Potent, selective small molecule inhibitors of type III phosphatidylinositol-4-kinase alpha- but not beta-inhibit the phosphatidylinositol signaling cascade and cancer cell proliferation
Michael J. Waring; David M. Andrews; Paul F. Faulder; Vikki Flemington; Jennifer C. McKelvie; Sarita Maman; Marian Preston; Piotr Raubo; Graeme R. Robb; Karen Roberts; Rachel Rowlinson; James M. Smith; Martin E. Swarbrick; Iris Treinies; Jon J. G. Winter; Robert J. Wood; Chem.Commun. 50 (2014) 5388–; doi:10.1039/C3CC48391F

data_7112643
_publ_section_title
;
 Potent, selective small molecule inhibitors of type III
 phosphatidylinositol-4-kinase alpha- but not beta-inhibit the
 phosphatidylinositol signaling cascade and cancer cell proliferation
;
_journal_name_full               Chem.Commun.
_journal_page_first              5388
_journal_paper_doi               10.1039/C3CC48391F
_journal_volume                  50
_journal_year                    2014
_chemical_absolute_configuration ad
_chemical_compound_source        AstraZeneca
_chemical_formula_moiety         'C23 H25 N5 O4 S2, C3 H6 O, 0.5(H2 O) '
_chemical_formula_sum            'C26 H32 N5 O5.5 S2'
_chemical_formula_weight         566.68
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2013
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   7.6067(5)
_cell_length_b                   16.4862(12)
_cell_length_c                   43.712(3)
_cell_measurement_reflns_used    42714
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      25.242
_cell_measurement_theta_min      2.949
_cell_volume                     5481.7(7)
_computing_cell_refinement
;
CrystalClear-SM Expert 3.1 (Rigaku, 2013)
;
_computing_data_collection
;
CrystalClear-SM Expert 3.1 (Rigaku, 2013)
;
_computing_data_reduction
;
CrystalClear-SM Expert 3.1 (Rigaku, 2013)
;
_computing_molecular_graphics
;
Images generated using CrystalMaker: a crystal and molecular 
structures program for Mac and Windows. CrystalMaker Software Ltd, 
Oxford, England (www.crystalmaker.com)
;
_computing_publication_material  'WINGX (Farrugia, 2013)'
_computing_structure_refinement  'SHELXL-2013 (Sheldrick, 2013)'
_computing_structure_solution    'SHELXS-2013 (Sheldrick, 2013)'
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 28.5714
_diffrn_detector_type            'Rigaku HG Saturn724+ (2x2 bin mode)'
_diffrn_measured_fraction_theta_full 0.974
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device       'four-circle \k diffractometer'
_diffrn_measurement_device_type  'Rigaku AFC12 (Right)'
_diffrn_measurement_method       'profile data from \w-scans'
_diffrn_measurement_specimen_support 'MiTeGen MicroMesh'
_diffrn_radiation_collimation    'Confocal mirrors, VHF Varimax '
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0393
_diffrn_reflns_av_unetI/netI     0.0328
_diffrn_reflns_Laue_measured_fraction_full 0.974
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       52
_diffrn_reflns_limit_l_min       -52
_diffrn_reflns_number            42714
_diffrn_reflns_point_group_measured_fraction_full 0.970
_diffrn_reflns_point_group_measured_fraction_max 0.992
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.027
_diffrn_reflns_theta_min         2.949
_diffrn_source                   'Rotating Anode'
_diffrn_source_current           55.0
_diffrn_source_power             2.475
_diffrn_source_voltage           45.0
_exptl_absorpt_coefficient_mu    0.242
_exptl_absorpt_process_details
;
Jacobson, R. (1998). REQAB. Private communication to the 
Rigaku Corporation, Tokyo, Japan.
;
_exptl_crystal_colour            Colourless
_exptl_crystal_density_diffrn    1.373
_exptl_crystal_description       Plate
_exptl_crystal_F_000             2392
_exptl_crystal_size_max          0.180
_exptl_crystal_size_mid          0.070
_exptl_crystal_size_min          0.060
_refine_diff_density_max         1.392
_refine_diff_density_min         -0.552
_refine_diff_density_rms         0.073
_refine_ls_abs_structure_details
;
 Flack x determined using 3711 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.01(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.115
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     703
_refine_ls_number_reflns         9609
_refine_ls_number_restraints     675
_refine_ls_restrained_S_all      1.078
_refine_ls_R_factor_all          0.0594
_refine_ls_R_factor_gt           0.0569
_refine_ls_shift/su_max          0.083
_refine_ls_shift/su_mean         0.004
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0669P)^2^+8.5498P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1495
_refine_ls_wR_factor_ref         0.1517
_reflns_Friedel_coverage         0.762
_reflns_Friedel_fraction_full    0.965
_reflns_Friedel_fraction_max     0.988
_reflns_number_gt                9238
_reflns_number_total             9609
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c3cc48391f.txt
_cod_data_source_block           2013scas0087
_cod_depositor_comments
;

2017-03-06
Z value and formula fixed to values more according to usual
chemical conventions.                 miguel
;
_cod_original_formula_moiety     '2(C23 H25 N5 O4 S2), 2(C3 H6 O), H2 O '
_cod_original_formula_sum        'C52 H64 N10 O11 S4'
_cod_original_formula_units_Z    4
_cod_original_formula_weight     1133.37
_cod_database_code               7112643
_shelx_estimated_absorpt_t_min   0.958
_shelx_estimated_absorpt_t_max   0.986
_shelxl_version_number           2013-3
_shelx_res_checksum              4934
_shelx_hkl_checksum              84639