Implementation of the CYP Index for the Design of Selective Tryptophan-2,3-dioxygenase Inhibitors
Parr, Brendan T.; Pastor, Richard; Sellers, Benjamin D.; Pei, Zhonghua; Jaipuri, Firoz A.; Castanedo, Georgette M.; Gazzard, Lewis; Kumar, Sanjeev; Li, Xiaokai; Liu, Wen; Mendonca, Rohan; Pavana, Roheeth K.; Potturi, Hima; Shao, Cheng; Velvadapu, Venkata; Waldo, Jesse P.; Wu, Guosheng; Yuen, Po-wai; Zhang, Zuhui; Zhang, Yamin; Harris, Seth F.; Oh, Angela J.; DiPasquale, Antonio; Dement, Kevin; La, Hank; Goon, Leanne; Gustafson, Amy; VanderPorten, Erica C.; Mautino, Mario R.; Liu, Yichin; ACS Medicinal Chemistry Letters  (2020) –; doi:10.1021/acsmedchemlett.0c00004

data_4517465
_publ_section_title
;
 Implementation of the CYP Index for the Design of Selective
 Tryptophan-2,3-dioxygenase Inhibitors
;
_journal_name_full               'ACS Medicinal Chemistry Letters'
_journal_paper_doi               10.1021/acsmedchemlett.0c00004
_journal_year                    2020
_chemical_absolute_configuration ad
_chemical_formula_sum            'C38 H55 Cl N4 O5'
_chemical_formula_weight         683.31
_chemical_name_common            8
_chemical_name_systematic        8
_space_group.centring_type       primitive
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     iterative
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2018/3
_cell_angle_alpha                73.148(2)
_cell_angle_beta                 77.8340(10)
_cell_angle_gamma                89.575(2)
_cell_formula_units_Z            1
_cell_length_a                   6.81630(10)
_cell_length_b                   9.5313(2)
_cell_length_c                   15.3468(2)
_cell_measurement_reflns_used    11606
_cell_measurement_temperature    90(2)
_cell_measurement_theta_max      74.0900
_cell_measurement_theta_min      3.0640
_cell_volume                     931.27(3)
_computing_cell_refinement       'CrysAlisPro 1.171.40.35a'
_computing_data_collection       'CrysAlisPro 1.171.40.35a'
_computing_data_reduction        'CrysAlisPro 1.171.40.35a'
_computing_molecular_graphics    ORTEP-32
_computing_publication_material  WinGX
_computing_structure_refinement  SHELXL-2018
_computing_structure_solution    SHELXT-2014
_diffrn_ambient_temperature      90(2)
_diffrn_detector_area_resol_mean 10.0000
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.940
_diffrn_measurement_device_type  'ROD, Synergy Custom system, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0255
_diffrn_reflns_av_unetI/netI     0.0264
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.940
_diffrn_refln_scan_rate          0.05
_diffrn_refln_scan_width         0.5
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            17678
_diffrn_reflns_point_group_measured_fraction_full 0.933
_diffrn_reflns_point_group_measured_fraction_max 0.862
_diffrn_reflns_theta_full        67.000
_diffrn_reflns_theta_max         75.128
_diffrn_reflns_theta_min         3.083
_diffrn_source                   'Rotating-anode X-ray tube'
_exptl_absorpt_coefficient_mu    1.278
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.83098
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
; 
CrysAlisPro 1.171.40.35a (Rigaku Oxford Diffraction, 2018) 
Empirical absorption correction using spherical harmonics, 
 implemented in SCALE3 ABSPACK scaling algorithm. 
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.218
_exptl_crystal_description       rod
_exptl_crystal_F_000             368
_exptl_crystal_size_max          0.080
_exptl_crystal_size_mid          0.050
_exptl_crystal_size_min          0.050
_refine_diff_density_max         0.476
_refine_diff_density_min         -0.486
_refine_diff_density_rms         0.047
_refine_ls_abs_structure_details
; 
 Flack x determined using 2845 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259). 
;
_refine_ls_abs_structure_Flack   0.050(7)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.053
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     437
_refine_ls_number_reflns         6643
_refine_ls_number_restraints     3
_refine_ls_restrained_S_all      1.053
_refine_ls_R_factor_all          0.0429
_refine_ls_R_factor_gt           0.0420
_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^)+(0.0634P)^2^+0.3943P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1122
_refine_ls_wR_factor_ref         0.1136
_reflns_Friedel_coverage         0.834
_reflns_Friedel_fraction_full    0.867
_reflns_Friedel_fraction_max     0.784
_reflns_number_gt                6495
_reflns_number_total             6643
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml0c00004_si_003.cif
_cod_data_source_block           8
_cod_database_code               4517465
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_min   0.905
_shelx_estimated_absorpt_t_max   0.939
_shelx_res_checksum              19387
_shelx_hkl_checksum              4594