5TNT

Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.161 
  • R-Value Work: 0.146 
  • R-Value Observed: 0.147 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors.

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.

(2017) Bioorg Med Chem Lett 27: 2622-2628

  • DOI: https://doi.org/10.1016/j.bmcl.2017.03.002
  • Primary Citation of Related Structures:  
    5TNO, 5TNT

  • 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.


  • Organizational Affiliation

    Discovery Research, Mochida Pharmaceutical Co. Ltd., 722 Uenohara, Jimba, Gotemba, Shizuoka 412-8524, Japan. Electronic address: isao.sakurada@mochida.co.jp.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor IX235Homo sapiensMutation(s): 1 
Gene Names: F9
EC: 3.4.21.22
UniProt & NIH Common Fund Data Resources
Find proteins for P00740 (Homo sapiens)
Explore P00740 
Go to UniProtKB:  P00740
PHAROS:  P00740
GTEx:  ENSG00000101981 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00740
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor IX62Homo sapiensMutation(s): 0 
Gene Names: F9
EC: 3.4.21.22
UniProt & NIH Common Fund Data Resources
Find proteins for P00740 (Homo sapiens)
Explore P00740 
Go to UniProtKB:  P00740
PHAROS:  P00740
GTEx:  ENSG00000101981 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00740
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7GQ
Query on 7GQ

Download Ideal Coordinates CCD File 
C [auth A]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
C22 H20 Cl2 N8 O2
KWAYYBDVPSPGPN-SDDDUWNISA-N
NHE
Query on NHE

Download Ideal Coordinates CCD File 
E [auth A]2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID
C8 H17 N O3 S
MKWKNSIESPFAQN-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
D [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
7GQ BindingDB:  5TNT IC50: min: 100, max: 550 (nM) from 2 assay(s)
Binding MOAD:  5TNT IC50: 4.9 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.161 
  • R-Value Work: 0.146 
  • R-Value Observed: 0.147 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.084α = 90
b = 99.084β = 90
c = 94.68γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
autoPROCdata scaling
XDSdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2017-04-26
    Type: Initial release
  • Version 1.1: 2017-05-24
    Changes: Database references
  • Version 1.2: 2017-11-22
    Changes: Refinement description
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description