The Optimization of a Novel, Weak Bromo and Extra Terminal Domain (BET) Bromodomain Fragment Ligand to a Potent and Selective Second Bromodomain (BD2) Inhibitor.
Seal, Jonathan T.; Atkinson, Stephen J.; Aylott, Helen; Bamborough, Paul; Chung, Chun-Wa; Copley, Royston C. B.; Gordon, Laurie; Grandi, Paola; Gray, James R. J.; Harrison, Lee A.; Hayhow, Thomas G.; Lindon, Matthew; Messenger, Cassie; Michon, Anne-Marie; Mitchell, Darren; Preston, Alex; Prinjha, Rab K.; Rioja, Inmaculada; Taylor, Simon; Wall, Ian D.; Watson, Robert J.; Woolven, James M.; Demont, Emmanuel H.; Journal of medicinal chemistry  (2020) –; doi:10.1021/acs.jmedchem.0c00796

data_1558935
_publ_section_title
;
 The Optimization of a Novel, Weak Bromo and Extra Terminal Domain (BET)
 Bromodomain Fragment Ligand to a Potent and Selective Second Bromodomain
 (BD2) Inhibitor.
;
_journal_name_full               'Journal of medicinal chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.0c00796
_journal_year                    2020
_chemical_formula_moiety         'C18 H19 N3 O3'
_chemical_formula_sum            'C18 H19 N3 O3'
_chemical_formula_weight         325.36
_chemical_name_systematic
;
1-Benzyl-N5-cyclopropyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide
;
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  '-P 2yn'
_symmetry_space_group_name_H-M   'P 1 21/n 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 97.299(3)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   13.4672(4)
_cell_length_b                   5.79643(15)
_cell_length_c                   20.7574(6)
_cell_measurement_reflns_used    3948
_cell_measurement_temperature    150(2)
_cell_measurement_theta_max      66.94
_cell_measurement_theta_min      3.69
_cell_volume                     1607.23(8)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.36.32 (release 02-08-2013 CrysAlis171 .NET)
(compiled Aug  2 2013,16:46:58)
;
_computing_data_collection
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CrysAlisPro, Agilent Technologies,
Version 1.171.36.32 (release 02-08-2013 CrysAlis171 .NET)
(compiled Aug  2 2013,16:46:58)
;
_computing_data_reduction
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CrysAlisPro, Agilent Technologies,
Version 1.171.36.32 (release 02-08-2013 CrysAlis171 .NET)
(compiled Aug  2 2013,16:46:58)
;
_computing_molecular_graphics    'SHELXTL V2008/4 (Bruker, 2008)'
_computing_publication_material  'SHELXTL V2008/4 (Bruker, 2008)'
_computing_structure_refinement  'SHELXTL V2008/4 (Bruker, 2008)'
_computing_structure_solution    'SHELXT (Sheldrick, 2014)'
_diffrn_ambient_temperature      150(2)
_diffrn_detector_area_resol_mean 10.3968
_diffrn_measured_fraction_theta_full 0.991
_diffrn_measured_fraction_theta_max 0.991
_diffrn_measurement_details
;
  1 omega  -34.00   75.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       41.5905  -77.0000  -60.0000 109

  2 omega   43.00  100.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       41.5905   38.0000   60.0000 57

  3 omega   51.00  125.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -93.0000 -122.2162 74

  4 omega   19.00   46.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -30.0000   30.0000 27

  5 omega   46.00   74.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -45.0000  -60.0000 28

  6 omega   33.00   75.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -43.0000  146.0000 42

  7 omega   84.00  109.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  125.0000 -180.0000 25

  8 omega   68.00  128.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000   30.0000   60.0000 60

  9 omega   35.00   61.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -94.0000  150.0000 26

 10 omega   25.00   50.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000 -125.0000   60.0000 25

 11 omega   60.00   85.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000 -125.0000   60.0000 25

 12 omega   84.00  168.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000   45.0000  -30.0000 84

 13 omega   36.00   68.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -45.0000 -180.0000 32

 14 omega   27.00   56.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -77.0000   60.0000 29

 15 omega   86.00  123.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -77.0000   60.0000 37

 16 omega   99.00  133.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -93.0000  -67.7535 34

 17 omega  141.00  167.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000   30.0000   60.0000 26

 18 omega   45.00   73.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -93.0000  -67.7535 28

 19 omega -116.00  -12.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -      -41.5905  -57.0000  -30.0000 104

 20 omega -116.00  -12.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -      -41.5905  -57.0000 -120.0000 104

 21 omega    8.00  120.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       41.5905   77.0000  150.0000 112

 22 omega   63.00  108.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000   61.0000 -180.0000 45

 23 omega   66.00  168.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000   45.0000  120.0000 102

 24 omega   16.00   69.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -       93.5000  -30.0000   60.0000 53
;
_diffrn_measurement_device_type  'Oxford Diffraction Gemini A Ultra'
_diffrn_measurement_method       'omega scans'
_diffrn_orient_matrix_UB_11      -0.0476023000
_diffrn_orient_matrix_UB_12      0.2106886000
_diffrn_orient_matrix_UB_13      0.0294244000
_diffrn_orient_matrix_UB_21      -0.0769074000
_diffrn_orient_matrix_UB_22      -0.1590992000
_diffrn_orient_matrix_UB_23      0.0265369000
_diffrn_orient_matrix_UB_31      0.0715633000
_diffrn_orient_matrix_UB_32      -0.0309522000
_diffrn_orient_matrix_UB_33      0.0634573000
_diffrn_radiation_collimation    '0.8 mm double-pinhole'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_source         'Enhance Ultra (Cu) X-ray Source'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0438
_diffrn_reflns_av_sigmaI/netI    0.0384
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       6
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            11968
_diffrn_reflns_theta_full        67.00
_diffrn_reflns_theta_max         67.00
_diffrn_reflns_theta_min         3.71
_exptl_absorpt_coefficient_mu    0.762
_exptl_absorpt_correction_T_max  0.992
_exptl_absorpt_correction_T_min  0.908
_exptl_absorpt_correction_type   analytical
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.36.32 (release 02-08-2013 CrysAlis171 .NET)
(compiled Aug  2 2013,16:46:58)
Analytical numeric absorption correction using a multifaceted crystal
model based on expressions derived by R.C. Clark & J.S. Reid.
(Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897)
;
_exptl_crystal_colour            Colourless
_exptl_crystal_density_diffrn    1.345
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       Needle
_exptl_crystal_F_000             688
_exptl_crystal_size_max          0.24
_exptl_crystal_size_mid          0.04
_exptl_crystal_size_min          0.01
_refine_diff_density_max         0.240
_refine_diff_density_min         -0.190
_refine_diff_density_rms         0.040
_refine_ls_extinction_coef       0.0012(2)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXTL V2008/4 (Bruker, 2008)'
_refine_ls_goodness_of_fit_ref   1.032
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     227
_refine_ls_number_reflns         2833
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.032
_refine_ls_R_factor_all          0.0566
_refine_ls_R_factor_gt           0.0384
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0430P)^2^+0.2719P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0861
_refine_ls_wR_factor_ref         0.0940
_reflns_number_gt                2170
_reflns_number_total             2833
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jm0c00796_si_004.cif
_cod_data_source_block           20
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_geom_angle_publ_flag' value 'Y' was changed to 'y' in
accordance with the
/home/data/users/saulius/crontab/automatic-downloads/rss-feeds/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26 (36 times).

data item '_geom_bond_publ_flag' value 'Y' was changed to 'y' in
accordance with the
/home/data/users/saulius/crontab/automatic-downloads/rss-feeds/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26 (26 times).

data item '_geom_torsion_publ_flag' value 'Y' was changed to 'y' in
accordance with the
/home/data/users/saulius/crontab/automatic-downloads/rss-feeds/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26 (44 times).

Automatic conversion script
Id: cif_fix_values 7556 2019-12-06 15:28:31Z antanas 
;
_cod_original_sg_symbol_H-M      'P 21/n'
_cod_database_code               1558935
_computing_data_merging          'SHELXTL V2008/4 (Bruker, 2008)'