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_4514245
_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                   9.36317(8)
_cell_length_b                   14.30780(11)
_cell_length_c                   17.31825(12)
_cell_measurement_reflns_used    26301
_cell_measurement_temperature    100
_cell_measurement_theta_max      76.0460
_cell_measurement_theta_min      5.0870
_cell_volume                     2320.06(3)
_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 0.998
_diffrn_measurement_details
;
  1 omega -116.00  -14.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000 -180.0000 102

  2 omega -116.00  -14.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000    0.0000 102

  3 omega -112.00  -20.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -57.0000   30.0000 92

  4 omega -112.00  -20.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -57.0000 -180.0000 92

  5 omega -116.00  -14.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000   90.0000 102

  6 omega -116.00  -14.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000  -90.0000 102

  7 omega -130.00  -34.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  178.0000  -90.0000 96

  8 omega   21.00  115.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       44.0566   38.0000  -90.0000 94

  9 omega  -25.00   68.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       44.0566  -57.0000  120.0000 93

 10 omega  -25.00   68.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       44.0566  -57.0000 -120.0000 93

 11 omega   84.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  -90.0000 94

 12 omega   79.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  150.0000 99

 13 omega   28.00  109.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000   60.0000 81

 14 omega   84.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000 -120.0000 94

 15 omega   79.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  -90.0000 99

 16 omega   32.00  113.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000 -105.0000  -71.0000 81

 17 omega   28.00  109.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000  -30.0000 81

 18 omega   84.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000 -150.0000 94

 19 omega   79.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000   60.0000 99

 20 omega   79.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  120.0000 99

 21 omega   79.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000    0.0000 99

 22 omega   79.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  -60.0000 99

 23 omega   79.00  105.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000   90.0000 26

 24 omega   84.00  112.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  150.0000 28

 25 omega   85.00  113.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000   30.0000 28

 26 omega   84.00  175.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  -60.0000 91

 27 omega   84.00  113.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000 -180.0000 29

 28 omega   85.00  160.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000   60.0000 75

 29 omega  120.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000 -120.0000 58

 30 omega   80.00  105.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000 -120.0000 25

 31 omega   84.00  111.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  120.0000 27

 32 omega   84.00  111.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000    0.0000 27

 33 omega   50.00  105.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000 -180.0000 55

 34 omega   79.00  113.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000 -180.0000 34

 35 omega   80.00  107.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000   30.0000 27

 36 omega   84.00  135.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000  -30.0000 51

 37 omega   79.00  178.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000  -30.0000 99

 38 omega   84.00  173.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   61.0000   90.0000 89

 39 omega   79.00  176.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000   77.0000 -150.0000 97

 40 omega   29.00   90.00   1.0000    3.7700
omega____ theta____ kappa____ phi______ frames
    -      109.0000  -95.0000  150.0000 61
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Onyx, Ultra'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.0052072000
_diffrn_orient_matrix_UB_12      0.0477056000
_diffrn_orient_matrix_UB_13      -0.0797270000
_diffrn_orient_matrix_UB_21      -0.1040232000
_diffrn_orient_matrix_UB_22      0.0738010000
_diffrn_orient_matrix_UB_23      0.0321703000
_diffrn_orient_matrix_UB_31      0.1272466000
_diffrn_orient_matrix_UB_32      0.0622584000
_diffrn_orient_matrix_UB_33      0.0229724000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0757
_diffrn_reflns_av_unetI/netI     0.0282
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            48567
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.997
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.288
_diffrn_reflns_theta_min         4.008
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'Enhance Ultra (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    8.817
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.20912
_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 light orange'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    orange
_exptl_crystal_density_diffrn    2.010
_exptl_crystal_description       needle
_exptl_crystal_F_000             1360
_exptl_crystal_recrystallization_method 'grown from methanol'
_exptl_crystal_size_max          0.5
_exptl_crystal_size_mid          0.05
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.551
_refine_diff_density_min         -0.570
_refine_diff_density_rms         0.112
_refine_ls_abs_structure_details
;
 Flack x determined using 1938 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.029(11)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.045
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     291
_refine_ls_number_reflns         4840
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.045
_refine_ls_R_factor_all          0.0330
_refine_ls_R_factor_gt           0.0310
_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^)+(0.0552P)^2^+2.1658P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0830
_refine_ls_wR_factor_ref         0.0851
_reflns_Friedel_coverage         0.761
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.995
_reflns_number_gt                4589
_reflns_number_total             4840
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml7b00358_si_004.cif
_cod_data_source_block           r-ce3f5
_cod_depositor_comments
'Adding full bibliography for 4514240--4514245.cif.'
_cod_database_code               4514245
_shelxl_version_number           2013-4
_chemical_oxdiff_formula         C10H11N1O2
_chemical_oxdiff_usercomment     MeOH
_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:
 C15(H15A,H15B), C14(H14A,H14B), C3(H3A,H3B), C4(H4A,H4B)
2.c Aromatic/amide H refined with riding coordinates:
 C22(H22), C9(H9), C20(H20), C11(H11)
2.d Idealised Me refined as rotating group:
 C12(H12A,H12B,H12C), C1(H1A,H1B,H1C)
;
_shelx_res_checksum              14399
_shelx_hkl_checksum              8283
_olex2_date_sample_data_collection 2016-11-02
_olex2_exptl_crystal_mounting_method 'mounted on Kryoloop using paratone oil'
_olex2_submission_special_instructions 'No special instructions were received'