3KWJ

Structure of human DPP-IV with (2S,3S,11bS)-3-(3-Fluoromethyl-phenyl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ylamine

Summary for 3KWJ

• Entry DOI: 10.2210/pdb3kwj/pdb
• Related: 1NU6 1NU8 3KWF 3KWH
• Descriptor: Dipeptidyl peptidase 4 soluble form, 2-acetamido-2-deoxy-beta-D-glucopyranose, (2S,3S,11bS)-3-[3-(fluoromethyl)phenyl]-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-amine, ... (4 entities in total)
• Functional Keywords: diabetes type ii, aminopeptidase, cell membrane, disulfide bond, glycoprotein, hydrolase, membrane, protease, secreted, serine protease, signal-anchor, transmembrane
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 170550.99

Authors

Hennig, M.,Stihle, M.,Thoma, R. (deposition date: 2009-12-01, release date: 2010-09-15, Last modification date: 2024-11-27)

Primary citation

Boehringer, M.,Fischer, H.,Hennig, M.,Hunziker, D.,Huwyler, J.,Kuhn, B.,Loeffler, B.M.,Luebbers, T.,Mattei, P.,Narquizian, R.,Sebokova, E.,Sprecher, U.,Wessel, H.P.
Aryl- and heteroaryl-substituted aminobenzo[a]quinolizines as dipeptidyl peptidase IV inhibitors.
Bioorg.Med.Chem.Lett., 20:1106-1108, 2010

PubMed Abstract: 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.

PubMed: 20031408
DOI: 10.1016/j.bmcl.2009.12.025

Experimental method

X-RAY DIFFRACTION (2.8 Å)