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_7155488
_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             2015-12-05
_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                   4.87924(5)
_cell_length_b                   14.43858(15)
_cell_length_c                   20.3657(2)
_cell_measurement_reflns_used    26458
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      75.0550
_cell_measurement_theta_min      3.7080
_cell_volume                     1434.75(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 1.000
_diffrn_measured_fraction_theta_max 0.999
_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    -32.00  73.00   1.00    1.00    --   41.93 -70.00  -7.00  105
  2  \w     96.00 178.00   1.00    2.50    --  109.13  80.00-121.00   82
  3  \w     78.00 178.00   1.00    2.50    --  109.13  70.00 123.00  100
  4  \w     35.00 141.00   1.00    2.50    --  109.13 -72.00-132.00  106
  5  \w    -96.00  -2.00   1.00    1.00    --  -41.93 125.00 -60.00   94
  6  \w     23.00  98.00   1.00    1.00    --   41.93-125.00 120.00   75
  7  \w     23.00  98.00   1.00    1.00    --   41.93-125.00-120.00   75
  8  \w     33.00  91.00   1.00    2.50    --  109.13 -30.00-120.00   58
  9  \w     33.00  91.00   1.00    2.50    --  109.13 -30.00-180.00   58
 10  \w     33.00  91.00   1.00    2.50    --  109.13 -30.00 120.00   58
 11  \w   -116.00 -17.00   1.00    1.00    --  -41.93 -38.00-150.00   99
 12  \w   -118.00  -9.00   1.00    1.00    --  -41.93 -77.00 120.00  109
 13  \w   -116.00 -11.00   1.00    1.00    --  -41.93 -70.00  -7.00  105
 14  \w     36.00 121.00   1.00    2.50    --  109.13-125.00-180.00   85
 15  \w     81.00 178.00   1.00    2.50    --  109.13  30.00 -30.00   97
 16  \w     81.00 178.00   1.00    2.50    --  109.13  30.00  60.00   97
 17  \w     26.00 109.00   1.00    2.50    --  109.13 -94.00  30.00   83
 18  \w     83.00 178.00   1.00    2.50    --  109.13  45.00-120.00   95
 19  \w     77.00 178.00   1.00    2.50    --  109.13  77.00-180.00  101
 20  \w    -50.00  32.00   1.00    1.00    --  -41.93  38.00 -90.00   82
 21  \w   -118.00 -83.00   1.00    1.00    --  -41.93 -77.00 -30.00   35
 22  \w   -116.00 -11.00   1.00    1.00    --  -41.93 -72.00-132.00  105
 23  \w     63.00  88.00   1.00    2.50    --  109.13 -70.00  -7.00   25
 24  \w   -114.00 -14.00   1.00    1.00    --  -42.05 -57.00  30.00  100
 25  \w   -118.00  -9.00   1.00    1.00    --  -42.05 -77.00 -90.00  109
 26  \w    -50.00  32.00   1.00    1.00    --  -42.05  38.00-180.00   82
 27  \w   -114.00 -14.00   1.00    1.00    --  -42.05 -57.00  90.00  100
 28  \w   -118.00  -9.00   1.00    1.00    --  -42.05 -77.00   0.00  109
 29  \w   -114.00 -14.00   1.00    1.00    --  -42.05 -57.00 120.00  100
 30  \w      9.00 118.00   1.00    1.00    --   42.05  77.00 -60.00  109
 31  \w     11.00 116.00   1.00    1.00    --   42.05  72.00  -1.00  105
 32  \w     18.00 116.00   1.00    1.00    --   42.05  38.00-120.00   98
 33  \w     26.00 109.00   1.00    2.50    --  109.13 -94.00-150.00   83
 34  \w     80.00 178.00   1.00    2.50    --  109.13  61.00 -90.00   98
 35  \w     83.00 178.00   1.00    2.50    --  109.13  45.00-180.00   95
 36  \w     77.00 178.00   1.00    2.50    --  109.13  77.00 -30.00  101
 37  \w     80.00 178.00   1.00    2.50    --  109.13  61.00  60.00   98
 38  \w     80.00 178.00   1.00    2.50    --  109.13  61.00  90.00   98
 39  \w     36.00  98.00   1.00    2.50    --  109.13 -45.00   0.00   62
 40  \w     77.00 178.00   1.00    2.50    --  109.13  77.00 -60.00  101
 41  \w     78.00 178.00   1.00    2.50    --  109.13  72.00  -1.00  100
 42  \w   -122.00  -1.00   1.00    1.00    --  -42.05 -19.00  60.00  121
 43  \w     63.00  88.00   1.00    2.50    --  109.13 -70.00  -7.00   25
 44  \w   -114.00 -14.00   1.00    1.00    --  -42.05 -57.00-150.00  100
 45  \w   -114.00 -14.00   1.00    1.00    --  -42.05 -57.00 150.00  100
 46  \w     18.00 116.00   1.00    1.00    --   42.05  38.00 -60.00   98
 47  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00 -90.00  176
 48  \w      9.00 118.00   1.00    1.00    --   42.05  77.00 120.00  109
 49  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00-180.00  176
 50  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00-120.00  176
 51  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00-150.00  176
 52  \w     18.00 116.00   1.00    1.00    --   42.05  38.00 150.00   98
 53  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00 -60.00  176
 54  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00 -30.00  176
 55  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00   0.00  176
 56  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00  30.00  176
 57  \w    -46.00 114.00   1.00    1.00    --   42.05   0.00  60.00  160
 58  \w     18.00 116.00   1.00    1.00    --   42.05  38.00-180.00   98
 59  \w     63.00  88.00   1.00    2.50    --  109.13 -70.00  -7.00   25
 60  \w   -130.00 -78.00   1.00    1.00    --  -42.05   0.00-180.00   52
 61  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00-120.00  176
 62  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00  30.00  176
 63  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00 -60.00  176
 64  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00 -30.00  176
 65  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00   0.00  176
 66  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00 -90.00  176
 67  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00  60.00  176
 68  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00  90.00  176
 69  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00 120.00  176
 70  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00 150.00  176
 71  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00-150.00  176
 72  \w    -46.00 130.00   1.00    1.00    --   42.05   0.00-180.00  176
;
_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      0.1327523000
_diffrn_orient_matrix_UB_12      0.0330126000
_diffrn_orient_matrix_UB_13      -0.0645215000
_diffrn_orient_matrix_UB_21      0.2113027000
_diffrn_orient_matrix_UB_22      -0.0789916000
_diffrn_orient_matrix_UB_23      0.0046030000
_diffrn_orient_matrix_UB_31      -0.1932876000
_diffrn_orient_matrix_UB_32      -0.0636968000
_diffrn_orient_matrix_UB_33      -0.0392443000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.1028
_diffrn_reflns_av_unetI/netI     0.0322
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -25
_diffrn_reflns_number            63297
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.995
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.399
_diffrn_reflns_theta_min         3.753
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.805
_exptl_absorpt_correction_T_max  0.993
_exptl_absorpt_correction_T_min  0.971
_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    1.427
_exptl_crystal_description       plate
_exptl_crystal_F_000             648
_exptl_crystal_size_max          0.313
_exptl_crystal_size_mid          0.178
_exptl_crystal_size_min          0.066
_refine_diff_density_max         0.428
_refine_diff_density_min         -0.297
_refine_diff_density_rms         0.059
_refine_ls_abs_structure_details
;
 Flack x determined using 1032 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.14(15)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.033
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     211
_refine_ls_number_reflns         2948
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.033
_refine_ls_R_factor_all          0.0538
_refine_ls_R_factor_gt           0.0477
_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^)+(0.0769P)^2^+0.6716P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1217
_refine_ls_wR_factor_ref         0.1282
_reflns_Friedel_coverage         0.680
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.989
_reflns_number_gt                2694
_reflns_number_total             2948
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7ob00006e2.cif
_cod_data_source_block           cs031
_cod_depositor_comments
'Adding full bibliography for 7155488--7155489.cif.'
_cod_database_code               7155488
_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              30297
_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 1.420
_oxdiff_exptl_absorpt_empirical_full_min 0.696