Synthesis and pharmacological evaluation of conformationally restricted κ-opioid receptor agonists
Wenker, Yvonne; Soeberdt, Michael; Daniliuc, Constantin; Ständer, Sonja; Schepmann, Dirk; Wünsch, Bernhard; Med. Chem. Commun. 7 (2016) 2368–; doi:10.1039/C6MD00441E

data_7119186
_publ_section_title
;
 Synthesis and pharmacological evaluation of conformationally restricted
 \k-opioid receptor agonists
;
_journal_issue                   12
_journal_name_full               'Med. Chem. Commun.'
_journal_page_first              2368
_journal_paper_doi               10.1039/C6MD00441E
_journal_volume                  7
_journal_year                    2016
_chemical_formula_sum            'C20 H27 Cl2 N3 O2'
_chemical_formula_weight         412.35
_space_group_IT_number           14
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  '-P 2ybc'
_symmetry_space_group_name_H-M   'P 1 21/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_audit_update_record
;
2016-06-14 deposited with the CCDC.
2016-09-22 downloaded from the CCDC.
;
_cell_angle_alpha                90.00
_cell_angle_beta                 105.364(8)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   14.181(2)
_cell_length_b                   12.8440(9)
_cell_length_c                   11.3534(8)
_cell_measurement_reflns_used    3421
_cell_measurement_temperature    223(2)
_cell_measurement_theta_max      68.25
_cell_measurement_theta_min      0.88
_cell_volume                     1994.0(4)
_computing_cell_refinement       'Collect (Nonius B.V., 1998)'
_computing_data_collection       'Collect (Nonius B.V., 1998)'
_computing_data_reduction        'Denzo-SMN (Otwinowski & Minor, 1997)'
_computing_molecular_graphics    'XP (BrukerAXS, 2000)'
_computing_publication_material  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      223(2)
_diffrn_measured_fraction_theta_full 0.972
_diffrn_measured_fraction_theta_max 0.972
_diffrn_measurement_device_type  'Nonius KappaCCD APEXII'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.038
_diffrn_reflns_av_sigmaI/netI    0.0228
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       0
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       0
_diffrn_reflns_number            16232
_diffrn_reflns_theta_full        66.90
_diffrn_reflns_theta_max         66.90
_diffrn_reflns_theta_min         4.72
_exptl_absorpt_coefficient_mu    3.094
_exptl_absorpt_correction_T_max  0.7473
_exptl_absorpt_correction_T_min  0.5118
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'Denzo (Otwinowski, Borek, Majewski & Minor, 2003)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.374
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             872
_exptl_crystal_size_max          0.25
_exptl_crystal_size_mid          0.20
_exptl_crystal_size_min          0.10
_refine_diff_density_max         0.175
_refine_diff_density_min         -0.255
_refine_diff_density_rms         0.036
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.040
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     245
_refine_ls_number_reflns         3445
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.040
_refine_ls_R_factor_all          0.0397
_refine_ls_R_factor_gt           0.0368
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0436P)^2^+0.9054P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0935
_refine_ls_wR_factor_ref         0.0959
_reflns_number_gt                3179
_reflns_number_total             3445
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            c6md00441e2.cif
_cod_data_source_block           fro6661
_cod_depositor_comments          'Adding full bibliography for 7119186.cif.'
_cod_original_cell_volume        1994.0(3)
_cod_original_sg_symbol_H-M      P21/c
_cod_database_code               7119186