3SW2: X-Ray Crystal Structure Of Human Fxa In Complex With 6-Chloro-N-((3s)- 2-Oxo-1-(2-Oxo-2-((5s)-8-Oxo-5,6-Dihydro-1h-1,5-Methanopyrido[1,2- A][1,5]diazocin-3(2h,4h,8h)-Yl)ethyl)piperidin-3-Yl)naphthalene-2- Sulfonamide

Citation:
Abstract
The design, synthesis and SAR of a novel class of valerolactam-based arylsulfonamides as potent and selective FXa inhibitors is reported. The arylsulfonamide-valerolactam scaffold was derived based on the proposed bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in this series, with an IC(50) of 7nM and EC(2xPT) of 1.7muM. The X-ray structure of compound 40 bound to FXa shows that the sulfonamide-valerolactam scaffold anchors the aryl group in the S1 and the novel acylcytisine pharmacophore in the S4 pockets.
PDB ID: 3SW2Download
MMDB ID: 95060
PDB Deposition Date: 2011/7/13
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 2.42  Å
Source Organism:
Similar Structures:
Biological Unit for 3SW2: dimeric; determined by author and by software (PISA)
Molecular Components in 3SW2
Label Count Molecule
Proteins (2 molecules)
1
Coagulation Factor X(Gene symbol: F10)
Molecule annotation
1
Coagulation Factor X(Gene symbol: F10)
Molecule annotation
Chemicals (4 molecules)
1
1
2
1
3
1
4
1
* Click molecule labels to explore molecular sequence information.

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