Design, synthesis and structure-activity relationship analysis of the dibenzodiazepinone derivatives against osimertinib resistant NSCLC
Jin, Chengliu; Zhang, Zhen; Liao, Peng; Zhang, Chen; Cao, Hua; Ma, Yanlong; RSC Medicinal Chemistry  (2025) –; doi:10.1039/D5MD00759C

data_7251053
_publ_section_title
;
 Design, synthesis and structure-activity relationship analysis of the
 dibenzodiazepinone derivatives against osimertinib resistant NSCLC
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D5MD00759C
_journal_year                    2025
_chemical_formula_moiety         'I, 0.5(C2 H4 Cl2), C25 H27 F N3 O2'
_chemical_formula_sum            'C26 H29 Cl F I N3 O2'
_chemical_formula_weight         596.87
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-C 2yc'
_space_group_name_H-M_alt        'C 1 2/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2022-12-12
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2023-02-19 deposited with the CCDC.	2025-10-16 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.353(3)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   37.035(3)
_cell_length_b                   9.0602(6)
_cell_length_c                   15.6080(11)
_cell_measurement_reflns_used    4905
_cell_measurement_temperature    150
_cell_measurement_theta_max      26.119
_cell_measurement_theta_min      2.206
_cell_volume                     5222.1(7)
_computing_cell_refinement       'SAINT V8.40A (?, 2016)'
_computing_data_reduction        'SAINT V8.40A (?, 2016)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      150.0
_diffrn_measured_fraction_theta_full 0.991
_diffrn_measured_fraction_theta_max 0.987
_diffrn_measurement_device_type  'Bruker D8 VENTURE'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0694
_diffrn_reflns_av_unetI/netI     0.0645
_diffrn_reflns_Laue_measured_fraction_full 0.991
_diffrn_reflns_Laue_measured_fraction_max 0.987
_diffrn_reflns_limit_h_max       43
_diffrn_reflns_limit_h_min       -46
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            19359
_diffrn_reflns_point_group_measured_fraction_full 0.991
_diffrn_reflns_point_group_measured_fraction_max 0.987
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.411
_diffrn_reflns_theta_min         2.206
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    1.363
_exptl_absorpt_correction_T_max  0.9281
_exptl_absorpt_correction_T_min  0.7351
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0707 before and 0.0543 after correction. The Ratio of minimum to maximum transmission is 0.7920. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.518
_exptl_crystal_description       block
_exptl_crystal_F_000             2408
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.08
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.680
_refine_diff_density_min         -1.080
_refine_diff_density_rms         0.124
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.086
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     328
_refine_ls_number_reflns         5302
_refine_ls_number_restraints     334
_refine_ls_restrained_S_all      1.057
_refine_ls_R_factor_all          0.0782
_refine_ls_R_factor_gt           0.0526
_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^)+(0.0411P)^2^+33.6774P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1133
_refine_ls_wR_factor_ref         0.1267
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4089
_reflns_number_total             5302
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md00759c2.cif
_cod_data_source_block           1212s36_0m
_cod_database_code               7251053
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.935
_shelx_estimated_absorpt_t_min   0.822
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Rigid bond restraints
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
3. Uiso/Uaniso restraints and constraints
All non-hydrogen atoms have similar U: within 2A with sigma of 0.04 and sigma
for terminal atoms of 0.08
Uanis(C26) \\sim Ueq, Uanis(Cl1) \\sim Ueq, Uanis(C27) \\sim Ueq, Uanis(Cl2)
\\sim Ueq: with sigma of 0.005 and sigma for terminal atoms of 0.01
Uanis(Cl1) \\sim Ueq, Uanis(Cl2) \\sim Ueq: with sigma of 0.005 and sigma for
terminal atoms of 0.01
4. Others
 Fixed Sof: Cl1(0.5) Cl2(0.5) C26(0.5) H26A(0.5) H26B(0.5) C27(0.5) H27A(0.5)
 H27B(0.5)
5.a Riding coordinates:
 N2(H2)
5.b Secondary CH2 refined with riding coordinates:
 C16(H16A,H16B), C15(H15A,H15B), C7(H7A,H7B), C26(H26A,H26B), C27(H27A,H27B)
5.c Aromatic/amide H refined with riding coordinates:
 C13(H13), C21(H21), C12(H12), C24(H24), C9(H9), C23(H23), C2(H2A), C3(H3),
 C4(H4), C6(H6), C5(H5)
5.d Idealised Me refined as rotating group:
 C17(H17A,H17B,H17C), C19(H19A,H19B,H19C), C18(H18A,H18B,H18C)
;
_olex2_submission_special_instructions 'No special instructions were received'