Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S
Lategahn, Jonas; Keul, Marina; Klövekorn, Philip; Tumbrink, Hannah L.; Niggenaber, Janina; Müller, Matthias P.; Hodson, Luke; Flaßhoff, Maren; Hardick, Julia; Grabe, Tobias; Engel, Julian; Schultz-Fademrecht, Carsten; Baumann, Matthias; Ketzer, Julia; Mühlenberg, Thomas; Hiller, Wolf; Günther, Georgia; Unger, Anke; Müller, Heiko; Heimsoeth, Alena; Golz, Christopher; Blank-Landeshammer, Bernhard; Kollipara, Laxmikanth; Zahedi, René P.; Strohmann, Carsten; Hengstler, Jan G.; van Otterlo, Willem A. L.; Bauer, Sebastian; Rauh, Daniel; Chemical Science  (2019) –; doi:10.1039/C9SC03445E

data_1552442
_publ_section_title
;
 Inhibition of osimertinib-resistant epidermal growth factor receptor
 EGFR-T790M/C797S
;
_journal_name_full               'Chemical Science'
_journal_paper_doi               10.1039/C9SC03445E
_journal_year                    2019
_chemical_formula_moiety         'C34 H44 N6 O3 Si'
_chemical_formula_sum            'C34 H44 N6 O3 Si'
_chemical_formula_weight         612.84
_chemical_name_systematic        28a
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2100mq
_audit_creation_date             2017-08-23
_audit_creation_method
;
Olex2 1.2
(compiled 2017.08.10 svn.r3458 for OlexSys, GUI svn.r5381)
;
_audit_update_record
;
2018-11-02 deposited with the CCDC.    2019-10-16 downloaded from the CCDC.
;
_cell_angle_alpha                98.84(3)
_cell_angle_beta                 91.06(3)
_cell_angle_gamma                106.73(3)
_cell_formula_units_Z            2
_cell_length_a                   10.380(2)
_cell_length_b                   12.351(3)
_cell_length_c                   13.352(3)
_cell_measurement_reflns_used    9968
_cell_measurement_temperature    100
_cell_measurement_theta_max      28.60
_cell_measurement_theta_min      2.27
_cell_volume                     1616.3(7)
_computing_cell_refinement       'SAINT V8.38A (?, 2016)'
_computing_data_reduction        'SAINT V8.38A (?, 2016)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'XT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100.03
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.992
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0863
_diffrn_reflns_av_unetI/netI     0.0587
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.992
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            71228
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.992
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         28.834
_diffrn_reflns_theta_min         2.518
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.117
_exptl_absorpt_correction_T_max  1.0000
_exptl_absorpt_correction_T_min  0.8377
_exptl_absorpt_correction_type   numerical
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1226 before and 0.0836 after correction. The Ratio of minimum to maximum transmission is 0.8377. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.259
_exptl_crystal_description       plate
_exptl_crystal_F_000             656
_exptl_crystal_size_max          0.219
_exptl_crystal_size_mid          0.176
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.951
_refine_diff_density_min         -0.547
_refine_diff_density_rms         0.074
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.028
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     460
_refine_ls_number_reflns         8384
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.028
_refine_ls_R_factor_all          0.1070
_refine_ls_R_factor_gt           0.0636
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0633P)^2^+2.1405P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1444
_refine_ls_wR_factor_ref         0.1678
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5794
_reflns_number_total             8384
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9sc03445e2.cif
_cod_data_source_block           mo_b0012_0m
_cod_original_cell_volume        1616.3(6)
_cod_database_code               1552442
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_max   0.994
_shelx_estimated_absorpt_t_min   0.975
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Others
 Sof(N5B)=Sof(C30B)=Sof(H30C)=Sof(H30D)=Sof(C31B)=Sof(H31C)=Sof(H31D)=
 Sof(C32B)=Sof(H32C)=Sof(H32D)=Sof(C33B)=Sof(H33C)=Sof(H33D)=1-FVAR(1)
 Sof(N5A)=Sof(C30A)=Sof(H30A)=Sof(H30B)=Sof(C31A)=Sof(H31A)=Sof(H31B)=
 Sof(C32A)=Sof(H32A)=Sof(H32B)=Sof(C33A)=Sof(H33A)=Sof(H33B)=FVAR(1)
3.a Secondary CH2 refined with riding coordinates:
 C4(H4A,H4B), C5(H5A,H5B), C6(H6A,H6B), C9(H9A,H9B), C30A(H30A,H30B),
 C30B(H30C,H30D), C31A(H31A,H31B), C31B(H31C,H31D), C32A(H32A,H32B), C32B(H32C,
 H32D), C33A(H33A,H33B), C33B(H33C,H33D)
3.b Aromatic/amide H refined with riding coordinates:
 C8(H8), C15(H15), C18(H18), C20(H20), C21(H21), C22(H22), C25(H25), C26(H26),
 C28(H28), C29(H29)
3.c Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C), C2(H2A,H2B,H2C), C3(H3A,H3B,H3C), C10(H10A,H10B,H10C),
 C34(H34A,H34B,H34C)
;
_shelx_res_checksum              7508
_olex2_submission_special_instructions 'No special instructions were received'