Design, synthesis of 2-phenyl-1H-benzo[d]imidazole derivatives as 17β-HSD10 inhibitor for the treatment of Alzheimer's Disease
liu, Xiaohan; zhou, bin; Chen, Yan; lin, Jinyuan; shao, Chenwen; Chen, Liuzeng; Ruan, Banfeng; zhang, xingxing; Qian, Yong; RSC Medicinal Chemistry  (2025) –; doi:10.1039/D4MD00861H

data_7250010
_publ_section_title
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 Design, synthesis of 2-phenyl-1H-benzo[d]imidazole derivatives as
 17\b-HSD10 inhibitor for the treatment of Alzheimer's Disease
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_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D4MD00861H
_journal_year                    2025
_chemical_formula_moiety         'C23 H25 F2 N3 O, H2 O'
_chemical_formula_sum            'C23 H27 F2 N3 O2'
_chemical_formula_weight         415.47
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2024-05-28
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-09-23 deposited with the CCDC.	2025-02-21 downloaded from the CCDC.
;
_cell_angle_alpha                80.809(8)
_cell_angle_beta                 89.290(7)
_cell_angle_gamma                78.757(8)
_cell_formula_units_Z            2
_cell_length_a                   7.1699(13)
_cell_length_b                   10.430(2)
_cell_length_c                   15.039(3)
_cell_measurement_reflns_used    4041
_cell_measurement_temperature    223.00
_cell_measurement_theta_max      26.890
_cell_measurement_theta_min      2.615
_cell_volume                     1088.7(4)
_computing_cell_refinement       'SAINT V8.40B (?, 2016)'
_computing_data_reduction        'SAINT V8.40B (?, 2016)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      223.00
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.989
_diffrn_measurement_device_type  'Bruker D8 VENTURE'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0737
_diffrn_reflns_av_unetI/netI     0.0432
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.989
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            28915
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.989
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.475
_diffrn_reflns_theta_min         2.017
_diffrn_source_current           1.4
_diffrn_source_power             0.07
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.093
_exptl_absorpt_correction_T_max  0.7456
_exptl_absorpt_correction_T_min  0.6873
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1038 before and 0.0711 after correction.
The Ratio of minimum to maximum transmission is 0.9218.
The \l/2 correction factor is Not present.
;
_exptl_crystal_density_diffrn    1.267
_exptl_crystal_description       block
_exptl_crystal_F_000             440
_exptl_crystal_size_max          0.13
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.266
_refine_diff_density_min         -0.247
_refine_diff_density_rms         0.046
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.035
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     277
_refine_ls_number_reflns         4943
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.035
_refine_ls_R_factor_all          0.0711
_refine_ls_R_factor_gt           0.0479
_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^)+(0.0525P)^2^+0.4167P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1155
_refine_ls_wR_factor_ref         0.1373
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3532
_reflns_number_total             4943
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4md00861h2.cif
_cod_data_source_block           mo_20240527_wq_hfu_2024_0227_2
_cod_database_code               7250010
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.991
_shelx_estimated_absorpt_t_min   0.988
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H,H) groups
2.a Free rotating group:
 O2(H2A,H2B)
2.b Ternary CH refined with riding coordinates:
 C18(H18)
2.c Secondary CH2 refined with riding coordinates:
 C19(H19A,H19B), C20(H20A,H20B), C22(H22A,H22B), C23(H23A,H23B)
2.d Aromatic/amide H refined with riding coordinates:
 N3(H3), C3(H3A), C7(H7), C12(H12), C13(H13), C15(H15), C16(H16)
2.e Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C), C8(H8A,H8B,H8C), C9(H9A,H9B,H9C)
;
_shelx_res_checksum              19337
_shelx_hkl_checksum              87967
_olex2_submission_special_instructions 'No special instructions were received'