An aminomethylpyrimidine DPP-IV inhibitor with improved properties.
A recently identified DPP-IV inhibitor (1) was found to induce phospholipidosis and to inhibit CYP3A4. A small series of less lipophilic and less amphiphilic analogues was synthesized in an effort to overcome these issues. One compound from this series was equipotent to 1, did not induce phospholipidosis and showed a reduced CYP3A4 inhibition.
Peters
Jens-Uwe
JU
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. jens-uwe.peters@roche.com
Hunziker
Daniel
D
Fischer
Holger
H
Kansy
Manfred
M
Weber
Silja
S
Kritter
Stéphane
S
Müller
Aranka
A
Wallier
Angelina
A
Ricklin
Fabienne
F
Boehringer
Markus
M
Poli
Sonia Maria
SM
Csato
Miklos
M
Loeffler
Bernd-Michael
BM
D000588:Amines / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D008064:Lipidoses / Q000188:drug therapy; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000588:Amines; D065607:Cytochrome P-450 Enzyme Inhibitors; D011480:Protease Inhibitors; D011743:Pyrimidines; C495751:aminomethylpyrimidine; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D018819:Dipeptidyl Peptidase 4