4P10

pro-carboxypeptidase U In Complex With 5-(3-aminopropyl)-1-propyl-6,7-dihydro-4H-benzimidazole-5-carboxylic acid

Summary for 4P10

• Entry DOI: 10.2210/pdb4p10/pdb
• Descriptor: Carboxypeptidase B2, (5R)-5-(3-aminopropyl)-1-propyl-4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid, ZINC ION, ... (6 entities in total)
• Functional Keywords: inhibitor, drug discovery, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 47009.49

Authors

Hallberg, K.,Sjogren, T. (deposition date: 2014-02-21, release date: 2014-08-13, Last modification date: 2024-10-09)

Primary citation

Brink, M.,Dahlen, A.,Olsson, T.,Polla, M.,Svensson, T.
Design and synthesis of conformationally restricted inhibitors of active thrombin activatable fibrinolysis inhibitor (TAFIa).
Bioorg.Med.Chem., 22:2261-2268, 2014

PubMed Abstract: A series of 4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid and 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid derivatives designed as inhibitors of TAFIa has been prepared via a common hydrogenation-alkylation sequence starting from the appropriate benzimidazole and imidazopyridine system. We present a successful design strategy using a conformational restriction approach resulting in potent and selective inhibitors of TAFIa. The X-ray structure of compound 5 in complex with a H333Y/H335Q double mutant TAFI indicate that the conformational restriction is responsible for the observed potency increase.

PubMed: 24588961
DOI: 10.1016/j.bmc.2014.02.010

Experimental method

X-RAY DIFFRACTION (2 Å)