4F08

Discovery and Optimization of C-2 Methyl Imidazo-pyrrolopyridines as Potent and Orally Bioavailable JAK1 Inhibitors with Selectivity over JAK2

Experimental procedure

Experimental method	SINGLE
Source type	SYNCHROTRON
Source details	ALS BEAMLINE 5.0.1
Synchrotron site	ALS
Beamline	5.0.1
Temperature [K]	100
Detector technology	CCD
Collection date	2010-04-16
Detector	ADSC QUANTUM 4
Wavelength(s)	1.0
Spacegroup name	P 41
Unit cell lengths	110.923, 110.923, 70.732
Unit cell angles	90.00, 90.00, 90.00

Refinement procedure

Resolution	49.610 - 2.820
R-factor	0.2145
Rwork	0.213
R-free	0.24100
Structure solution method	MOLECULAR REPLACEMENT
Starting model (for MR)	2b7a
Data reduction software	DENZO
Data scaling software	SCALEPACK
Phasing software	PHASER
Refinement software	BUSTER-TNT

Data quality characteristics

	Overall	Inner shell	Outer shell
Low resolution limit [Å]	50.000	50.000	2.920
High resolution limit [Å]	2.820	6.070	2.820
Rmerge	0.102	0.034	0.518
Number of reflections	20873
<I/σ(I)>	9.2
Completeness [%]	99.8	100	98.3
Redundancy	5	4.9	4.4

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	VAPOR DIFFUSION, HANGING DROP	6	277	0.2 M ammonium acetate, 0.1M sodium citrate pH6, 25% PEG 8000, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 277K