Synthesis and Characterization of the Selective, Reversible PKC<sub>β</sub> Inhibitor (9 S)-9-[(Dimethylamino)methyl]-6,7,10,11-tetrahydro-9 H,18 H-5,21:12,17-dimethenodibenzo[ e,k]pyrrolo[3,4- h][1,4,13]oxadiazacyclohexadecine-18,20(19 H)-dione, Ruboxistaurin (LY333531).
Lewin, Anita H.; Brieaddy, Larry; Deschamps, Jeffrey R.; Imler, Gregory H.; Mascarella, S. Wayne; Reddy, P. Anantha; Carroll, F. Ivy; ACS chemical neuroscience 10 (2019) 246–251; doi:10.1021/acschemneuro.8b00196

data_4515829
_publ_section_title
;
 Synthesis and Characterization of the Selective, Reversible
 PKC<sub>\b</sub> Inhibitor (9
 S)-9-[(Dimethylamino)methyl]-6,7,10,11-tetrahydro-9 H,18
 H-5,21:12,17-dimethenodibenzo[ e,k]pyrrolo[3,4-
 h][1,4,13]oxadiazacyclohexadecine-18,20(19 H)-dione, Ruboxistaurin
 (LY333531).
;
_journal_issue                   1
_journal_name_full               'ACS chemical neuroscience'
_journal_page_first              246
_journal_page_last               251
_journal_paper_doi               10.1021/acschemneuro.8b00196
_journal_volume                  10
_journal_year                    2019
_chemical_formula_moiety         'C28 H28 N4 O3'
_chemical_formula_sum            'C28 H28 N4 O3'
_chemical_formula_weight         468.54
_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
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                90
_cell_angle_beta                 90.0670(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.2036(2)
_cell_length_b                   22.0461(5)
_cell_length_c                   11.8589(3)
_cell_measurement_reflns_used    9976
_cell_measurement_temperature    150(2)
_cell_measurement_theta_max      74.717
_cell_measurement_theta_min      3.728
_cell_volume                     2406.21(10)
_computing_cell_refinement       'Bruker APEX3 v2015.5-2 (Bruker, 2015)'
_computing_data_collection       'Bruker APEX3 v2015.5-2 (Bruker, 2015)'
_computing_data_reduction
;
Bruker SAINT v8.34A (Bruker, 2013), Bruker XPREP v2014/2 (Bruker, 2014)
;
_computing_molecular_graphics    'Bruker SHELXTL v2014/7 (Bruker, 2014)'
_computing_publication_material  'Bruker SHELXTL v2014/7 (Bruker, 2014)'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_structure_solution    'Bruker SHELXTL v2014/7 (Bruker, 2014)'
_diffrn_ambient_temperature      150(2)
_diffrn_measured_fraction_theta_full 0.892
_diffrn_measured_fraction_theta_max 0.855
_diffrn_measurement_device_type  'Photon 100'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_monochromator  'HELIOS multilayer optics'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0396
_diffrn_reflns_av_unetI/netI     0.0574
_diffrn_reflns_Laue_measured_fraction_full 0.892
_diffrn_reflns_Laue_measured_fraction_max 0.855
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       27
_diffrn_reflns_limit_k_min       -24
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            12343
_diffrn_reflns_point_group_measured_fraction_full 0.790
_diffrn_reflns_point_group_measured_fraction_max 0.742
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         74.711
_diffrn_reflns_theta_min         3.727
_diffrn_source                   '1uS microfocus'
_exptl_absorpt_coefficient_mu    0.688
_exptl_absorpt_correction_T_max  0.7538
_exptl_absorpt_correction_T_min  0.5956
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS v2014/5 (Bruker, 2008)'
_exptl_crystal_colour            'clear orange'
_exptl_crystal_density_diffrn    1.293
_exptl_crystal_description       plate
_exptl_crystal_F_000             992
_exptl_crystal_size_max          0.491
_exptl_crystal_size_mid          0.106
_exptl_crystal_size_min          0.010
_refine_diff_density_max         0.957
_refine_diff_density_min         -0.621
_refine_diff_density_rms         0.093
_refine_ls_abs_structure_details
;
 Flack x determined using 2326 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.22(15)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.082
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     635
_refine_ls_number_reflns         7345
_refine_ls_number_restraints     24
_refine_ls_restrained_S_all      1.083
_refine_ls_R_factor_all          0.1017
_refine_ls_R_factor_gt           0.0917
_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^)+(0.0772P)^2^+5.9481P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2143
_refine_ls_wR_factor_ref         0.2226
_reflns_Friedel_coverage         0.691
_reflns_Friedel_fraction_full    0.683
_reflns_Friedel_fraction_max     0.624
_reflns_number_gt                6582
_reflns_number_total             7345
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            cn8b00196_si_002.cif
_cod_data_source_block           rti149
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               4515829
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_min   0.729
_shelx_estimated_absorpt_t_max   0.993
_shelx_res_checksum              48586
_shelx_hkl_checksum              66512