1,3-disubstituted 4-aminopiperidines as useful tools in the optimization of the 2-aminobenzo[a]quinolizine dipeptidyl peptidase IV inhibitors.
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.
Lübbers
Thomas
T
Discovery Research, Pharmaceutical Division, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. thomas.luebbers@roche.com
Böhringer
Markus
M
Gobbi
Luca
L
Hennig
Michael
M
Hunziker
Daniel
D
Kuhn
Bernd
B
Löffler
Bernd
B
Mattei
Patrizio
P
Narquizian
Robert
R
Peters
Jens-Uwe
JU
Ruff
Yves
Y
Wessel
Hans Peter
HP
Wyss
Pierre
P
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
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