Rational design of 5-HT6R ligands using a bioisosteric strategy: Synthesis, biological evaluation and molecular modelling
Staroń, Jakub; Warszycki, Dawid; Kalinowska-Tłuścik, Justyna; Satała, Grzegorz; Bojarski, AJ; RSC Adv.  (2015) –; doi:10.1039/C5RA00054H

data_7219751
_publ_section_title
;
 Rational design of 5-HT6R ligands using a bioisosteric strategy:
 Synthesis, biological evaluation and molecular modelling
;
_journal_name_full               'RSC Adv.'
_journal_paper_doi               10.1039/C5RA00054H
_journal_year                    2015
_chemical_formula_moiety         'C19 H22 N4 O2'
_chemical_formula_sum            'C19 H22 N4 O2'
_chemical_formula_weight         338.4
_chemical_name_common            'Compound 180'
_chemical_name_systematic
;
2-[5-(4-methylpiperazin-1-yl)-2-nitrophenyl]-2,3-dihydro-1H-isoindole
;
_space_group_IT_number           14
_symmetry_cell_setting           monoclinic
_symmetry_Int_Tables_number      14
_symmetry_space_group_name_Hall  '-P 2ybc'
_symmetry_space_group_name_H-M   'P 1 21/c 1'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2014-02-04T22:15:55-00:00
_audit_creation_method           'WinGX routine CIF_UPDATE'
_audit_update_record
;
2014-04-05 deposited with the CCDC.
2015-03-04 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 128.998(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.2516(3)
_cell_length_b                   18.4177(5)
_cell_length_c                   12.6426(3)
_cell_measurement_reflns_used    4143
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      27.485
_cell_measurement_theta_min      0.998
_cell_volume                     1674.19(9)
_computing_cell_refinement       'HKL Scalepack (Otwinowski & Minor 1997)'
_computing_data_collection       'Collect (Bruker AXS BV, 1997-2004)'
_computing_data_reduction
'HKL Denzo and Scalepack (Otwinowski & Minor 1997)'
_computing_structure_refinement  'SHELXL-2013 (Sheldrick, 2013)'
_diffrn_ambient_temperature      100(2)
_diffrn_detector_area_resol_mean 9
_diffrn_measured_fraction_theta_full 0.995
_diffrn_measured_fraction_theta_max 0.993
_diffrn_measurement_device       '95mm CCD camera on \k-goniostat'
_diffrn_measurement_device_type  KappaCCD
_diffrn_measurement_method       CCD
_diffrn_orient_matrix_type       'by Bruker AXS Collect from scalepack cell'
_diffrn_orient_matrix_UB_11      -0.0880136
_diffrn_orient_matrix_UB_12      0.0005177
_diffrn_orient_matrix_UB_13      -0.07028
_diffrn_orient_matrix_UB_21      0.0374164
_diffrn_orient_matrix_UB_22      -0.0437593
_diffrn_orient_matrix_UB_23      -0.0441117
_diffrn_orient_matrix_UB_31      -0.0523455
_diffrn_orient_matrix_UB_32      -0.0321382
_diffrn_orient_matrix_UB_33      0.0589294
_diffrn_radiation_monochromator  'horizonally mounted graphite crystal'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0185
_diffrn_reflns_Laue_measured_fraction_full 0.995
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       23
_diffrn_reflns_limit_k_min       -21
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            9948
_diffrn_reflns_point_group_measured_fraction_full 0.995
_diffrn_reflns_point_group_measured_fraction_max 0.993
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.501
_diffrn_reflns_theta_min         2.349
_exptl_absorpt_coefficient_mu    0.09
_exptl_absorpt_correction_T_max  0.982
_exptl_absorpt_correction_T_min  0.957
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
        DENZO-SMN; Otwinowski & Minor, 1997
;
_exptl_crystal_colour            orange
_exptl_crystal_density_diffrn    1.343
_exptl_crystal_description       prism
_exptl_crystal_F_000             720
_exptl_crystal_size_max          0.5
_exptl_crystal_size_mid          0.4
_exptl_crystal_size_min          0.2
_refine_diff_density_max         0.321
_refine_diff_density_min         -0.268
_refine_diff_density_rms         0.047
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.038
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     226
_refine_ls_number_reflns         3819
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.038
_refine_ls_R_factor_all          0.0444
_refine_ls_R_factor_gt           0.0378
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0470P)^2^+0.6953P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0949
_refine_ls_wR_factor_ref         0.0993
_reflns_number_gt                3355
_reflns_number_total             3819
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c5ra00054h2.cif
_cod_data_source_block           new
_cod_original_cell_volume        1674.18(9)
_cod_original_sg_symbol_H-M      'P 21/c'
_cod_database_code               7219751