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_4514244
_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         'C22 H25 F N2 O3 S'
_chemical_formula_sum            'C22 H25 F N2 O3 S'
_chemical_formula_weight         416.50
_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            4
_cell_length_a                   8.25160(4)
_cell_length_b                   14.05983(9)
_cell_length_c                   17.50889(10)
_cell_measurement_reflns_used    22893
_cell_measurement_temperature    100
_cell_measurement_theta_max      75.5750
_cell_measurement_theta_min      4.0090
_cell_volume                     2031.31(2)
_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 0.998
_diffrn_measured_fraction_theta_max 0.995
_diffrn_measurement_details
;
  1 omega   37.00  117.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       44.0566   19.0000  -30.0000 80

  2 omega   83.00  109.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000   90.0000 26

  3 omega  119.00  178.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000   90.0000 59

  4 omega  150.00  176.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000    0.0000 26

  5 omega  122.00  178.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000  -30.0000 56

  6 omega  119.00  178.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000  -90.0000 59

  7 omega   83.00  163.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000   30.0000 80

  8 omega   84.00  120.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000    0.0000 36

  9 omega   83.00  112.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000   60.0000 29

 10 omega   78.00  104.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000  120.0000 26

 11 omega   83.00  112.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000  120.0000 29

 12 omega   83.00  177.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000  150.0000 94

 13 omega   78.00  104.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000    0.0000 26

 14 omega   83.00  141.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000  -30.0000 58

 15 omega   83.00  142.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000 -120.0000 59

 16 omega   83.00  109.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000 -150.0000 26

 17 omega   83.00  112.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000 -180.0000 29

 18 omega   78.00  171.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000 -120.0000 93

 19 omega   83.00  109.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000  -90.0000 26

 20 omega   83.00  112.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   61.0000  -60.0000 29

 21 omega   78.00  104.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000  -60.0000 26

 22 omega   78.00  104.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000  -30.0000 26

 23 omega   78.00  103.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000   30.0000 25

 24 omega   79.00  169.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000   60.0000 90

 25 omega   79.00  104.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000  150.0000 25

 26 omega   78.00  104.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000   90.0000 26

 27 omega   78.00  104.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000  -90.0000 26

 28 omega   78.00  104.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000 -150.0000 26

 29 omega   78.00  177.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049   77.0000 -180.0000 99

 30 omega   42.00  138.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049  -77.0000 -120.0000 96

 31 omega   61.00  121.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049 -125.0000   60.0000 60

 32 omega   31.00  107.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049  -95.0000   90.0000 76

 33 omega  -24.00   50.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       44.0566  -57.0000  -90.0000 74

 34 omega   29.00  108.00   1.0000    1.3250
omega____ theta____ kappa____ phi______ frames
    -      108.0049  -95.0000 -180.0000 79

 35 omega  -24.00   67.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       44.0566  -57.0000 -180.0000 91

 36 omega  -51.00  -20.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -57.0000 -150.0000 31

 37 omega  -78.00  -14.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000  -60.0000 64

 38 omega  -82.00  -14.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000   60.0000 68

 39 omega  -64.00  -14.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000  120.0000 50

 40 omega -115.00  -14.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000    0.0000 101

 41 omega -116.00  -15.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  -77.0000 -150.0000 101

 42 omega -130.00  -34.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -44.0566  178.0000  -60.0000 96
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Onyx, Ultra'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.1712086000
_diffrn_orient_matrix_UB_12      -0.0190390000
_diffrn_orient_matrix_UB_13      0.0315659000
_diffrn_orient_matrix_UB_21      -0.0738376000
_diffrn_orient_matrix_UB_22      0.0308510000
_diffrn_orient_matrix_UB_23      -0.0769012000
_diffrn_orient_matrix_UB_31      0.0095592000
_diffrn_orient_matrix_UB_32      -0.1034313000
_diffrn_orient_matrix_UB_33      -0.0287690000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0469
_diffrn_reflns_av_unetI/netI     0.0200
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            32280
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.991
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.726
_diffrn_reflns_theta_min         4.032
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'Enhance Ultra (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.717
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.70042
_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    1.362
_exptl_crystal_description       block
_exptl_crystal_F_000             880
_exptl_crystal_size_max          0.5
_exptl_crystal_size_mid          0.5
_exptl_crystal_size_min          0.3
_refine_diff_density_max         0.237
_refine_diff_density_min         -0.318
_refine_diff_density_rms         0.047
_refine_ls_abs_structure_details
;
 Flack x determined using 1717 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.000(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.059
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     264
_refine_ls_number_reflns         4185
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.059
_refine_ls_R_factor_all          0.0308
_refine_ls_R_factor_gt           0.0299
_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^)+(0.0505P)^2^+0.4308P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0772
_refine_ls_wR_factor_ref         0.0781
_reflns_Friedel_coverage         0.742
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.986
_reflns_number_gt                4087
_reflns_number_total             4185
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml7b00358_si_003.cif
_cod_data_source_block           38-135-fc-1-ss
_cod_depositor_comments
'Adding full bibliography for 4514240--4514245.cif.'
_cod_database_code               4514244
_shelxl_version_number           2013-4
_chemical_oxdiff_formula         C11H10N2O1
_reflns_odcompleteness_completeness 99.76
_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:
 C12(H12), C2(H2)
2.b Secondary CH2 refined with riding coordinates:
 C14(H14A,H14B), C13(H13A,H13B), C4(H4A,H4B), C15(H15A,H15B), C3(H3A,H3B)
2.c Aromatic/amide H refined with riding coordinates:
 C17(H17), C6(H6), C21(H21), C18(H18), C20(H20), C8(H8), C9(H9)
2.d Idealised Me refined as rotating group:
 C22(H22A,H22B,H22C), C1(H1A,H1B,H1C)
;
_shelx_res_checksum              87336
_shelx_hkl_checksum              8923
_olex2_date_sample_data_collection 2016-11-04
_olex2_exptl_crystal_mounting_method 'mounted on a Kyroloop using paratone oil'
_olex2_submission_special_instructions 'No special instructions were received'