Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors
Sonawane, Yogesh A.; Zhu, Yingmin; Garrison, Jered C.; Ezell, Edward L.; Zahid, Muhammad; Cheng, Xiaodong; Natarajan, Amarnath; ACS Medicinal Chemistry Letters 8 (2017) 1183–; doi:10.1021/acsmedchemlett.7b00358

data_4514241
_publ_section_title
;
 Structure--Activity Relationship Studies with Tetrahydroquinoline Analogs
 as EPAC Inhibitors
;
_journal_issue                   11
_journal_name_full               'ACS Medicinal Chemistry Letters'
_journal_page_first              1183
_journal_paper_doi               10.1021/acsmedchemlett.7b00358
_journal_volume                  8
_journal_year                    2017
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C11 H10 Br2 F N O'
_chemical_formula_sum            'C11 H10 Br2 F N O'
_chemical_formula_weight         351.02
_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             2016-11-14
_audit_creation_method
;
Olex2 1.2
(compiled 2015.09.30 svn.r3233 for OlexSys, GUI svn.r5103)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   9.35893(17)
_cell_length_b                   14.2993(3)
_cell_length_c                   17.3085(4)
_cell_measurement_reflns_used    10099
_cell_measurement_temperature    100
_cell_measurement_theta_max      76.0520
_cell_measurement_theta_min      5.1040
_cell_volume                     2316.33(8)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_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_temperature      100
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 8.2603
_diffrn_detector_type            Onyx
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.995
_diffrn_measurement_details
;
  1 omega  -24.00   66.00   1.0000   10.0000
omega____ theta____ kappa____ phi______ frames
    -       43.9628  -57.0000  -30.0000 90

  2 omega   65.00  110.00   1.0000   10.0000
omega____ theta____ kappa____ phi______ frames
    -       43.9628   57.0000  -90.0000 45

  3 omega  -20.00   72.00   1.0000   10.0000
omega____ theta____ kappa____ phi______ frames
    -       43.9628  -99.0000 -120.0000 92

  4 omega   20.00  112.00   1.0000   10.0000
omega____ theta____ kappa____ phi______ frames
    -       43.9628   57.0000  120.0000 92

  5 omega   35.00  105.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000   30.0000 70

  6 omega   40.00   74.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -45.0000 -180.0000 34

  7 omega   32.00   82.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000 -180.0000 50

  8 omega   87.00  120.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000 -125.0000 -180.0000 33

  9 omega   41.00   68.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -30.0000  -90.0000 27

 10 omega   44.00   72.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -45.0000   90.0000 28

 11 omega   36.00   66.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -30.0000   60.0000 30

 12 omega   29.00   99.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000   90.0000 70

 13 omega   49.00   76.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -45.0000  -60.0000 27

 14 omega   28.00   60.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000 -150.0000 32

 15 omega   42.00   71.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -45.0000 -150.0000 29

 16 omega   36.00   68.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -30.0000 -120.0000 32

 17 omega   66.00  107.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000 -150.0000 41

 18 omega   89.00  175.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000   45.0000   60.0000 86

 19 omega   44.00   69.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -30.0000   30.0000 25

 20 omega   46.00  107.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000  -60.0000 61

 21 omega   37.00  136.00   1.0000   40.0000
omega____ theta____ kappa____ phi______ frames
    -      109.0000    0.0000   60.0000 99
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Onyx, Ultra'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.1425822000
_diffrn_orient_matrix_UB_12      0.0511222000
_diffrn_orient_matrix_UB_13      -0.0140953000
_diffrn_orient_matrix_UB_21      -0.0637528000
_diffrn_orient_matrix_UB_22      -0.0470359000
_diffrn_orient_matrix_UB_23      0.0723181000
_diffrn_orient_matrix_UB_31      0.0517310000
_diffrn_orient_matrix_UB_32      0.0823640000
_diffrn_orient_matrix_UB_33      0.0499934000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.1152
_diffrn_reflns_av_unetI/netI     0.0688
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            17384
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.155
_diffrn_reflns_theta_min         4.010
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'Enhance Ultra (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    8.831
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.49671
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    2.013
_exptl_crystal_description       needle
_exptl_crystal_F_000             1360
_exptl_crystal_recrystallization_method 'crystalized from water and methanol'
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.05
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.571
_refine_diff_density_min         -0.865
_refine_diff_density_rms         0.151
_refine_ls_abs_structure_details
;
 Flack x determined using 1746 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.01(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.086
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     291
_refine_ls_number_reflns         4779
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.086
_refine_ls_R_factor_all          0.0531
_refine_ls_R_factor_gt           0.0500
_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^)+(0.0511P)^2^+8.3939P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1229
_refine_ls_wR_factor_ref         0.1244
_reflns_Friedel_coverage         0.751
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.979
_reflns_number_gt                4360
_reflns_number_total             4779
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml7b00358_si_005.cif
_cod_data_source_block           s-ce3f5_twin1_hklf4
_cod_depositor_comments
'Adding full bibliography for 4514240--4514245.cif.'
_cod_original_cell_volume        2316.32(8)
_cod_database_code               4514241
_shelxl_version_number           2013-4
_chemical_oxdiff_formula         C10H30N1O2
_chemical_oxdiff_usercomment     MeOH+Water
_diffrn_oxdiff_twin_integration_method simultaneous
_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
2.a Ternary CH refined with riding coordinates:
 C2(H2), C13(H13)
2.b Secondary CH2 refined with riding coordinates:
 C4(H4A,H4B), C3(H3A,H3B), C14(H14A,H14B), C15(H15A,H15B)
2.c Aromatic/amide H refined with riding coordinates:
 C11(H11), C20(H20), C9(H9), C22(H22)
2.d Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C), C12(H12A,H12B,H12C)
;
_shelx_res_checksum              15965
_shelx_hkl_checksum              16961
_olex2_exptl_crystal_mounting_method 'mounted on a Kyroloop in paratone oil'
_olex2_submission_special_instructions 'No special instructions were received'