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_7251303
_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         'C23 H27 N5'
_chemical_formula_sum            'C23 H27 N5'
_chemical_formula_weight         373.49
_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   geom
_atom_sites_solution_primary     dual
_audit_update_record
;
2025-08-22 deposited with the CCDC.	2025-11-13 downloaded from the CCDC.
;
_cell_angle_alpha                88.6463(13)
_cell_angle_beta                 79.6474(14)
_cell_angle_gamma                84.9350(14)
_cell_formula_units_Z            2
_cell_length_a                   7.89197(15)
_cell_length_b                   8.29233(13)
_cell_length_c                   15.5755(2)
_cell_measurement_reflns_used    17517
_cell_measurement_temperature    173.01(10)
_cell_measurement_theta_max      79.137
_cell_measurement_theta_min      2.874
_cell_volume                     998.76(3)
_computing_cell_refinement       'CrysAlisPro 1.171.41.99a (Rigaku OD, 2021)'
_computing_data_collection       'CrysAlisPro 1.171.41.99a (Rigaku OD, 2021)'
_computing_data_reduction        'CrysAlisPro 1.171.41.99a (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    -82.00 -25.00   0.50    0.35    --  -21.00 149.00-111.00  114
  2  \w    -67.00 -11.00   0.50    0.35    --  -21.00 123.00  84.00  112
  3  \w     33.00  94.00   0.50    0.35    --   47.66-123.00   4.00  122
  4  \w     42.00 110.00   0.50    1.90    --  113.25-123.00   4.00  136
  5  \w     96.00 177.00   0.50    1.90    --  113.25 123.00  84.00  162
  6  \w    -34.00  51.00   0.50    0.35    --  -21.00  45.00-180.00  170
  7  \w    -93.00  -6.00   0.50    0.35    --  -21.00 -57.00-120.00  174
  8  \w     -3.00  34.00   0.50    0.35    --   28.00  94.00-179.58   74
  9  \w     -1.00  27.00   0.50    0.35    --   32.00  98.00  -8.20   56
 10  \w     16.00  43.00   0.50    0.35    --   44.00  88.00-178.87   54
 11  \w    -24.00  70.00   0.50    0.35    --   47.66 -77.00-180.00  188
 12  \w    -27.00  23.00   0.50    0.35    --   47.66 -19.00  90.00  100
 13  \w     25.00 120.00   0.50    0.35    --   47.66  77.00 120.00  190
 14  \w     34.00  95.00   0.50    0.35    --   47.66-125.00 150.00  122
 15  \w     27.00 121.00   0.50    0.35    --   48.00  74.00 -29.08  188
 16  \w     30.00 125.00   0.50    0.35    --   52.00  75.00 -84.71  190
 17  \w     29.00 125.00   0.50    0.35    --   52.00  77.00  67.83  192
 18  \w     29.00 125.00   0.50    0.35    --   52.00  77.00-139.71  192
 19  \w     34.00 129.00   0.50    0.35    --   56.00  75.00   9.30  190
 20  \w     39.00 132.00   0.50    0.35    --   60.00  74.00  58.82  186
 21  \w     38.00 132.00   0.50    0.35    --   60.00  76.00 -28.14  188
 22  \w     39.00 132.00   0.50    0.35    --   60.00  73.00 151.80  186
 23  \w     42.00 137.00   0.50    0.35    --   64.00  76.00 161.87  190
 24  \w     45.00 137.00   0.50    0.35    --   64.00  68.00-115.84  184
 25  \w     41.00 137.00   0.50    0.35    --   64.00  77.00  14.18  192
 26  \w     42.00 137.00   0.50    0.35    --   64.00  75.00 -84.30  190
 27  \w     45.00 140.00   0.50    0.35    --   68.00  77.00 105.41  190
 28  \w     48.00 140.00   0.50    0.35    --   68.00  71.00-179.80  184
 29  \w     47.00 140.00   0.50    0.35    --   68.00  74.00  88.81  186
 30  \w     46.00 140.00   0.50    0.35    --   68.00  75.00-167.60  188
 31  \w     47.00 140.00   0.50    0.35    --   68.00  73.00  28.07  186
 32  \w     46.00 140.00   0.50    0.35    --   68.00  76.00 -97.93  188
 33  \w     62.00 134.00   0.50    0.35    --   76.00  58.00 155.15  144
 34  \w    139.00 173.00   0.50    1.90    --  113.25  77.00-180.00   68
 35  \w     92.00 119.00   0.50    1.90    --  113.25  77.00-180.00   54
 36  \w     67.00 106.00   0.50    1.90    --  113.25 -94.00 150.00   78
 37  \w     98.00 148.00   0.50    1.90    --  113.25  61.00 -90.00  100
 38  \w    130.00 177.00   0.50    1.90    --  113.25  77.00 150.00   94
 39  \w     42.00  67.00   0.50    1.90    --  113.25 -61.00  60.00   50
 40  \w     99.00 150.00   0.50    1.90    --  113.25  61.00-150.00  102
 41  \w     91.00 118.00   0.50    1.90    --  113.25  77.00 120.00   54
 42  \w     93.00 120.00   0.50    1.90    --  113.25  77.00 150.00   54
 43  \w     79.00 107.00   0.50    1.90    --  113.25-125.00-180.00   56
 44  \w     92.00 117.00   0.50    1.90    --  113.25  77.00-150.00   50
 45  \w     42.00  78.00   0.50    1.90    --  113.25-125.00-180.00   72
 46  \w    142.00 174.00   0.50    1.90    --  113.25  61.00-120.00   64
 47  \w     81.00 106.00   0.50    1.90    --  113.25 -94.00-180.00   50
 48  \w    135.00 172.00   0.50    1.90    --  113.25  77.00-150.00   74
 49  \w     91.00 124.00   0.50    1.90    --  113.25  77.00   0.00   66
 50  \w    134.00 170.00   0.50    1.90    --  113.25  77.00   0.00   72
 51  \w     97.00 158.00   0.50    1.90    --  113.25  61.00 -60.00  122
 52  \w    122.00 177.00   0.50    1.90    --  113.25  77.00 120.00  110
 53  \w     91.00 136.00   0.50    1.90    --  113.25  77.00 -60.00   90
 54  \w    146.00 174.00   0.50    1.90    --  113.25  77.00 -60.00   56
 55  \w     93.00 151.00   0.50    1.90    --  113.25  77.00 -90.00  116
 56  \w     97.00 161.00   0.50    1.90    --  113.25  61.00 -30.00  128
 57  \w     91.00 136.00   0.50    1.90    --  113.25  77.00  60.00   90
 58  \w    115.00 169.00   0.50    1.90    --  113.25  45.00 120.00  108
 59  \w     63.00 106.00   0.50    1.90    --  113.25 -94.00-120.00   86
 60  \w     98.00 136.00   0.50    1.90    --  113.25  61.00-120.00   76
 61  \w    152.00 177.00   0.50    1.90    --  113.25  61.00  90.00   50
 62  \w     91.00 138.00   0.50    1.90    --  113.25  77.00-120.00   94
 63  \w     97.00 133.00   0.50    1.90    --  113.25  61.00  90.00   72
 64  \w     71.00 104.00   0.50    1.90    --  113.25 -94.00  30.00   66
 65  \w    130.00 175.00   0.50    1.90    --  113.25  77.00 -30.00   90
 66  \w     42.00  67.00   0.50    1.90    --  113.25 -61.00 120.00   50
 67  \w     91.00 122.00   0.50    1.90    --  113.25  77.00 -30.00   62
 68  \w     42.00  68.00   0.50    1.90    --  113.25 -61.00  90.00   52
 69  \w     42.00  75.00   0.50    1.90    --  113.25 -94.00-180.00   66
 70  \w     45.00  99.00   0.50    1.90    --  113.25 -77.00-180.00  108
 71  \w     45.00  99.00   0.50    1.90    --  113.25 -77.00  60.00  108
 72  \w     98.00 170.00   0.50    1.90    --  113.25  61.00  60.00  144
 73  \w     84.00 111.00   0.50    1.90    --  113.25-125.00  30.00   54
 74  \w     50.00  77.00   0.50    1.90    --  113.25-125.00  30.00   54
 75  \w    132.00 159.00   0.50    1.90    --  113.25  61.00   0.00   54
 76  \w     42.00  67.00   0.50    1.90    --  113.25 -61.00 -60.00   50
 77  \w     43.00  81.00   0.50    1.90    --  113.25-125.00 -30.00   76
 78  \w     97.00 127.00   0.50    1.90    --  113.25  61.00 150.00   60
 79  \w    147.00 174.00   0.50    1.90    --  113.25  61.00  30.00   54
 80  \w    101.00 154.00   0.50    1.90    --  113.25 125.00   0.00  106
 81  \w     44.00  97.00   0.50    1.90    --  113.25 -77.00  30.00  106
 82  \w     91.00 133.00   0.50    1.90    --  113.25  77.00  90.00   84
 83  \w     91.00 124.00   0.50    1.90    --  113.25  77.00  30.00   66
 84  \w     97.00 125.00   0.50    1.90    --  113.25  61.00  30.00   56
 85  \w     74.00 101.00   0.50    1.90    --  113.25 -77.00-120.00   54
 86  \w     47.00  74.00   0.50    1.90    --  113.25 -77.00   0.00   54
 87  \w     42.00  67.00   0.50    1.90    --  113.25 -61.00-120.00   50
 88  \w    100.00 127.00   0.50    1.90    --  113.25  61.00   0.00   54
 89  \w    100.00 157.00   0.50    1.90    --  113.25  61.00-180.00  114
;
_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      -0.0676827
_diffrn_orient_matrix_UB_12      0.1276849
_diffrn_orient_matrix_UB_13      0.0710268
_diffrn_orient_matrix_UB_21      0.0410416
_diffrn_orient_matrix_UB_22      -0.1231655
_diffrn_orient_matrix_UB_23      0.0705884
_diffrn_orient_matrix_UB_31      0.1827606
_diffrn_orient_matrix_UB_32      0.0575756
_diffrn_orient_matrix_UB_33      -0.0090923
_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  0.0443
_diffrn_reflns_av_unetI/netI     0.0498
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            29835
_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         70.855
_diffrn_reflns_theta_min         2.884
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.591
_exptl_absorpt_correction_T_max  1
_exptl_absorpt_correction_T_min  0.77768
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
        CrysAlisPro 1.171.41.99a (Rigaku Oxford Diffraction, 2021)
        Empirical absorption correction using spherical harmonics,
        implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.242
_exptl_crystal_description       block
_exptl_crystal_F_000             400
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.166
_exptl_crystal_size_min          0.133
_refine_diff_density_max         0.453
_refine_diff_density_min         -0.235
_refine_diff_density_rms         0.049
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.033
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     253
_refine_ls_number_reflns         3846
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.033
_refine_ls_R_factor_all          0.0644
_refine_ls_R_factor_gt           0.0604
_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^)+(0.0977P)^2^+0.5048P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1707
_refine_ls_wR_factor_ref         0.1744
_reflns_Friedel_coverage         0
_reflns_number_gt                3460
_reflns_number_total             3846
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md00921a2.cif
_cod_data_source_block           21JLR003_KM-045-F1
_cod_database_code               7251303
_shelx_estimated_absorpt_t_min   0.891
_shelx_estimated_absorpt_t_max   0.926
_oxdiff_exptl_absorpt_empirical_details
;
        Empirical correction (ABSPACK) includes:
        - Absorption correction using spherical harmonics
        - Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 2.105
_oxdiff_exptl_absorpt_empirical_full_min 0.616
_shelx_shelxl_version_number     2018/3
_olex2_refinement_description
;
        1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
        2.a Ternary CH refined with riding coordinates:
 C11(H11), C14(H14)
        2.b Secondary CH2 refined with riding coordinates:
 C17(H17A,H17B), C12(H12A,H12B), C9(H9A,H9B), C7(H7A,H7B), C8(H8A,H8B),
 C16(H16A,H16B), C13(H13A,H13B), C15(H15A,H15B)
        2.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C1(H1A), C2(H2), C5(H5), C23(H23), C19(H19), C22(H22), C20(H20),
 C21(H21)
;
_shelx_res_checksum              67448
_shelx_hkl_checksum              81125