2-Aryl-1-hydroxyimidazoles possessing antiviral activity against wide range of orthopoxviruses including Variola virus.
Basanova, Elizaveta Ivanovna; Kulikova, Ekaterina; Bormotov, Nikolai I.; Serova, Olga; Shishkina, Larisa; Ovchinnikova, Alyona; Odnoshevskiy, Dmitry; Pyankov, Oleg; Agafonov, Alexander; Yarovaya, Olga; Borisevich, Sophia; Ilyina, Margarita; Kolybalov, Dmitry; Arkhipov, Sergey; Bogdanov, Nikita; Pavlova, Marina A.; Salakhutdinov, Nariman; Perevalov, Valery P.; Nikitina, Polina A.; RSC Medicinal Chemistry  (2024) –; doi:10.1039/D4MD00181H

data_7248985
_publ_section_title
;
 2-Aryl-1-hydroxyimidazoles possessing antiviral activity against wide
 range of orthopoxviruses including Variola virus.
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D4MD00181H
_journal_year                    2024
_chemical_formula_moiety         'C13 H11 F3 N2 O2'
_chemical_formula_sum            'C13 H11 F3 N2 O2'
_chemical_formula_weight         284.24
_chemical_name_systematic
'1-(1-hydroxy-4-methyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazol-5-yl)ethan-1-one 4-acetyl-5-methyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazole 3-oxide'
_space_group_crystal_system      monoclinic
_space_group_IT_number           9
_space_group_name_Hall           'I -2ya'
_space_group_name_H-M_alt        'I 1 a 1'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2024-03-14
_audit_creation_method
;
Olex2 1.5
(compiled 2022.04.07 svn.rca3783a0 for OlexSys, GUI svn.r6498)
;
_audit_update_record
;
2024-03-14 deposited with the CCDC.	2024-06-26 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 105.339(10)
_cell_angle_gamma                90
_cell_formula_units_Z            16
_cell_length_a                   15.7230(16)
_cell_length_b                   14.3769(9)
_cell_length_c                   23.665(2)
_cell_measurement_reflns_used    3313
_cell_measurement_temperature    295(4)
_cell_measurement_theta_max      25.1670
_cell_measurement_theta_min      2.9380
_cell_volume                     5158.9(8)
_computing_cell_refinement       'CrysAlisPro 1.171.41.120a (Rigaku OD, 2021)'
_computing_data_collection       'CrysAlisPro 1.171.41.120a (Rigaku OD, 2021)'
_computing_data_reduction        'CrysAlisPro 1.171.41.120a (Rigaku OD, 2021)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2017/1 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      295(4)
_diffrn_detector_area_resol_mean 5.8140
_diffrn_measured_fraction_theta_full 0.961
_diffrn_measured_fraction_theta_max 0.797
_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    -90.00  90.00   1.00  240.00    --    0.00   0.00  45.00  180
;
_diffrn_measurement_device       'abstract diffractometer'
_diffrn_measurement_device_type  'Tongda TD-5000'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0466
_diffrn_reflns_av_unetI/netI     0.0710
_diffrn_reflns_Laue_measured_fraction_full 0.961
_diffrn_reflns_Laue_measured_fraction_max 0.797
_diffrn_reflns_limit_h_max       20
_diffrn_reflns_limit_h_min       -20
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       30
_diffrn_reflns_limit_l_min       -30
_diffrn_reflns_number            16053
_diffrn_reflns_point_group_measured_fraction_full 0.903
_diffrn_reflns_point_group_measured_fraction_max 0.736
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         28.227
_diffrn_reflns_theta_min         2.805
_exptl_absorpt_coefficient_mu    0.129
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.69583
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.120a (Rigaku Oxford Diffraction, 2021)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.464
_exptl_crystal_description       plate
_exptl_crystal_F_000             2336
_exptl_crystal_preparation       'chemical sythesis'
_exptl_crystal_recrystallization_method 'slow evaporation toluene solution'
_exptl_crystal_size_max          0.03
_exptl_crystal_size_mid          0.025
_exptl_crystal_size_min          0.01
_refine_diff_density_max         0.122
_refine_diff_density_min         -0.149
_refine_diff_density_rms         0.030
_refine_ls_abs_structure_details
;
 Flack x determined using 1924 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.9(6)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.001
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     836
_refine_ls_number_reflns         9353
_refine_ls_number_restraints     25
_refine_ls_restrained_S_all      1.001
_refine_ls_R_factor_all          0.0993
_refine_ls_R_factor_gt           0.0515
_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^)+(0.0534P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1119
_refine_ls_wR_factor_ref         0.1299
_reflns_Friedel_coverage         0.846
_reflns_Friedel_fraction_full    0.845
_reflns_Friedel_fraction_max     0.675
_reflns_number_gt                5585
_reflns_number_total             9353
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4md00181h2.cif
_cod_data_source_block           4c_pani114_phme
_cod_original_cell_volume        5159.0(8)
_cod_database_code               7248985
_shelx_shelxl_version_number     2017/1
_shelx_estimated_absorpt_t_max   0.999
_shelx_estimated_absorpt_t_min   0.996
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Restrained distances
 F6-C1 \\sim F5-C1
 with sigma of 0.02
 F4-C1 \\sim F3-C1
 with sigma of 0.02
 F2-C1 \\sim F1-C1
 with sigma of 0.02
 F18-C1D \\sim F13-C1D
 with sigma of 0.02
 F16-C1D \\sim F17-C1D
 with sigma of 0.02
 F14-C1D \\sim F15-C1D
 with sigma of 0.02
 F9-C1B \\sim F10-C1B
 with sigma of 0.02
 F7-C1B \\sim F8-C1B
 with sigma of 0.02
 F11-C1B \\sim F12-C1B
 with sigma of 0.02
 F22-C1C \\sim F21-C1C
 with sigma of 0.02
 F20-C1C \\sim F19-C1C
 with sigma of 0.02
3. Rigid body (RIGU) restrains
 F13, C1D
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 F15, C1D
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 F17, C1D
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 F12, C1B
 with sigma for 1-2 distances of 0.002 and sigma for 1-3 distances of 0.002
4. Others
 Sof(F3)=Sof(F1)=Sof(F5)=1-FVAR(1)
 Sof(F6)=Sof(F2)=Sof(F4)=FVAR(1)
 Sof(F13)=Sof(F15)=Sof(F17)=1-FVAR(2)
 Sof(F18)=Sof(F14)=Sof(F16)=FVAR(2)
 Sof(F12)=Sof(F8)=Sof(F10)=1-FVAR(3)
 Sof(F11)=Sof(F9)=Sof(F7)=FVAR(3)
 Sof(F21)=Sof(F19)=1-FVAR(4)
 Sof(F20)=Sof(F22)=FVAR(4)
5.a Aromatic/amide H refined with riding coordinates:
 C6A(H6A), C3AD(H3AD), C6AB(H6AB), C2AD(H2AD), C6AC(H6AC), C5A(H5A),
 C2AC(H2AC), C6AD(H6AD), C5AC(H5AC), C5AD(H5AD), C2A(H2A), C3AC(H3AC),
 C5AB(H5AB), C2AB(H2AB), C3AB(H3AB), C3A(H3A)
5.b Idealised Me refined as rotating group:
 C7C(H7CA,H7CB,H7CC), C01T(H01A,H01B,H01C), C7D(H7DA,H7DB,H7DC), C7(H7A,H7B,
 H7C), C8B(H8BA,H8BB,H8BC), C8(H8A,H8B,H8C), C7B(H7BA,H7BB,H7BC), C8D(H8DA,H8DB,
 H8DC)
5.c Idealised tetrahedral OH refined as rotating group:
 O3B(H3B), O3D(H3D), O3(H3), O3C(H3C)
;
_shelx_res_checksum              9108
_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
;