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_4517472
_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            'C16 H18 N2 O'
_chemical_formula_weight         254.32
_chemical_name_common            9
_chemical_name_systematic        9
_space_group.centring_type       primitive
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     iterative
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2018/3
_cell_angle_alpha                90
_cell_angle_beta                 111.019(5)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   10.7972(5)
_cell_length_b                   4.73210(10)
_cell_length_c                   13.9575(6)
_cell_measurement_reflns_used    8522
_cell_measurement_temperature    90(2)
_cell_measurement_theta_max      74.4630
_cell_measurement_theta_min      3.3790
_cell_volume                     665.69(5)
_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 1.000
_diffrn_measured_fraction_theta_max 0.972
_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  0.0389
_diffrn_reflns_av_unetI/netI     0.0236
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.972
_diffrn_refln_scan_rate          0.05
_diffrn_refln_scan_width         0.5
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       5
_diffrn_reflns_limit_k_min       -5
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            13517
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.953
_diffrn_reflns_theta_full        67.000
_diffrn_reflns_theta_max         74.741
_diffrn_reflns_theta_min         3.392
_diffrn_source                   'Rotating-anode X-ray tube'
_exptl_absorpt_coefficient_mu    0.631
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.626
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
; 
CrysAlisPro 1.171.40.35a (Rigaku Oxford Diffraction, 2018) 
Numerical absorption correction based on gaussian integration over 
   a multifaceted crystal model 
Empirical absorption correction using spherical harmonics, 
 implemented in SCALE3 ABSPACK scaling algorithm. 
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.269
_exptl_crystal_description       rod
_exptl_crystal_F_000             272
_exptl_crystal_size_max          0.070
_exptl_crystal_size_mid          0.030
_exptl_crystal_size_min          0.030
_refine_diff_density_max         0.189
_refine_diff_density_min         -0.144
_refine_diff_density_rms         0.031
_refine_ls_abs_structure_details
; 
 Flack x determined using 1065 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259). 
;
_refine_ls_abs_structure_Flack   -0.12(13)
_refine_ls_extinction_coef       0.0134(16)
_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   1.061
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     174
_refine_ls_number_reflns         2595
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.061
_refine_ls_R_factor_all          0.0289
_refine_ls_R_factor_gt           0.0285
_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^)+(0.0472P)^2^+0.0970P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0773
_refine_ls_wR_factor_ref         0.0777
_reflns_Friedel_coverage         0.740
_reflns_Friedel_fraction_full    0.994
_reflns_Friedel_fraction_max     0.929
_reflns_number_gt                2550
_reflns_number_total             2595
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml0c00004_si_004.cif
_cod_data_source_block           9
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               4517472
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_min   0.957
_shelx_estimated_absorpt_t_max   0.981
_shelx_res_checksum              96407
_shelx_hkl_checksum              88659