Characterization of Conformationally Constrained Benzanilide Scaffolds for Potent and Selective HDAC8 Targeting.
Hassan, Muhammad Murtaza; Israelian, Johan; Nawar, Nabanita; Ganda, Giovanni; Manaswiyoungkul, Pimyupa; Raouf, Yasir; Armstrong, David; Sedighi, Abootaleb; Olaoye, Olasunkanmi O.; Erdogan, Fettah; Cabral, Aaron D.; Angeles, Fabrizio; Altintas, Rabia; de Araujo, Elvin D.; Gunning, Patrick Thomas; Journal of medicinal chemistry  (2020) –; doi:10.1021/acs.jmedchem.0c01025

data_1558720
_publ_section_title
;
 Characterization of Conformationally Constrained Benzanilide Scaffolds
 for Potent and Selective HDAC8 Targeting.
;
_journal_name_full               'Journal of medicinal chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.0c01025
_journal_year                    2020
_chemical_formula_moiety         'C22 H26 N2 O3'
_chemical_formula_sum            'C22 H26 N2 O3'
_chemical_formula_weight         366.45
_space_group_crystal_system      orthorhombic
_space_group_IT_number           56
_space_group_name_Hall           '-P 2ab 2ac'
_space_group_name_H-M_alt        'P c c n'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2018/3
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   21.4182(5)
_cell_length_b                   22.3478(5)
_cell_length_c                   9.3093(2)
_cell_measurement_reflns_used    9959
_cell_measurement_temperature    150(2)
_cell_measurement_theta_max      66.56
_cell_measurement_theta_min      2.86
_cell_volume                     4455.89(17)
_computing_cell_refinement       APEX3
_computing_data_collection       'APEX3 (Bruker, 2018)'
_computing_data_reduction        'SAINT (Bruker, 2014)'
_computing_molecular_graphics    'PLATON (Spek, 2009)'
_computing_publication_material  'SHELXTL (Sheldrick, 2008)'
_computing_structure_refinement  'SHELXL-2018/3 (Sheldrick, 2015b)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2015a)'
_diffrn_ambient_temperature      150(2)
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.988
_diffrn_measurement_device_type  'Bruker Kappa APEX-DUO CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.1360
_diffrn_reflns_av_unetI/netI     0.0518
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.988
_diffrn_reflns_limit_h_max       25
_diffrn_reflns_limit_h_min       -25
_diffrn_reflns_limit_k_max       26
_diffrn_reflns_limit_k_min       -26
_diffrn_reflns_limit_l_max       9
_diffrn_reflns_limit_l_min       -10
_diffrn_reflns_number            91022
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         68.152
_diffrn_reflns_theta_min         2.858
_diffrn_source                   'Bruker ImuS with multi-layr optics'
_exptl_absorpt_coefficient_mu    0.584
_exptl_absorpt_correction_T_max  0.7530
_exptl_absorpt_correction_T_min  0.5770
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Krause et al., 2015)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.092
_exptl_crystal_description       needle
_exptl_crystal_F_000             1568
_exptl_crystal_size_max          0.330
_exptl_crystal_size_mid          0.040
_exptl_crystal_size_min          0.040
_refine_diff_density_max         0.357
_refine_diff_density_min         -0.264
_refine_diff_density_rms         0.105
_refine_ls_extinction_coef       0.0027(2)
_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   1.111
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     256
_refine_ls_number_reflns         4026
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.111
_refine_ls_R_factor_all          0.0686
_refine_ls_R_factor_gt           0.0576
_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^)+(0.0368P)^2^+3.6283P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1313
_refine_ls_wR_factor_ref         0.1379
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3315
_reflns_number_total             4026
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm0c01025_si_003.cif
_cod_data_source_block           d19127_a_sq
_cod_database_code               1558720
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_min   0.831
_shelx_estimated_absorpt_t_max   0.977
_shelx_res_checksum              10748
_shelx_hkl_checksum              16877
_shelx_fab_checksum              36425