3R4O

Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide

Experimental procedure

Experimental method	SINGLE WAVELENGTH
Source type	ROTATING ANODE
Source details	RIGAKU
Temperature [K]	98
Detector technology	IMAGE PLATE
Collection date	2007-04-15
Detector	MAR scanner 345 mm plate
Wavelength(s)	1.5418
Spacegroup name	P 21 21 21
Unit cell lengths	43.149, 79.523, 130.101
Unit cell angles	90.00, 90.00, 90.00

Refinement procedure

Resolution	19.880 - 2.650
R-factor	0.215
Rwork	0.211
R-free	0.28500
Structure solution method	MOLECULAR REPLACEMENT
RMSD bond length	0.006
RMSD bond angle	0.900
Data reduction software	HKL-2000
Data scaling software	SCALEPACK
Phasing software	CNX
Refinement software	CNX

Data quality characteristics

	Overall	Outer shell
Low resolution limit [Å]	19.880	2.740
High resolution limit [Å]	2.650	2.650
Rmerge	0.074	0.211
Number of reflections	11758
<I/σ(I)>	18.4	6.45
Completeness [%]	86.2	79.6
Redundancy	4.7	4.3

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	VAPOR DIFFUSION, HANGING DROP	4.5	286	5 % Ethylene glycol, 0.1 M phosphate-citrate, pH 4.5, 20 mM TCEP, VAPOR DIFFUSION, HANGING DROP, temperature 286K