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_4514240
_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 S'
_chemical_formula_sum            'C11 H10 Br2 F N S'
_chemical_formula_weight         367.08
_space_group_crystal_system      monoclinic
_space_group_IT_number           5
_space_group_name_Hall           'C 2y'
_space_group_name_H-M_alt        'C 1 2 1'
_symmetry_space_group_name_Hall  'C 2y'
_symmetry_space_group_name_H-M   'C 1 2 1'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2017-01-03
_audit_creation_method
;
Olex2 1.2
(compiled 2015.09.30 svn.r3233 for OlexSys, GUI svn.r5103)
;
_cell_angle_alpha                90
_cell_angle_beta                 95.8396(16)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   17.9328(3)
_cell_length_b                   6.97043(15)
_cell_length_c                   20.1733(3)
_cell_measurement_reflns_used    9851
_cell_measurement_temperature    100
_cell_measurement_theta_max      75.9160
_cell_measurement_theta_min      4.3460
_cell_volume                     2508.56(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 0.999
_diffrn_measured_fraction_theta_max 0.993
_diffrn_measurement_details
;
  1 omega    0.00   60.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -       44.1816  -38.0000  -90.0000 60

  2 omega   23.00   74.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -       44.1816   38.0000 -180.0000 51

  3 omega   20.00   46.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -       44.1816   57.0000  -90.0000 26

  4 omega   86.00  148.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  -90.0000 62

  5 omega  133.00  177.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  -60.0000 44

  6 omega  150.00  178.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000 -150.0000 28

  7 omega  131.00  174.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  -90.0000 43

  8 omega  102.00  174.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000  125.0000  -30.0000 72

  9 omega   85.00  113.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000 -180.0000 28

 10 omega   85.00  143.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000 -150.0000 58

 11 omega   84.00  123.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  -30.0000 39

 12 omega   85.00  169.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000   30.0000 84

 13 omega  117.00  178.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  150.0000 61

 14 omega   88.00  115.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   45.0000  150.0000 27

 15 omega   84.00  110.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000   90.0000 26

 16 omega   84.00  178.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000   60.0000 94

 17 omega   86.00  155.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000 -120.0000 69

 18 omega   84.00  135.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000    0.0000 51

 19 omega   81.00  108.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000   90.0000 27

 20 omega   85.00  175.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  120.0000 90

 21 omega   84.00  110.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  -60.0000 26

 22 omega   79.00  131.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  -30.0000 52

 23 omega   79.00  105.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000 -120.0000 26

 24 omega   80.00  107.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  -90.0000 27

 25 omega   79.00  106.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  -60.0000 27

 26 omega   80.00  107.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000    0.0000 27

 27 omega   80.00  105.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000   30.0000 25

 28 omega   79.00  106.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000   60.0000 27

 29 omega   80.00  106.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  150.0000 26

 30 omega   84.00  110.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  150.0000 26

 31 omega   28.00   97.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000  -30.0000 69

 32 omega   40.00  104.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000  -90.0000 64

 33 omega   38.00  123.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -       44.1816 -178.0000  -30.0000 85

 34 omega   37.00  121.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000 -125.0000   90.0000 84

 35 omega   28.00  109.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000  120.0000 81

 36 omega  -10.00   56.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -       44.1816  -38.0000   90.0000 66

 37 omega   79.00  105.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000 -150.0000 26

 38 omega   79.00  105.00   1.0000    8.7950
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000 -180.0000 26

 39 omega  -98.00  -14.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -      -44.1816  -77.0000 -150.0000 84

 40 omega -104.00  -14.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -      -44.1816  -77.0000   30.0000 90

 41 omega -113.00  -14.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -      -44.1816  -77.0000  -60.0000 99

 42 omega -116.00  -14.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -      -44.1816  -77.0000  120.0000 102

 43 omega -119.00  -34.00   1.0000    2.2000
omega____ theta____ kappa____ phi______ frames
    -      -44.1816  178.0000  -60.0000 85
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Onyx, Ultra'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      0.0762569000
_diffrn_orient_matrix_UB_12      -0.0257917000
_diffrn_orient_matrix_UB_13      0.0415283000
_diffrn_orient_matrix_UB_21      -0.0349952000
_diffrn_orient_matrix_UB_22      0.0649736000
_diffrn_orient_matrix_UB_23      0.0629597000
_diffrn_orient_matrix_UB_31      -0.0202316000
_diffrn_orient_matrix_UB_32      -0.2097122000
_diffrn_orient_matrix_UB_33      0.0144242000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0790
_diffrn_reflns_av_unetI/netI     0.0563
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       22
_diffrn_reflns_limit_h_min       -22
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -25
_diffrn_reflns_number            18765
_diffrn_reflns_point_group_measured_fraction_full 0.965
_diffrn_reflns_point_group_measured_fraction_max 0.946
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.147
_diffrn_reflns_theta_min         4.406
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'Enhance Ultra (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    9.643
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.31872
_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    1.944
_exptl_crystal_description       plate
_exptl_crystal_F_000             1424
_exptl_crystal_size_max          0.7
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.01
_refine_diff_density_max         1.432
_refine_diff_density_min         -0.973
_refine_diff_density_rms         0.175
_refine_ls_abs_structure_details
;
 Flack x determined using 1913 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.03(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.061
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     291
_refine_ls_number_reflns         4976
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.061
_refine_ls_R_factor_all          0.0610
_refine_ls_R_factor_gt           0.0575
_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^)+(0.1206P)^2^+2.0662P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1562
_refine_ls_wR_factor_ref         0.1617
_reflns_Friedel_coverage         0.755
_reflns_Friedel_fraction_full    0.925
_reflns_Friedel_fraction_max     0.891
_reflns_number_gt                4697
_reflns_number_total             4976
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml7b00358_si_006.cif
_cod_data_source_block           38-243
_cod_depositor_comments
'Adding full bibliography for 4514240--4514245.cif.'
_cod_original_cell_volume        2508.57(8)
_cod_database_code               4514240
_shelxl_version_number           2013-4
_chemical_oxdiff_formula         'C10 H10 N1 O1 S1 Br1'
_chemical_oxdiff_usercomment     DCM:Hexane
_reflns_odcompleteness_completeness 99.96
_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
2.a Ternary CH refined with riding coordinates:
 C13(H13), C2(H2)
2.b Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C15(H15A,H15B), C14(H14A,H14B), C4(H4A,H4B)
2.c Aromatic/amide H refined with riding coordinates:
 C20(H20), C9(H9), C11(H11), C22(H22)
2.d Idealised Me refined as rotating group:
 C12(H12A,H12B,H12C), C1(H1A,H1B,H1C)
;
_shelx_res_checksum              49411
_shelx_hkl_checksum              39624
_olex2_date_sample_data_collection 2016-12-31
_olex2_exptl_crystal_mounting_method 'Mounted on a Kryoloop using paratone oil'
_olex2_submission_special_instructions 'No special instructions were received'