5VP1

Discovery of Clinical Candidate N-{(1S)-1-[3-Fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915), A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders

Experimental procedure

Experimental method	SINGLE WAVELENGTH
Source type	SYNCHROTRON
Source details	ALS BEAMLINE 5.0.2
Synchrotron site	ALS
Beamline	5.0.2
Temperature [K]	100
Detector technology	PIXEL
Collection date	2016-03-03
Detector	DECTRIS PILATUS3 S 6M
Wavelength(s)	1.000
Spacegroup name	C 1 2 1
Unit cell lengths	165.129, 72.712, 90.061
Unit cell angles	90.00, 109.15, 90.00

Refinement procedure

Resolution	30.000 - 1.860
R-factor	0.2254
Rwork	0.225
R-free	0.24330
Structure solution method	MOLECULAR REPLACEMENT
RMSD bond length	0.008
RMSD bond angle	1.243
Data reduction software	HKL-2000
Data scaling software	Aimless (0.5.21)
Phasing software	PHASER
Refinement software	REFMAC (5.8.0135)

Data quality characteristics

	Overall	Inner shell	Outer shell
Low resolution limit [Å]	30.000	30.000	1.900
High resolution limit [Å]	1.860	8.300	1.860
Rmerge	0.057	0.018	1.009
Rmeas	0.078	0.025	1.383
Total number of observations	269612
Number of reflections	80761	1679	10129
<I/σ(I)>	8.4	28.27	0.84
Completeness [%]	86.1	89.5	81.4
Redundancy	1.871	1.787	1.79
CC(1/2)	0.998	0.999	0.543

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	VAPOR DIFFUSION, HANGING DROP	7.5	293	30% PEG3350, 0.2M MgCl2, 0.1M Tris pH 7.5