7NEE

Inhibitor Complex with Thrombin Activatable Fibrinolysis inhibitor (TAFIa)

Summary for 7NEE

• Entry DOI: 10.2210/pdb7nee/pdb
• Descriptor: Carboxypeptidase B2, (1R,3S)-3-(4-ammoniobutyl)-1-benzyl-1,4-azaphosphinan-1-ium-3-carboxylate 4,4-dioxide, ZINC ION, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 46340.78

Authors

Brown, D.G.,Schaffner, A.P.,Gloanec, P.,Raimbaud, E.,Vuillard, L.M. (deposition date: 2021-02-03, release date: 2021-04-07, Last modification date: 2024-11-20)

Primary citation

Schaffner, A.P.,Sansilvestri-Morel, P.,Despaux, N.,Ruano, E.,Persigand, T.,Rupin, A.,Mennecier, P.,Vallez, M.O.,Raimbaud, E.,Desos, P.,Gloanec, P.
Phosphinanes and Azaphosphinanes as Potent and Selective Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa).
J.Med.Chem., 64:3897-3910, 2021

PubMed Abstract: Selective and potent inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) have the potential to increase endogenous and therapeutic fibrinolysis and to behave like profibrinolytic agents without the risk of major hemorrhage, since they do not interfere either with platelet activation or with coagulation during blood hemostasis. Therefore, TAFIa inhibitors could be used in at-risk patients for the treatment, prevention, and secondary prevention of stroke, venous thrombosis, and pulmonary embolisms. In this paper, we describe the design, the structure-activity relationship (SAR), and the synthesis of novel, potent, and selective phosphinanes and azaphosphinanes as TAFIa inhibitors. Several highly active azaphosphinanes display attractive properties suitable for further efficacy studies in thrombosis models.

PubMed: 33764059
DOI: 10.1021/acs.jmedchem.0c02072

Experimental method

X-RAY DIFFRACTION (2.55 Å)