Design and SAR of withangulatin A analogs that act as covalent TrxR inhibitors through Michael addition reaction showing potential in cancer treatment.
Wang, Cheng; Li, Shang; Zhao, Jinhua; Yang, Huali; Yin, Fucheng; Ding, Ming; Luo, Jianguang; Wang, Xiao-Bing; Kong, Ling-Yi; Journal of medicinal chemistry  (2020) –; doi:10.1021/acs.jmedchem.0c01128

data_1559109
_publ_section_title
;
 Design and SAR of withangulatin A analogs that act as covalent TrxR
 inhibitors through Michael addition reaction showing potential in cancer
 treatment.
;
_journal_name_full               'Journal of medicinal chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.0c01128
_journal_year                    2020
_chemical_formula_sum            'C30 H38 O9'
_chemical_formula_weight         542.60
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.4020(2)
_cell_length_b                   13.4298(4)
_cell_length_c                   26.9766(9)
_cell_measurement_temperature    130(2)
_cell_volume                     2681.67(14)
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_diffrn_ambient_temperature      130(2)
_diffrn_measured_fraction_theta_full 0.992
_diffrn_measured_fraction_theta_max 0.990
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0737
_diffrn_reflns_av_unetI/netI     0.0636
_diffrn_reflns_Laue_measured_fraction_full 0.992
_diffrn_reflns_Laue_measured_fraction_max 0.990
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       31
_diffrn_reflns_limit_l_min       -33
_diffrn_reflns_number            20906
_diffrn_reflns_point_group_measured_fraction_full 0.990
_diffrn_reflns_point_group_measured_fraction_max 0.981
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         74.505
_diffrn_reflns_theta_min         3.276
_exptl_absorpt_coefficient_mu    0.814
_exptl_crystal_density_diffrn    1.344
_exptl_crystal_F_000             1160
_exptl_crystal_size_max          0.120
_exptl_crystal_size_mid          0.080
_exptl_crystal_size_min          0.030
_refine_diff_density_max         0.276
_refine_diff_density_min         -0.247
_refine_diff_density_rms         0.053
_refine_ls_abs_structure_details
;
 Flack x determined using 1642 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.05(14)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.995
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     366
_refine_ls_number_reflns         5373
_refine_ls_number_restraints     2
_refine_ls_restrained_S_all      0.995
_refine_ls_R_factor_all          0.0644
_refine_ls_R_factor_gt           0.0468
_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^)+(0.0363P)^2^+1.6445P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0996
_refine_ls_wR_factor_ref         0.1108
_reflns_Friedel_coverage         0.735
_reflns_Friedel_fraction_full    0.989
_reflns_Friedel_fraction_max     0.969
_reflns_number_gt                4445
_reflns_number_total             5373
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm0c01128_si_002.cif
_cod_data_source_block           20180716-3-1_0m
_cod_database_code               1559109
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_min   0.909
_shelx_estimated_absorpt_t_max   0.976
_shelx_res_checksum              13289
_shelx_hkl_checksum              14753