Design, Synthesis, and Evaluation of a Series of Novel Super Long-Acting DPP-4 Inhibitors for the Treatment of Type 2 Diabetes.
Zhang, Chen; Ye, Fei; Wang, Jianmin; He, Ping; Lei, Ming; Huang, Longbin; Huang, Anbang; Tang, Pingming; Lin, Hongjun; Liao, Yuting; Liang, Yong; Ni, Jia; Yan, Pangke; Journal of medicinal chemistry  (2020) –; doi:10.1021/acs.jmedchem.0c00374

data_1558317
_publ_section_title
;
 Design, Synthesis, and Evaluation of a Series of Novel Super Long-Acting
 DPP-4 Inhibitors for the Treatment of Type 2 Diabetes.
;
_journal_name_full               'Journal of medicinal chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.0c00374
_journal_year                    2020
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C18 H20 F5 N4 O3 S, C2 F3 O2'
_chemical_formula_sum            'C20 H20 F8 N4 O5 S'
_chemical_formula_weight         580.46
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2016-03-31
_audit_creation_method
;
  Olex2 1.1
  (compiled 2011.02.15 svn.r1672, GUI svn.r3494)
;
_cell_angle_alpha                90.00
_cell_angle_beta                 94.623(2)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   6.12766(15)
_cell_length_b                   20.2470(5)
_cell_length_c                   10.0261(2)
_cell_measurement_reflns_used    4587
_cell_measurement_temperature    103.1
_cell_measurement_theta_max      70.8954
_cell_measurement_theta_min      4.3635
_cell_volume                     1239.86(5)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.35.11 (release 16-05-2011 CrysAlis171 .NET)
(compiled May 16 2011,17:55:39)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.35.11 (release 16-05-2011 CrysAlis171 .NET)
(compiled May 16 2011,17:55:39)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.35.11 (release 16-05-2011 CrysAlis171 .NET)
(compiled May 16 2011,17:55:39)
;
_computing_molecular_graphics
;
O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
OLEX2: a complete structure solution, refinement and analysis program.
J. Appl. Cryst. (2009). 42, 339-341.
;
_computing_publication_material
;
O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
OLEX2: a complete structure solution, refinement and analysis program.
J. Appl. Cryst. (2009). 42, 339-341.
;
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution
'A short history of SHELX (Sheldrick, 2007)/Bruker'
_diffrn_ambient_temperature      103.1
_diffrn_detector_area_resol_mean 16.0971
_diffrn_measured_fraction_theta_full 0.990
_diffrn_measured_fraction_theta_max 0.990
_diffrn_measurement_details
;
  1 omega  -36.00   -9.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       -8.5000  111.0000  -30.0000 27

  2 omega  -23.00   15.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       -8.5000  111.0000 -120.0000 38

  3 omega   65.00   94.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       36.7852   37.0000   90.0000 29

  4 omega  -26.00   43.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       36.7852  -77.0000 -180.0000 69

  5 omega   18.00  101.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       36.7852   77.0000  -60.0000 83

  6 omega   18.00  105.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       36.7852   37.0000 -120.0000 87

  7 omega  -31.00   61.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       36.7852  -77.0000   90.0000 92

  8 omega   54.00   79.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       36.7852   37.0000    0.0000 25

  9 omega  -27.00   39.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -       36.7852  -37.0000  -60.0000 66

 10 omega  145.00  174.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   77.0000  -60.0000 29

 11 omega   82.00  111.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   77.0000  -60.0000 29

 12 omega  127.00  169.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   77.0000  120.0000 42

 13 omega   42.00  130.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -77.0000  120.0000 88

 14 omega   82.00  175.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   76.0000 -129.0000 93

 15 omega   83.00  151.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   77.0000 -180.0000 68

 16 omega   70.00  117.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   15.0000  -30.0000 47

 17 omega   54.00   96.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -77.0000   60.0000 42

 18 omega   75.00  101.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   15.0000 -150.0000 26

 19 omega  142.00  173.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   77.0000  -30.0000 31

 20 omega   70.00  147.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   15.0000   30.0000 77

 21 omega   81.00  107.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   77.0000  -30.0000 26

 22 omega   85.00  164.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   77.0000    0.0000 79

 23 omega   81.00  176.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   77.0000  150.0000 95

 24 omega   62.00  115.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -15.0000   30.0000 53

 25 omega  102.00  178.00   1.0000    1.9000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  111.0000 -180.0000 76
;
_diffrn_measurement_device_type  'Xcalibur, Eos, Gemini'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.1198403000
_diffrn_orient_matrix_UB_12      -0.0615519000
_diffrn_orient_matrix_UB_13      -0.0592388000
_diffrn_orient_matrix_UB_21      0.0850871000
_diffrn_orient_matrix_UB_22      0.0149524000
_diffrn_orient_matrix_UB_23      -0.1373181000
_diffrn_orient_matrix_UB_31      0.2049376000
_diffrn_orient_matrix_UB_32      -0.0421393000
_diffrn_orient_matrix_UB_33      0.0376325000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.5418
_diffrn_reflns_av_R_equivalents  0.0313
_diffrn_reflns_av_unetI/netI     0.0451
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       24
_diffrn_reflns_limit_k_min       -24
_diffrn_reflns_limit_l_max       11
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            8355
_diffrn_reflns_theta_full        71.03
_diffrn_reflns_theta_max         71.03
_diffrn_reflns_theta_min         4.37
_diffrn_source                   'Enhance (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.093
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.65432
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.35.11 (release 16-05-2011 CrysAlis171 .NET)
(compiled May 16 2011,17:55:39)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.555
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       'not measured'
_exptl_crystal_F_000             592
_exptl_crystal_size_max          0.20
_exptl_crystal_size_mid          0.20
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.371
_refine_diff_density_min         -0.249
_refine_diff_density_rms         0.052
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.010(15)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.036
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     345
_refine_ls_number_reflns         4695
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.036
_refine_ls_R_factor_all          0.0377
_refine_ls_R_factor_gt           0.0364
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0578P)^2^+0.1823P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0942
_refine_ls_wR_factor_ref         0.0959
_reflns_number_gt                4557
_reflns_number_total             4695
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jm0c00374_si_001.cif
_cod_data_source_block           exp_3941
_cod_database_code               1558317
_reflns_odcompleteness_completeness 99.91
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97