Synthesis and evaluation of isothiazolo[4,5-b]pyridines as cyclin G-associated kinase (GAK) inhibitors
Ivanova, Yulia; Spittaels, Sander; Gao, Ling-Jie; Schols, Dominique; Van Meervelt, Luc; Froeyen, Mathy; Dehaen, Wim; De Jonghe, Steven; Organic & Biomolecular Chemistry 22 (2024) 7373–7389; doi:10.1039/D4OB00908H

data_7160104
_publ_section_title
;
 Synthesis and evaluation of isothiazolo[4,5-b]pyridines as cyclin
 G-associated kinase (GAK) inhibitors
;
_journal_issue                   36
_journal_name_full               'Organic &amp; Biomolecular Chemistry'
_journal_page_first              7373
_journal_page_last               7389
_journal_paper_doi               10.1039/D4OB00908H
_journal_volume                  22
_journal_year                    2024
_chemical_formula_moiety         'C6 H2 Br2 N2 S'
_chemical_formula_sum            'C6 H2 Br2 N2 S'
_chemical_formula_weight         293.98
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2023-01-26
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6408)
;
_audit_update_record
;
2024-05-23 deposited with the CCDC.	2024-07-22 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 93.419(7)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   4.0454(3)
_cell_length_b                   10.5096(8)
_cell_length_c                   19.0866(16)
_cell_measurement_reflns_used    2860
_cell_measurement_temperature    294(2)
_cell_measurement_theta_max      25.5300
_cell_measurement_theta_min      2.8720
_cell_volume                     810.03(11)
_computing_cell_refinement       'CrysAlisPro 1.171.42.73a (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.73a (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.73a (Rigaku OD, 2022)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2016/4 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      294(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 15.9631
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w     37.00  96.00   1.00    5.00    --   19.03-178.00-120.00   59
  2  \w    -25.00  92.00   1.00    5.00    --   19.03  19.00 -30.00  117
  3  \w    -11.00  42.00   1.00    5.00    --   19.03  77.00  90.00   53
  4  \w    -42.00  13.00   1.00    5.00    --  -16.92 -77.00 150.00   55
  5  \w     39.00  95.00   1.00    5.00    --   19.03 178.00 150.00   56
  6  \w     -6.00  91.00   1.00    5.00    --   19.03  38.00  60.00   97
  7  \w    -15.00  10.00   1.00    5.00    --   19.03 -99.00-120.00   25
  8  \w    -53.00  45.00   1.00    5.00    --   19.03 -38.00 -90.00   98
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Single source at offset/far, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0521298000
_diffrn_orient_matrix_UB_12      0.0458768000
_diffrn_orient_matrix_UB_13      -0.0242919000
_diffrn_orient_matrix_UB_21      -0.0373392000
_diffrn_orient_matrix_UB_22      -0.0430838000
_diffrn_orient_matrix_UB_23      -0.0279593000
_diffrn_orient_matrix_UB_31      -0.1634671000
_diffrn_orient_matrix_UB_32      0.0244374000
_diffrn_orient_matrix_UB_33      -0.0037579000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0322
_diffrn_reflns_av_unetI/netI     0.0260
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -5
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            8601
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.368
_diffrn_reflns_theta_min         2.886
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    10.193
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.42346
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.73a (Rigaku Oxford Diffraction, 2022)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    2.411
_exptl_crystal_description       plate
_exptl_crystal_F_000             552
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.25
_exptl_crystal_size_min          0.15
_refine_diff_density_max         0.516
_refine_diff_density_min         -0.475
_refine_diff_density_rms         0.079
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.082
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     100
_refine_ls_number_reflns         1638
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.082
_refine_ls_R_factor_all          0.0499
_refine_ls_R_factor_gt           0.0316
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0201P)^2^+0.6154P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0582
_refine_ls_wR_factor_ref         0.0645
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1262
_reflns_number_total             1638
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ob00908h2.cif
_cod_data_source_block           wdh1122_auto
_cod_depositor_comments          'Adding full bibliography for 7160104.cif.'
_cod_database_code               7160104
_shelx_shelxl_version_number     2016/4
_chemical_oxdiff_formula         C12H4N4S2Br2
_shelx_estimated_absorpt_t_max   0.310
_shelx_estimated_absorpt_t_min   0.150
_reflns_odcompleteness_completeness 99.77
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups
2.a Aromatic/amide H refined with riding coordinates:
 C6(H6), C8(H8)
;
_shelx_res_checksum              5820
_olex2_submission_original_sample_id 'Yulia Ivanova'
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 2.121
_oxdiff_exptl_absorpt_empirical_full_min 0.674