5TNT

Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors

Summary for 5TNT

• Entry DOI: 10.2210/pdb5tnt/pdb
• Related: 5TNO
• Descriptor: Coagulation factor IX, N-[(1S,4S,7R)-2-(3-amino-4-chloro[1,2]oxazolo[5,4-c]pyridin-7-yl)-2-azabicyclo[2.2.1]heptan-7-yl]-2-chloro-4-(3-methyl-1H-1,2,4-triazol-1-yl)benzamide, SODIUM ION, ... (6 entities in total)
• Functional Keywords: serine proteinase, blood coagulation, coagulation factor, hydrolase-2, hydrolase inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted : P00740 P00740
• Total number of polymer chains: 2
• Total formula weight: 33676.15

Authors

Sakurada, I.,Endo, T.,Hikita, K.,Hirabayashi, T.,Hosaka, Y.,Kato, Y.,Maeda, Y.,Matsumoto, S.,Mizuno, T.,Nagasue, A.,Nishimura, T.,Shimada, S.,Shinozaki, M.,Taguchi, K.,Takeuchi, K.,Yokoyama, T.,Hruza, A.,Reichert, P.,Zhang, T.,Wood, H.B.,Nakao, K.,Furusako, S. (deposition date: 2016-10-14, release date: 2017-04-26, Last modification date: 2024-10-30)

Primary citation

Sakurada, I.,Endo, T.,Hikita, K.,Hirabayashi, T.,Hosaka, Y.,Kato, Y.,Maeda, Y.,Matsumoto, S.,Mizuno, T.,Nagasue, H.,Nishimura, T.,Shimada, S.,Shinozaki, M.,Taguchi, K.,Takeuchi, K.,Yokoyama, T.,Hruza, A.,Reichert, P.,Zhang, T.,Wood, H.B.,Nakao, K.,Furusako, S.
Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors.
Bioorg. Med. Chem. Lett., 27:2622-2628, 2017

PubMed Abstract: Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated.

PubMed: 28408226
DOI: 10.1016/j.bmcl.2017.03.002

Experimental method

X-RAY DIFFRACTION (1.4 Å)