Discovery of (S)-3'-hydroxyblebbistatin and (S)-3'-aminoblebbistatin: polar myosin II inhibitors with superior research tool properties.
Verhasselt, Sigrid; Roman, Bart I.; De Wever, Olivier; Van Hecke, Kristof; Van Deun, Rik; Bracke, Marc E.; Stevens, Christian V.; Organic & biomolecular chemistry 15 (2017) 2104–2118; doi:10.1039/c7ob00006e

data_7155489
_publ_section_title
;
 Discovery of (S)-3'-hydroxyblebbistatin and (S)-3'-aminoblebbistatin:
 polar myosin II inhibitors with superior research tool properties.
;
_journal_issue                   9
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              2104
_journal_page_last               2118
_journal_paper_doi               10.1039/c7ob00006e
_journal_volume                  15
_journal_year                    2017
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C18 H16 N2 O3'
_chemical_formula_sum            'C18 H16 N2 O3'
_chemical_formula_weight         308.33
_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'
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2015-12-08
_audit_creation_method
;
Olex2 1.2
(compiled 2015.09.30 svn.r3233 for OlexSys, GUI svn.r5103)
;
_audit_update_record
;
2016-06-15 deposited with the CCDC.
2017-02-07 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   4.88084(6)
_cell_length_b                   14.45507(15)
_cell_length_c                   20.3743(2)
_cell_measurement_reflns_used    19410
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      75.3000
_cell_measurement_theta_min      3.6980
_cell_volume                     1437.47(3)
_computing_cell_refinement       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.41 (Rigaku OD, 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    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.0(1)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.4839
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.995
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w   -117.00 -51.00   1.00    1.00    --  -41.80-157.00-168.00   66
  2  \w    -49.00  33.00   1.00    1.00    --  -41.80  36.00-147.00   82
  3  \w     97.00 178.00   1.00    5.00    --  109.13 119.00  72.00   81
  4  \w     99.00 178.00   1.00    5.00    --  109.13  87.00  -5.00   79
  5  \w     34.00  92.00   1.00    5.00    --  109.13 -36.00  55.00   58
  6  \w   -114.00 -14.00   1.00    1.00    --  -41.80 -57.00  60.00  100
  7  \w     23.00  98.00   1.00    1.00    --   41.80-125.00-150.00   75
  8  \w     33.00  91.00   1.00    5.00    --  109.13 -30.00 120.00   58
  9  \w     36.00  98.00   1.00    5.00    --  109.13 -45.00 -90.00   62
 10  \w     36.00  98.00   1.00    5.00    --  109.13 -45.00   0.00   62
 11  \w    -70.00  31.00   1.00    1.00    --  -41.80  57.00  90.00  101
 12  \w   -114.00 -14.00   1.00    1.00    --  -41.80 -57.00 150.00  100
 13  \w   -114.00 -14.00   1.00    1.00    --  -41.80 -57.00 -60.00  100
 14  \w   -118.00  -9.00   1.00    1.00    --  -41.80 -77.00-120.00  109
 15  \w     81.00 178.00   1.00    5.00    --  109.13  30.00  90.00   97
 16  \w     81.00 178.00   1.00    5.00    --  109.13  30.00 -60.00   97
 17  \w     81.00 178.00   1.00    5.00    --  109.13  30.00-180.00   97
 18  \w     36.00 121.00   1.00    5.00    --  109.13-125.00-180.00   85
 19  \w   -118.00  -9.00   1.00    1.00    --  -41.80 -77.00  60.00  109
 20  \w    -70.00  31.00   1.00    1.00    --  -41.80  57.00 -30.00  101
 21  \w      9.00 118.00   1.00    1.00    --   41.80  77.00  60.00  109
 22  \w      9.00 118.00   1.00    1.00    --   41.80  77.00-180.00  109
 23  \w     80.00 178.00   1.00    5.00    --  109.13  61.00   0.00   98
 24  \w     26.00 109.00   1.00    5.00    --  109.13 -94.00  30.00   83
 25  \w     85.00 178.00   1.00    5.00    --  109.13  36.00-147.00   93
 26  \w     36.00  98.00   1.00    5.00    --  109.13 -45.00-150.00   62
 27  \w   -118.00  -9.00   1.00    1.00    --  -41.80 -77.00 -90.00  109
 28  \w   -116.00 -17.00   1.00    1.00    --  -41.80 -38.00 -90.00   99
 29  \w   -116.00 -17.00   1.00    1.00    --  -41.80 -38.00  90.00   99
 30  \w     17.00 116.00   1.00    1.00    --   41.80  38.00 -30.00   99
 31  \w     83.00 178.00   1.00    5.00    --  109.13  45.00-120.00   95
 32  \w     77.00 178.00   1.00    5.00    --  109.13  77.00 -60.00  101
 33  \w     83.00 178.00   1.00    5.00    --  109.13  45.00 120.00   95
 34  \w     80.00 178.00   1.00    5.00    --  109.13  61.00  30.00   98
 35  \w   -114.00 -14.00   1.00    1.00    --  -41.80 -57.00-120.00  100
 36  \w   -114.00 -14.00   1.00    1.00    --  -41.80 -57.00 -30.00  100
 37  \w      9.00 118.00   1.00    1.00    --   41.80  77.00 120.00  109
 38  \w      9.00 118.00   1.00    1.00    --   41.80  77.00 -60.00  109
 39  \w     80.00 178.00   1.00    5.00    --  109.13  61.00 -30.00   98
 40  \w     77.00 178.00   1.00    5.00    --  109.13  77.00  60.00  101
 41  \w     26.00 109.00   1.00    5.00    --  109.13 -94.00-150.00   83
 42  \w     80.00 178.00   1.00    5.00    --  109.13  61.00 -60.00   98
 43  \w    -46.00 130.00   1.00    1.00    --   41.80   0.00-120.00  176
 44  \w    -46.00 130.00   1.00    1.00    --   41.80   0.00-150.00  176
 45  \w    -46.00 130.00   1.00    1.00    --   41.80   0.00-180.00  176
 46  \w      9.00 118.00   1.00    1.00    --   41.80  77.00 -30.00  109
 47  \w     77.00 178.00   1.00    5.00    --  109.13  77.00 150.00  101
 48  \w     80.00 178.00   1.00    5.00    --  109.13  61.00-120.00   98
 49  \w     80.00 178.00   1.00    5.00    --  109.13  61.00 120.00   98
 50  \w     80.00 178.00   1.00    5.00    --  109.13  61.00-150.00   98
 51  \w    -46.00 130.00   1.00    1.00    --   41.80   0.00 -90.00  176
 52  \w    -46.00 130.00   1.00    1.00    --   41.80   0.00 -30.00  176
 53  \w    -46.00 130.00   1.00    1.00    --   41.80   0.00   0.00  176
 54  \w    -46.00 130.00   1.00    1.00    --   41.80   0.00 -60.00  176
 55  \w     77.00 178.00   1.00    5.00    --  109.13  77.00   0.00  101
 56  \w     77.00 178.00   1.00    5.00    --  109.13  77.00  30.00  101
 57  \w     77.00 178.00   1.00    5.00    --  109.13  77.00 -90.00  101
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0995591000
_diffrn_orient_matrix_UB_12      0.0923314000
_diffrn_orient_matrix_UB_13      0.0292292000
_diffrn_orient_matrix_UB_21      0.1039448000
_diffrn_orient_matrix_UB_22      0.0513643000
_diffrn_orient_matrix_UB_23      -0.0614035000
_diffrn_orient_matrix_UB_31      -0.2808556000
_diffrn_orient_matrix_UB_32      -0.0137427000
_diffrn_orient_matrix_UB_33      -0.0331266000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.1088
_diffrn_reflns_av_unetI/netI     0.0314
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -25
_diffrn_reflns_number            49208
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.993
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.381
_diffrn_reflns_theta_min         3.749
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.803
_exptl_absorpt_correction_T_max  0.994
_exptl_absorpt_correction_T_min  0.972
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
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            'clear orange'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    orange
_exptl_crystal_density_diffrn    1.425
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       plate
_exptl_crystal_F_000             648
_exptl_crystal_size_max          0.397
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.065
_refine_diff_density_max         0.507
_refine_diff_density_min         -0.341
_refine_diff_density_rms         0.066
_refine_ls_abs_structure_details
;
 Flack x determined using 1094 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.14(12)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.074
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     211
_refine_ls_number_reflns         2950
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.074
_refine_ls_R_factor_all          0.0527
_refine_ls_R_factor_gt           0.0498
_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^)+(0.0991P)^2^+0.2585P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1346
_refine_ls_wR_factor_ref         0.1386
_reflns_Friedel_coverage         0.684
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.991
_reflns_number_gt                2768
_reflns_number_total             2950
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7ob00006e2.cif
_cod_data_source_block           cs032
_cod_depositor_comments
'Adding full bibliography for 7155488--7155489.cif.'
_cod_database_code               7155489
_shelxl_version_number           2013-4
_chemical_oxdiff_formula         'C18 H16 N2 O3'
_reflns_odcompleteness_completeness 99.94
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_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) groups
2.a Secondary CH2 refined with riding coordinates:
 C11(H11A,H11B), C12(H12A,H12B)
2.b Aromatic/amide H refined with riding coordinates:
 C2(H2A), C3(H3A), C5(H5), C14(H14), C16(H16), C17(H17), C18(H18)
2.c Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C)
2.d Idealised tetrahedral OH refined as rotating group:
 O2(H2), O3(H3)
;
_shelx_res_checksum              47646
_olex2_exptl_crystal_mounting_method 'mounted on a nylon loop'
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.716
_oxdiff_exptl_absorpt_empirical_full_min 0.541