title: An aminomethylpyrimidine DPP-IV inhibitor with improved properties.
abstract: 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.
authors.affiliation: Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. jens-uwe.peters@roche.com
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Peters
authors.forename: Daniel
authors.initials: D
authors.lastname: Hunziker
authors.forename: Holger
authors.initials: H
authors.lastname: Fischer
authors.forename: Manfred
authors.initials: M
authors.lastname: Kansy
authors.forename: Silja
authors.initials: S
authors.lastname: Weber
authors.forename: Stéphane
authors.initials: S
authors.lastname: Kritter
authors.forename: Aranka
authors.initials: A
authors.lastname: Müller
authors.forename: Angelina
authors.initials: A
authors.lastname: Wallier
authors.forename: Fabienne
authors.initials: F
authors.lastname: Ricklin
authors.forename: Markus
authors.initials: M
authors.lastname: Boehringer
authors.forename: Sonia Maria
authors.initials: SM
authors.lastname: Poli
authors.forename: Miklos
authors.initials: M
authors.lastname: Csato
authors.forename: Bernd-Michael
authors.initials: BM
authors.lastname: Loeffler
mesh_terms: 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
chemical_list: 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