Biomaterial Database

Aryl- and heteroaryl-substituted aminobenzo[a]quinolizines as dipeptidyl peptidase IV inhibitors. 2010

Markus Boehringer, and Holger Fischer, and Michael Hennig, and Daniel Hunziker, and Joerg Huwyler, and Bernd Kuhn, and Bernd M Loeffler, and Thomas Luebbers, and Patrizio Mattei, and Robert Narquizian, and Elena Sebokova, and Urs Sprecher, and Hans Peter Wessel

F Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland.

Synthesis and SAR are described for a structurally distinct class of DPP-IV inhibitors based on aminobenzo[a]quinolizines bearing (hetero-)aromatic substituents in the S1 specificity pocket. The m-(fluoromethyl)-phenyl derivative (S,S,S)-2g possesses the best fit in the S1 pocket. However, (S,S,S)-2i, bearing a more hydrophilic 5-methyl-pyridin-2-yl residue as substituent for the S1 pocket, displays excellent in vivo activity and superior drug-like properties.

UI	MeSH Term	Description	Entries
D011480	Protease Inhibitors	Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).	Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D011807	Quinolizines
D011924	Rats, Zucker	Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene.	Zucker Rat,Zucker Rats,Rat, Zucker
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D054873	Dipeptidyl-Peptidase IV Inhibitors	Compounds that suppress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release.	DPP-4 Inhibitor,DPP-4 Inhibitors,DPP-IV Inhibitor,DPP-IV Inhibitors,DPP4 Inhibitor,DPP4 Inhibitors,Dipeptidyl Peptidase 4 Inhibitor,Dipeptidyl-Peptidase 4 Inhibitor,Dipeptidyl-Peptidase IV Inhibitor,Gliptin,Gliptins,Dipeptidyl-Peptidase 4 Inhibitors,DPP 4 Inhibitor,DPP 4 Inhibitors,DPP IV Inhibitor,DPP IV Inhibitors,Dipeptidyl Peptidase 4 Inhibitors,Dipeptidyl Peptidase IV Inhibitor,Dipeptidyl Peptidase IV Inhibitors,Inhibitor, DPP-4,Inhibitor, DPP-IV,Inhibitor, DPP4,Inhibitor, Dipeptidyl-Peptidase 4,Inhibitor, Dipeptidyl-Peptidase IV
D018360	Crystallography, X-Ray	The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D018819	Dipeptidyl Peptidase 4	A serine protease that catalyses the release of an N-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including INCRETINS; NEUROPEPTIDES; and CHEMOKINES. The protein is also found bound to ADENOSINE DEAMINASE on the T-CELL surface and is believed to play a role in T-cell activation.	Antigens, CD26,CD26 Antigens,Dipeptidyl-Peptidase IV,Adenosine Deaminase Complexing Protein 2,CD26 Antigen,Antigen, CD26,Dipeptidyl Peptidase IV