, Summit, NJ 07901, USA. gary.coppola@pharm.novartis.com
G M
GM
Coppola
Y L
YL
Zhang
H F
HF
Schuster
M E
ME
Russell
T E
TE
Hughes
D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003110:Colonic Neoplasms; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D002264:Carboxylic Acids; D007202:Indicators and Reagents; D007546:Isoquinolines; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4