Diversifying the Triquinazine Scaffold of a Janus Kinase Inhibitor
Mulliri, Kleni; Meier, Kris; Feuchter, Johanna-Dorothea; Javor, Sacha; Andrade Meirelles, Matheus; Reymond, Jean-Louis; RSC Medicinal Chemistry  (2025) –; doi:10.1039/D5MD00921A

data_7251305
_publ_section_title
;
 Diversifying the Triquinazine Scaffold of a Janus Kinase Inhibitor
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D5MD00921A
_journal_year                    2025
_chemical_formula_moiety         'C19 H25 N O5'
_chemical_formula_sum            'C19 H25 N O5'
_chemical_formula_weight         347.4
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_cell_setting           triclinic
_symmetry_Int_Tables_number      2
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_atom_sites_solution_hydrogens   difmap
_atom_sites_solution_primary     dual
_audit_creation_date             2021-12-06T15:20:37-00:00
_audit_update_record
;
2025-08-22 deposited with the CCDC.	2025-11-13 downloaded from the CCDC.
;
_cell_angle_alpha                65.3764(11)
_cell_angle_beta                 76.8583(11)
_cell_angle_gamma                86.5176(10)
_cell_formula_units_Z            4
_cell_length_a                   12.32883(17)
_cell_length_b                   12.61335(13)
_cell_length_c                   13.40303(17)
_cell_measurement_reflns_used    54597
_cell_measurement_temperature    173.01(10)
_cell_measurement_theta_max      79.769
_cell_measurement_theta_min      3.678
_cell_volume                     1843.76(4)
_computing_cell_refinement       'CrysAlisPro 1.171.41.112a (Rigaku OD, 2021)'
_computing_data_collection       'CrysAlisPro 1.171.41.112a (Rigaku OD, 2021)'
_computing_data_reduction        'CrysAlisPro 1.171.41.112a (Rigaku OD, 2021)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      173.01(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.997
_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    -95.00  -3.00   0.50    0.60    --  -23.00 -69.00-159.00  184
  2  \w    -42.00  50.00   0.50    0.60    --  -23.00  69.00 -26.00  184
  3  \w     29.00 120.00   0.50    0.60    --   47.95  69.00 -26.00  182
  4  \w     94.00 177.00   0.50    2.00    --  113.25  69.00 -26.00  166
  5  \w     42.00  81.00   0.50    2.00    --  113.25 -69.00-159.00   78
  6  \w    -70.00 -12.00   0.50    0.60    --  -23.00 125.00-120.00  116
  7  \w    -95.00 -10.00   0.50    0.60    --  -23.00 -45.00 -30.00  170
  8  \w     -2.00  28.00   0.50    0.60    --   30.00  97.00 -42.74   60
  9  \w      5.00  42.00   0.50    0.60    --   34.00  91.00 100.11   74
 10  \w      8.00  41.00   0.50    0.60    --   38.00  92.00   9.16   66
 11  \w     13.00  42.00   0.50    0.60    --   42.00  91.00 118.45   58
 12  \w     17.00  43.00   0.50    0.60    --   46.00  90.00-107.70   52
 13  \w    -24.00  67.00   0.50    0.60    --   47.95 -69.00-159.00  182
 14  \w     -1.00  81.00   0.50    0.60    --   47.95 -99.00 150.00  164
 15  \w     28.00 122.00   0.50    0.60    --   50.00  76.00-136.87  188
 16  \w     28.00 122.00   0.50    0.60    --   50.00  75.00   5.11  188
 17  \w     31.00 126.00   0.50    0.60    --   54.00  77.00  22.64  190
 18  \w     36.00 131.00   0.50    0.60    --   58.00  76.00 -68.47  190
 19  \w     35.00 131.00   0.50    0.60    --   58.00  77.00  69.23  192
 20  \w     36.00 131.00   0.50    0.60    --   58.00  75.00 170.64  190
 21  \w     36.00 131.00   0.50    0.60    --   58.00  76.00 -98.83  190
 22  \w     40.00 135.00   0.50    0.60    --   62.00  76.00 -53.83  190
 23  \w     46.00 139.00   0.50    0.60    --   66.00  71.00  31.66  186
 24  \w     44.00 139.00   0.50    0.60    --   66.00  75.00  46.26  190
 25  \w     43.00 139.00   0.50    0.60    --   66.00  77.00 171.30  192
 26  \w     44.00 139.00   0.50    0.60    --   66.00  76.00-166.50  190
 27  \w     44.00 139.00   0.50    0.60    --   66.00  75.00 102.10  190
 28  \w     48.00 143.00   0.50    0.60    --   70.00  76.00 -49.29  190
 29  \w     51.00 143.00   0.50    0.60    --   70.00  67.00 144.09  184
 30  \w     47.00 143.00   0.50    0.60    --   70.00  77.00-143.32  192
 31  \w     48.00 143.00   0.50    0.60    --   70.00  75.00-121.85  190
 32  \w     48.00 143.00   0.50    0.60    --   70.00  75.00 -20.40  190
 33  \w     52.00 146.00   0.50    0.60    --   74.00  76.00  70.84  188
 34  \w     59.00 151.00   0.50    0.60    --   78.00  69.00-175.14  184
 35  \w     56.00 151.00   0.50    0.60    --   78.00  76.00-115.72  190
 36  \w     55.00 151.00   0.50    0.60    --   78.00  77.00 -18.23  192
 37  \w     57.00 151.00   0.50    0.60    --   78.00  74.00 148.38  188
 38  \w     64.00 151.00   0.50    0.60    --   78.00  54.00  44.10  174
 39  \w     61.00  97.00   0.50    2.00    --   82.00  72.00-107.16   72
 40  \w    116.00 158.00   0.50    2.00    --   86.00  57.00-162.10   84
 41  \w     72.00 108.00   0.50    2.00    --   86.00  57.00-162.10   72
 42  \w     73.00  99.00   0.50    2.00    --   90.00  64.00  51.73   52
 43  \w    137.00 162.00   0.50    2.00    --   90.00  72.00 -53.82   50
 44  \w     75.00 102.00   0.50    2.00    --   90.00  65.00  91.21   54
 45  \w     69.00 116.00   0.50    2.00    --   90.00  72.00 -53.82   94
 46  \w     72.00 108.00   0.50    2.00    --   94.00  76.00  55.04   72
 47  \w    137.00 163.00   0.50    2.00    --   94.00  59.00 136.14   52
 48  \w    141.00 167.00   0.50    2.00    --   94.00  76.00  55.04   52
 49  \w     80.00 106.00   0.50    2.00    --   94.00  59.00 136.14   52
 50  \w    140.00 175.00   0.50    2.00    --  106.00  62.00-112.17   70
 51  \w     89.00 127.00   0.50    2.00    --  106.00  62.00-112.17   76
 52  \w    142.00 176.00   0.50    2.00    --  113.25  77.00-120.00   68
 53  \w     92.00 129.00   0.50    2.00    --  113.25  77.00-120.00   74
 54  \w     49.00 104.00   0.50    2.00    --  113.25 -94.00  60.00  110
 55  \w     76.00 104.00   0.50    2.00    --  113.25 -94.00 120.00   56
 56  \w     98.00 169.00   0.50    2.00    --  113.25  61.00 -30.00  142
 57  \w     44.00  71.00   0.50    2.00    --  113.25 -94.00 120.00   54
 58  \w     92.00 158.00   0.50    2.00    --  113.25  77.00  60.00  132
 59  \w     81.00 106.00   0.50    2.00    --  113.25 -94.00-150.00   50
 60  \w     54.00 105.00   0.50    2.00    --  113.25 -94.00 -90.00  102
 61  \w    105.00 131.00   0.50    2.00    --  113.25  61.00 -60.00   52
 62  \w     50.00  77.00   0.50    2.00    --  113.25 -94.00-150.00   54
 63  \w     76.00 104.00   0.50    2.00    --  113.25 -94.00   0.00   56
 64  \w     42.00 102.00   0.50    2.00    --  113.25 -94.00 -60.00  120
 65  \w     42.00  72.00   0.50    2.00    --  113.25 -94.00   0.00   60
 66  \w    141.00 172.00   0.50    2.00    --  113.25  61.00 -90.00   62
 67  \w    152.00 177.00   0.50    2.00    --  113.25  61.00  90.00   50
 68  \w     98.00 125.00   0.50    2.00    --  113.25  61.00  90.00   54
 69  \w     98.00 125.00   0.50    2.00    --  113.25  61.00 -90.00   54
 70  \w    127.00 170.00   0.50    2.00    --  113.25  70.00 177.55   86
 71  \w     48.00 101.00   0.50    2.00    --  113.25 -77.00   0.00  106
 72  \w     99.00 151.00   0.50    2.00    --  113.25  61.00 120.00  104
 73  \w     94.00 120.00   0.50    2.00    --  113.25  70.00 177.55   52
 74  \w     75.00 106.00   0.50    2.00    --  113.25 -94.00 150.00   62
 75  \w     45.00  72.00   0.50    2.00    --  113.25 -94.00 150.00   54
 76  \w     98.00 149.00   0.50    2.00    --  113.25  61.00-150.00  102
 77  \w     74.00 104.00   0.50    2.00    --  113.25 -94.00  90.00   60
 78  \w     44.00  75.00   0.50    2.00    --  113.25 -77.00  60.00   62
 79  \w     79.00 106.00   0.50    2.00    --  113.25 -97.00  -7.71   54
 80  \w    141.00 177.00   0.50    2.00    --  113.25  77.00 120.00   72
 81  \w    140.00 172.00   0.50    2.00    --  113.25  77.00-150.00   64
 82  \w     93.00 126.00   0.50    2.00    --  113.25  77.00 120.00   66
 83  \w     91.00 123.00   0.50    2.00    --  113.25  77.00-150.00   64
 84  \w     44.00  76.00   0.50    2.00    --  113.25 -97.00  -7.71   64
 85  \w     93.00 147.00   0.50    2.00    --  113.25  77.00  30.00  108
 86  \w    117.00 177.00   0.50    2.00    --  113.25  90.00  63.51  120
 87  \w    135.00 177.00   0.50    2.00    --  113.25  77.00-180.00   84
 88  \w     93.00 123.00   0.50    2.00    --  113.25  77.00-180.00   60
 89  \w    129.00 177.00   0.50    2.00    --  113.25  77.00 150.00   96
 90  \w    100.00 176.00   0.50    2.00    --  113.25  61.00  30.00  152
 91  \w     94.00 163.00   0.50    2.00    --  113.25  68.00  -6.36  138
 92  \w     97.00 160.00   0.50    2.00    --  113.25  61.00 150.00  126
 93  \w     91.00 120.00   0.50    2.00    --  113.25  77.00 150.00   58
 94  \w     78.00 104.00   0.50    2.00    --  113.25 -94.00-180.00   52
 95  \w    131.00 177.00   0.50    2.00    --  113.25  30.00-120.00   92
 96  \w     44.00  84.00   0.50    2.00    --  113.25 -77.00-120.00   80
 97  \w     42.00  74.00   0.50    2.00    --  113.25 -94.00-180.00   64
 98  \w    148.00 176.00   0.50    2.00    --  113.25  73.00 -82.00   56
 99  \w    134.00 175.00   0.50    2.00    --  113.25  77.00 -60.00   82
100  \w     93.00 124.00   0.50    2.00    --  113.25  77.00 -60.00   62
101  \w    125.00 176.00   0.50    2.00    --  113.25  77.00  90.00  102
102  \w    151.00 176.00   0.50    2.00    --  113.25  77.00   0.00   50
103  \w     91.00 121.00   0.50    2.00    --  113.25  77.00   0.00   60
104  \w     91.00 117.00   0.50    2.00    --  113.25  77.00  90.00   52
105  \w     92.00 126.00   0.50    2.00    --  113.25  73.00 -82.00   68
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0050367
_diffrn_orient_matrix_UB_12      -0.124618
_diffrn_orient_matrix_UB_13      0.090098
_diffrn_orient_matrix_UB_21      0.100838
_diffrn_orient_matrix_UB_22      -0.022686
_diffrn_orient_matrix_UB_23      -0.0795826
_diffrn_orient_matrix_UB_31      0.0793459
_diffrn_orient_matrix_UB_32      0.0450958
_diffrn_orient_matrix_UB_33      0.0486811
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0262
_diffrn_reflns_av_unetI/netI     0.0343
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            72714
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.997
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.993
_diffrn_reflns_theta_min         3.684
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.741
_exptl_absorpt_correction_T_max  1
_exptl_absorpt_correction_T_min  0.58861
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
        CrysAlisPro 1.171.41.112a (Rigaku Oxford Diffraction, 2021)
        Empirical absorption correction using spherical harmonics,
        implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.252
_exptl_crystal_description       block
_exptl_crystal_F_000             744
_exptl_crystal_size_max          0.207
_exptl_crystal_size_mid          0.093
_exptl_crystal_size_min          0.084
_refine_diff_density_max         0.256
_refine_diff_density_min         -0.177
_refine_diff_density_rms         0.03
_refine_ls_extinction_coef       0.00096(14)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.03
_refine_ls_hydrogen_treatment    refall
_refine_ls_matrix_type           full
_refine_ls_number_parameters     652
_refine_ls_number_reflns         7471
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.03
_refine_ls_R_factor_all          0.0349
_refine_ls_R_factor_gt           0.033
_refine_ls_shift/su_max          0
_refine_ls_shift/su_mean         0
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0434P)^2^+0.3909P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.086
_refine_ls_wR_factor_ref         0.0876
_reflns_Friedel_coverage         0
_reflns_number_gt                6984
_reflns_number_total             7471
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md00921a2.cif
_cod_data_source_block           21JLR017_MK-065(22-55)
_cod_database_code               7251305
_shelx_estimated_absorpt_t_min   0.862
_shelx_estimated_absorpt_t_max   0.94
_oxdiff_exptl_absorpt_empirical_details
;
        Empirical correction (ABSPACK) includes:
        - Absorption correction using spherical harmonics
        - Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.649
_oxdiff_exptl_absorpt_empirical_full_min 0.757
_shelx_shelxl_version_number     2018/3
_olex2_refinement_description
;
;
_shelx_res_checksum              40774
_shelx_hkl_checksum              32046