Discovery of a Candidate Containing an (S)-3,3-Difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-inden Scaffold as a Highly Potent Pan-Inhibitor of the BCR-ABL Kinase Including the T315I-Resistant Mutant for the Treatment of Chronic Myeloid Leukemia
Zhang, Dongfeng; Li, Peng; Gao, Yongxin; Song, Yaoyao; Zhu, Yaqin; Su, Hong; Yang, Beibei; Li, Li; Li, Gang; Gong, Ningbo; Lu, Yang; Shao, Huanjie; Yu, Chunrong; Huang, Haihong; Journal of Medicinal Chemistry  (2021) –; doi:10.1021/acs.jmedchem.1c00082

data_1562742
_publ_section_title
;
 Discovery of a Candidate Containing an
 (S)-3,3-Difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-inden Scaffold
 as a Highly Potent Pan-Inhibitor of the BCR-ABL Kinase Including the
 T315I-Resistant Mutant for the Treatment of Chronic Myeloid Leukemia
;
_journal_name_full               'Journal of Medicinal Chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.1c00082
_journal_year                    2021
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C68 H100 F4 N6 O21 S4'
_chemical_formula_sum            'C68 H100 F4 N6 O21 S4'
_chemical_formula_weight         1541.78
_space_group_IT_number           5
_space_group_name_Hall           'C 2y'
_space_group_name_H-M_alt        'C 1 2 1'
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  'C 2y'
_symmetry_space_group_name_H-M   'C 1 2 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 132.313(5)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   32.412(12)
_cell_length_b                   6.476(3)
_cell_length_c                   23.549(8)
_cell_measurement_reflns_used    1782
_cell_measurement_temperature    295(2)
_cell_measurement_theta_max      72.0
_cell_measurement_theta_min      27.4
_cell_volume                     3655(3)
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      295(2)
_diffrn_measured_fraction_theta_full 0.975
_diffrn_measured_fraction_theta_max 0.975
_diffrn_measurement_device_type  'MicroMax 002+'
_diffrn_measurement_method       /w/k
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0720
_diffrn_reflns_av_sigmaI/netI    0.0643
_diffrn_reflns_limit_h_max       39
_diffrn_reflns_limit_h_min       -39
_diffrn_reflns_limit_k_max       3
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       29
_diffrn_reflns_limit_l_min       -28
_diffrn_reflns_number            14137
_diffrn_reflns_theta_full        72.26
_diffrn_reflns_theta_max         72.26
_diffrn_reflns_theta_min         2.54
_diffrn_standards_decay_%        0
_diffrn_standards_interval_count 0
_diffrn_standards_interval_time  0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    1.941
_exptl_absorpt_correction_T_max  0.733
_exptl_absorpt_correction_T_min  0.454
_exptl_absorpt_correction_type   multi-scan
_exptl_crystal_colour            Colorless
_exptl_crystal_density_diffrn    1.401
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       Prism
_exptl_crystal_F_000             1636
_exptl_crystal_size_max          0.61
_exptl_crystal_size_mid          0.36
_exptl_crystal_size_min          0.16
_refine_diff_density_max         0.406
_refine_diff_density_min         -0.544
_refine_diff_density_rms         0.084
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.02(2)
_refine_ls_extinction_coef       0.00149(15)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     SHELXL
_refine_ls_goodness_of_fit_ref   1.015
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     478
_refine_ls_number_reflns         4872
_refine_ls_number_restraints     5
_refine_ls_restrained_S_all      1.015
_refine_ls_R_factor_all          0.0624
_refine_ls_R_factor_gt           0.0562
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0874P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1368
_refine_ls_wR_factor_ref         0.1426
_reflns_number_gt                3904
_reflns_number_total             4872
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jm1c00082_si_003.cif
_cod_data_source_block           5715
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_exptl_absorpt_correction_type' value 'Multi-scan' was
changed to 'multi-scan' in accordance with the
/home/data/users/saulius/crontab/automatic-downloads/rss-feeds/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26.

Automatic conversion script
Id: cif_fix_values 7556 2019-12-06 15:28:31Z antanas 
;
_cod_original_cell_volume        3655(2)
_cod_original_sg_symbol_H-M      C2
_cod_database_code               1562742