Identification of ligand linkage vectors for the development of p300/CBP degraders
Brownsey, Duncan K.; Rowley, Ben C.; Gorobets, Evgueni; Mihara, Koichiro; Maity, Ranjan; Papatzimas, James W.; Gelfand, Benjamin S.; Hollenberg, Morley D.; Bahlis, Nizar J.; Derksen, Darren J.; RSC Medicinal Chemistry  (2022) –; doi:10.1039/D1MD00070E

data_7244894
_publ_section_title
;
 Identification of ligand linkage vectors for the development of p300/CBP
 degraders
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D1MD00070E
_journal_year                    2022
_chemical_absolute_configuration syn
_chemical_formula_moiety         'C10 H18 F3 N O S, H2 O'
_chemical_formula_sum            'C10 H20 F3 N O2 S'
_chemical_formula_weight         275.33
_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
_atom_sites_solution_primary     dual
_audit_creation_date             2020-07-06
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2021-03-04 deposited with the CCDC.	2022-04-12 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.0280(5)
_cell_length_b                   12.5634(8)
_cell_length_c                   18.7272(16)
_cell_measurement_reflns_used    3931
_cell_measurement_temperature    173
_cell_measurement_theta_max      65.192
_cell_measurement_theta_min      4.723
_cell_volume                     1418.25(19)
_computing_cell_refinement       'SAINT v8.37A (Bruker, 2015)'
_computing_data_reduction        'SAINT v8.37A (Bruker, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      173
_diffrn_measured_fraction_theta_full 0.990
_diffrn_measured_fraction_theta_max 0.990
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0431
_diffrn_reflns_av_unetI/netI     0.0520
_diffrn_reflns_Laue_measured_fraction_full 0.990
_diffrn_reflns_Laue_measured_fraction_max 0.990
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            6416
_diffrn_reflns_point_group_measured_fraction_full 0.988
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        65.188
_diffrn_reflns_theta_max         65.188
_diffrn_reflns_theta_min         4.237
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    2.301
_exptl_absorpt_correction_T_max  0.8641
_exptl_absorpt_correction_T_min  0.7053
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1091 before and 0.0462 after correction. The Ratio of minimum to maximum transmission is 0.8162. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.289
_exptl_crystal_description       plate
_exptl_crystal_F_000             584
_exptl_crystal_size_max          0.386
_exptl_crystal_size_mid          0.173
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.256
_refine_diff_density_min         -0.262
_refine_diff_density_rms         0.051
_refine_ls_abs_structure_details
;
 Flack x determined using 741 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.01(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.044
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     166
_refine_ls_number_reflns         2391
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.044
_refine_ls_R_factor_all          0.0514
_refine_ls_R_factor_gt           0.0427
_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^)+(0.0541P)^2^+0.2652P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1056
_refine_ls_wR_factor_ref         0.1104
_reflns_Friedel_coverage         0.689
_reflns_Friedel_fraction_full    0.984
_reflns_Friedel_fraction_max     0.984
_reflns_number_gt                2080
_reflns_number_total             2391
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d1md00070e2.cif
_cod_data_source_block           db-3-273
_cod_database_code               7244894
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.894
_shelx_estimated_absorpt_t_min   0.470
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C5(H5)
2.b Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C4(H4A,H4B)
2.c Aromatic/amide H refined with riding coordinates:
 C2(H2)
2.d X=CH2 refined with riding coordinates:
 C1(H1A,H1B)
2.e Idealised Me refined as rotating group:
 C8(H8A,H8B,H8C), C9(H9A,H9B,H9C), C10(H10A,H10B,H10C)
;
_shelx_res_checksum              97015
_olex2_submission_special_instructions 'No special instructions were received'