A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats.
Ren, Shuyue; Jiao, Lingtai; Yang, Shiying; Zhang, Li; Song, Junke; Yu, Haoying; Wang, Jingrong; Lv, Tingting; Sun, Lan; Lu, Yang; Du, Guanhua; Pharmaceutics 12 (2020) 906–; doi:10.3390/pharmaceutics12100906

data_1559277
_publ_section_title
;
 A Novel Co-Crystal of Bexarotene and Ligustrazine Improves
 Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats.
;
_journal_issue                   10
_journal_name_full               Pharmaceutics
_journal_page_first              906
_journal_paper_doi               10.3390/pharmaceutics12100906
_journal_volume                  12
_journal_year                    2020
_chemical_formula_moiety         'C24 H28 O2, C4 H6 N'
_chemical_formula_sum            'C28 H34 N O2'
_chemical_formula_weight         416.56
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-C 2yc'
_space_group_name_H-M_alt        'C 1 2/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2020-09-16
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 100.410(5)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   49.281(20)
_cell_length_b                   8.517(3)
_cell_length_c                   11.787(4)
_cell_measurement_reflns_used    67.679
_cell_measurement_temperature    566(2)
_cell_measurement_theta_max      72.897
_cell_measurement_theta_min      5.279
_cell_volume                     4866(3)
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_temperature      566.3
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.976
_diffrn_measurement_device_type  'Bruker P4'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0710
_diffrn_reflns_av_unetI/netI     0.0525
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.976
_diffrn_reflns_limit_h_max       54
_diffrn_reflns_limit_h_min       -60
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            17931
_diffrn_reflns_point_group_measured_fraction_full 0.996
_diffrn_reflns_point_group_measured_fraction_max 0.976
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         72.679
_diffrn_reflns_theta_min         5.273
_exptl_absorpt_coefficient_mu    0.546
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            Colorless
_exptl_crystal_density_diffrn    1.137
_exptl_crystal_density_method    "'not measured'"
_exptl_crystal_description       Prism
_exptl_crystal_F_000             1800
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.2
_refine_diff_density_max         0.370
_refine_diff_density_min         -0.231
_refine_diff_density_rms         0.047
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.961
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     296
_refine_ls_number_reflns         4729
_refine_ls_number_restraints     2
_refine_ls_restrained_S_all      0.962
_refine_ls_R_factor_all          0.0804
_refine_ls_R_factor_gt           0.0621
_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^)+(0.1065P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1693
_refine_ls_wR_factor_ref         0.1887
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2886
_reflns_number_total             4729
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            2BEX-LIG.cif
_cod_data_source_block           2BEX-LIG
_cod_database_code               1559277
_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
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Rigid bond restraints
 C2, C7
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
 C2, C1
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
3.a Secondary CH2 refined with riding coordinates:
 C18(H18A,H18B), C17(H17A,H17B)
3.b Aromatic/amide H refined with riding coordinates:
 C15(H15), C12(H12), C6(H6), C4(H4), C3(H3), C7(H7)
3.c Idealised Me refined as rotating group:
 C20(H20A,H20B,H20C), C21(H21A,H21B,H21C), C23(H23A,H23B,H23C), C24(H24A,H24B,
 H24C), C22(H22A,H22B,H22C), C28(H28A,H28B,H28C), C25(H25A,H25B,H25C)
3.d Idealised tetrahedral OH refined as rotating group:
 O2(H2)
;
_shelx_res_checksum              634
_shelx_hkl_checksum              71016
_olex2_submission_special_instructions 'No special instructions were received'