Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopamine transporter.
Simoni, Daniele; Rossi, Marcello; Bertolasi, Valerio; Roberti, Marinella; Pizzirani, Daniela; Rondanin, Riccardo; Baruchello, Riccardo; Invidiata, Francesco Paolo; Tolomeo, Manlio; Grimaudo, Stefania; Merighi, Stefania; Varani, Katia; Gessi, Stefania; Borea, Pier Andrea; Marino, Silvia; Cavallini, Sabrina; Bianchi, Clementina; Siniscalchi, Anna; Journal of medicinal chemistry 48 (2005) 3337–3343; doi:10.1021/jm0490235

data_1506344
_publ_section_title
;
 Synthesis and pharmacology of 6-substituted benztropines: discovery of
 novel dopamine uptake inhibitors possessing low binding affinity to the
 dopamine transporter.
;
_journal_issue                   9
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              3337
_journal_page_last               3343
_journal_paper_doi               10.1021/jm0490235
_journal_volume                  48
_journal_year                    2005
_chemical_formula_moiety         'C19 H29 N O5'
_chemical_formula_sum            'C19 H29 N O5'
_chemical_formula_weight         351.43
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 97.132(2)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   6.866(1)
_cell_length_b                   19.559(1)
_cell_length_c                   7.040(1)
_cell_measurement_reflns_used    1457
_cell_measurement_temperature    295
_cell_measurement_theta_max      27.0
_cell_measurement_theta_min      4.5
_cell_volume                     938.1(2)
_computing_cell_refinement       'Denzo SMN (Otwinowski & Minor, 1997)'
_computing_data_collection       'COLLECT (Nonius, 1998)'
_computing_data_reduction        'Denzo SMN (Otwinowski & Minor, 1997)'
_computing_molecular_graphics    'ORTEP III (Burnett & Johnson, 1997)'
_computing_publication_material
;
SHELXL-97 (Sheldrick, 1997), PARST (Nardelli, 1995)
;
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SIR97 (Altomare et al., 1999)'
_diffrn_ambient_temperature      295
_diffrn_measured_fraction_theta_full 0.895
_diffrn_measured_fraction_theta_max 0.960
_diffrn_measurement_device_type  'Nonius Kappa CCD'
_diffrn_measurement_method       '\f scans and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71070
_diffrn_reflns_av_R_equivalents  0.055
_diffrn_reflns_av_sigmaI/netI    0.0599
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       24
_diffrn_reflns_limit_k_min       -20
_diffrn_reflns_limit_l_max       8
_diffrn_reflns_limit_l_min       -8
_diffrn_reflns_number            4997
_diffrn_reflns_theta_full        27.0
_diffrn_reflns_theta_max         27.0
_diffrn_reflns_theta_min         4.5
_exptl_absorpt_coefficient_mu    0.089
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.244
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       irregular
_exptl_crystal_F_000             380
_exptl_crystal_size_max          0.52
_exptl_crystal_size_mid          0.30
_exptl_crystal_size_min          0.27
_refine_diff_density_max         0.460
_refine_diff_density_min         -0.362
_refine_diff_density_rms         0.036
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.068
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     230
_refine_ls_number_reflns         2020
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.068
_refine_ls_R_factor_all          0.0910
_refine_ls_R_factor_gt           0.0677
_refine_ls_shift/su_max          0.005
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0778P)^2^+0.4184P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1719
_refine_ls_wR_factor_ref         0.1913
_reflns_number_gt                1415
_reflns_number_total             2020
_reflns_threshold_expression     I>2sigma(I)
_cod_data_source_file            jm0490235si20041201_050220.cif
_cod_data_source_block           (I)
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               1506344