title: 1,3-disubstituted 4-aminopiperidines as useful tools in the optimization of the 2-aminobenzo[a]quinolizine dipeptidyl peptidase IV inhibitors.
abstract: In a search for novel DPP-IV inhibitors, 2-aminobenzo[a]quinolizines were identified as submicromolar HTS hits. Due to the difficult synthetic access to this compound class, 1,3-disubstituted 4-aminopiperidines were used as model compounds for optimization. The developed synthetic methodology and the SAR could be transferred to the 2-aminobenzo[a]quinolizine series, leading to highly active DPP-IV inhibitors.
authors.affiliation: Discovery Research, Pharmaceutical Division, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. thomas.luebbers@roche.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Lübbers
authors.forename: Markus
authors.initials: M
authors.lastname: Böhringer
authors.forename: Luca
authors.initials: L
authors.lastname: Gobbi
authors.forename: Michael
authors.initials: M
authors.lastname: Hennig
authors.forename: Daniel
authors.initials: D
authors.lastname: Hunziker
authors.forename: Bernd
authors.initials: B
authors.lastname: Kuhn
authors.forename: Bernd
authors.initials: B
authors.lastname: Löffler
authors.forename: Patrizio
authors.initials: P
authors.lastname: Mattei
authors.forename: Robert
authors.initials: R
authors.lastname: Narquizian
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Peters
authors.forename: Yves
authors.initials: Y
authors.lastname: Ruff
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Wessel
authors.forename: Pierre
authors.initials: P
authors.lastname: Wyss
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry; D058892:Adenosine Deaminase Inhibitors; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D058892:Adenosine Deaminase Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins; D010880:Piperidines; D011480:Protease Inhibitors; C034628:N-aminopiperidine; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase