Design, synthesis, and biological evaluation of X19: a matrine pyrazole derivatives therapeutic candidate
Xu, Tingguo; Dai, Suyi; Hu, Zhouxing; Ou, Anqi; Wang, Xingdong; Wang, Lisheng; RSC Medicinal Chemistry  (2026) –; doi:10.1039/D5MD01118C

data_7251764
_publ_section_title
;
 Design, synthesis, and biological evaluation of X19: a matrine pyrazole
 derivatives therapeutic candidate
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D5MD01118C
_journal_year                    2026
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C20 H26 N6'
_chemical_formula_sum            'C20 H26 N6'
_chemical_formula_weight         350.47
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2024-03-07
_audit_creation_method
;
Olex2 1.5-beta
(compiled 2022.04.07 svn.rca3783a0 for OlexSys, GUI svn.r6439)
;
_audit_update_record
;
2025-11-26 deposited with the CCDC.	2026-02-20 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90.0907(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.86561(10)
_cell_length_b                   14.71412(15)
_cell_length_c                   13.82658(18)
_cell_measurement_reflns_used    11903
_cell_measurement_temperature    150.00(10)
_cell_measurement_theta_max      73.7020
_cell_measurement_theta_min      2.9650
_cell_volume                     1803.67(4)
_computing_cell_refinement       'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 1.5-beta (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-beta (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      150.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.2684
_diffrn_detector_type            AtlasS2
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.987
_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   -129.00  47.00   1.00    1.00    --  -40.73   0.00  90.00  176
  2  \w     23.00  97.00   1.00    1.00    --   40.73-125.00  30.00   74
  3  \w     70.00 118.00   1.00    1.00    --   40.73 162.00 -41.00   48
  4  \w     75.00 178.00   1.00    1.00    --  107.58  77.00-180.00  103
  5  \w     94.00 178.00   1.00    1.00    --  107.58 125.00-150.00   84
  6  \w     25.00 109.00   1.00    1.00    --  107.58 -94.00 150.00   84
  7  \w     94.00 178.00   1.00    1.00    --  107.58 125.00  60.00   84
  8  \w     31.00 136.00   1.00    1.00    --  107.58 -30.00   0.00  105
  9  \w     94.00 178.00   1.00    1.00    --  107.58 125.00 -30.00   84
 10  \w     34.00 122.00   1.00    1.00    --  107.58-125.00 -60.00   88
 11  \w   -115.00 -70.00   1.00    1.00    --  -40.73 -38.00   0.00   45
 12  \w    -20.00  27.00   1.00    1.00    --  -40.98  77.00-120.00   47
 13  \w     32.00  64.00   1.00    1.00    --   40.98  38.00-120.00   32
 14  \w     24.00  51.00   1.00    1.00    --   40.98-125.00 120.00   27
 15  \w     84.00 144.00   1.00    1.00    --  107.58  45.00-120.00   60
 16  \w    117.00 176.00   1.00    1.00    --  107.58  77.00 150.00   59
 17  \w     75.00 100.00   1.00    1.00    --  107.58  77.00 150.00   25
 18  \w     80.00 105.00   1.00    1.00    --  107.58  61.00-150.00   25
 19  \w     27.00 102.00   1.00    1.00    --  107.58 -94.00   0.00   75
 20  \w     58.00 102.00   1.00    1.00    --  107.58 -94.00  60.00   44
 21  \w     81.00 112.00   1.00    1.00    --  107.58  61.00-180.00   31
 22  \w     83.00 109.00   1.00    1.00    --  107.58  45.00-150.00   26
 23  \w    103.00 129.00   1.00    1.00    --  107.58  45.00 150.00   26
 24  \w     86.00 147.00   1.00    1.00    --  107.58  77.00 120.00   61
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, AtlasS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0880563000
_diffrn_orient_matrix_UB_12      0.0680337000
_diffrn_orient_matrix_UB_13      -0.0630935000
_diffrn_orient_matrix_UB_21      0.0845319000
_diffrn_orient_matrix_UB_22      0.0342933000
_diffrn_orient_matrix_UB_23      0.0903236000
_diffrn_orient_matrix_UB_31      0.1236812000
_diffrn_orient_matrix_UB_32      -0.0718118000
_diffrn_orient_matrix_UB_33      -0.0165951000
_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  0.0382
_diffrn_reflns_av_unetI/netI     0.0340
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.987
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            16284
_diffrn_reflns_point_group_measured_fraction_full 0.993
_diffrn_reflns_point_group_measured_fraction_max 0.968
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.859
_diffrn_reflns_theta_min         3.196
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.633
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.87571
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.43f (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light yellow'
_exptl_crystal_density_diffrn    1.291
_exptl_crystal_description       block
_exptl_crystal_F_000             752
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.13
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.253
_refine_diff_density_min         -0.265
_refine_diff_density_rms         0.056
_refine_ls_abs_structure_details
;
 Flack x determined using 3087 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.09(14)
_refine_ls_extinction_coef       0.0058(5)
_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   1.082
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     470
_refine_ls_number_reflns         7081
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.082
_refine_ls_R_factor_all          0.0552
_refine_ls_R_factor_gt           0.0548
_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^)+(0.0588P)^2^+1.6888P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1472
_refine_ls_wR_factor_ref         0.1476
_reflns_Friedel_coverage         0.885
_reflns_Friedel_fraction_full    0.986
_reflns_Friedel_fraction_max     0.947
_reflns_number_gt                6997
_reflns_number_total             7081
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md01118c2.cif
_cod_data_source_block           n6
_cod_database_code               7251764
_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
2.a Ternary CH refined with riding coordinates:
 C1(H1), C5(H5), C6(H6), C10(H10), C29(H29), C30(H30), C32(H32), C36(H36)
2.b Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), C2(H2A,H2B), C3(H3A,H3B), C4(H4A,H4B), C40(H40A,H40B), C8(H8A,
 H8B), C9(H9A,H9B), C11(H11A,H11B), C12(H12A,H12B), C27(H27A,H27B), C28(H28A,
 H28B), C31(H31A,H31B), C33(H33A,H33B), C34(H34A,H34B), C35(H35A,H35B),
 C37(H37A,H37B), C38(H38A,H38B), C39(H39A,H39B)
2.c Aromatic/amide H refined with riding coordinates:
 C15(H15), C17(H17), C18(H18), C19(H19), C20(H20), C21(H21), C22(H22), C24(H24)
;
_shelx_res_checksum              27120
_olex2_date_sample_data_collection 2024-03-06
_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
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.706
_oxdiff_exptl_absorpt_empirical_full_min 0.615