Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors.
Mahaney, Paige E.; Gavrin, Lori K.; Trybulski, Eugene J.; Stack, Gary P.; Vu, T. An; Cohn, Stephen T.; Ye, Fei; Belardi, Justin K.; Santilli, Arthur A.; Sabatucci, Joseph P.; Leiter, Jennifer; Johnston, Grace H.; Bray, Jenifer A.; Burroughs, Kevin D.; Cosmi, Scott A.; Leventhal, Liza; Koury, Elizabeth J.; Zhang, Yingru; Mugford, Cheryl A.; Ho, Douglas M.; Rosenzweig-Lipson, Sharon J; Platt, Brian; Smith, Valerie A.; Deecher, Darlene C.; Journal of medicinal chemistry 51 (2008) 4038–4049; doi:10.1021/jm8002262

data_1504346
_publ_section_title
;
 Structure-activity relationships of the cycloalkanol ethylamine scaffold:
 discovery of selective norepinephrine reuptake inhibitors.
;
_journal_issue                   13
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              4038
_journal_page_last               4049
_journal_paper_doi               10.1021/jm8002262
_journal_volume                  51
_journal_year                    2008
_chemical_absolute_configuration ad
_chemical_formula_iupac          '(C19 H31 Cl N2 O 2+) (Cl 1-)2'
_chemical_formula_moiety         'C19 H31 Cl N2 O 2+, 2(Cl 1-)'
_chemical_formula_structural     '(C19 H31 Cl N2 O) (Cl)2'
_chemical_formula_sum            'C19 H31 Cl3 N2 O'
_chemical_formula_weight         409.81
_chemical_name_common            'WAY-214,050-A-1  [ I-13233-115-2 ]'
_chemical_name_systematic
; 
 1-[(1R)-1-(3-Chlorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol
 Dihydrochloride
;
_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
_cell_angle_alpha                90.00
_cell_angle_beta                 94.469(1)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   10.3558(2)
_cell_length_b                   6.8232(1)
_cell_length_c                   14.7816(3)
_cell_measurement_reflns_used    28882
_cell_measurement_temperature    200(2)
_cell_measurement_theta_max      27.47
_cell_measurement_theta_min      1.38
_cell_volume                     1041.29(3)
_computing_cell_refinement       DENZO-SMN
_computing_data_collection       'Nonius COLLECT'
_computing_data_reduction        'DENZO-SMN, Siemens SHELXTL'
_computing_molecular_graphics    'Siemens SHELXTL'
_computing_publication_material  'Siemens SHELXTL'
_computing_structure_refinement  'Siemens SHELXTL'
_computing_structure_solution    'Siemens SHELXTL'
_diffrn_ambient_temperature      200(2)
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_diffrn_measurement_device       'Nonius KappaCCD'
_diffrn_measurement_method       '\w scans; 900 1.0\% rotations'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0899
_diffrn_reflns_av_sigmaI/netI    0.0536
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       0
_diffrn_reflns_number            28882
_diffrn_reflns_theta_full        27.47
_diffrn_reflns_theta_max         27.47
_diffrn_reflns_theta_min         1.38
_diffrn_standards_decay_%        0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.450
_exptl_absorpt_correction_T_max  0.99152
_exptl_absorpt_correction_T_min  0.93377
_exptl_absorpt_correction_type   gaussian
_exptl_crystal_colour            Colorless
_exptl_crystal_density_diffrn    1.307
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       Needle
_exptl_crystal_F_000             436
_exptl_crystal_size_max          0.18
_exptl_crystal_size_mid          0.10
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.211
_refine_diff_density_min         -0.199
_refine_diff_density_rms         0.048
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.07(6)
_refine_ls_extinction_coef       0.0083(11)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     SHELXL
_refine_ls_goodness_of_fit_all   1.079
_refine_ls_goodness_of_fit_obs   1.099
_refine_ls_hydrogen_treatment    refall
_refine_ls_matrix_type           full
_refine_ls_number_parameters     351
_refine_ls_number_reflns         4761
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.079
_refine_ls_restrained_S_obs      1.099
_refine_ls_R_factor_all          0.0665
_refine_ls_R_factor_obs          0.0484
_refine_ls_shift/esd_max         0.000
_refine_ls_shift/esd_mean        0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0120P)^2^+0.7355P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_all         0.0906
_refine_ls_wR_factor_obs         0.0832
_reflns_number_observed          3932
_reflns_number_total             4761
_reflns_observed_criterion       I&gt;2\s(I)
_cod_data_source_file            jm8002262-file004.cif
_cod_data_source_block
1-[(1R)-1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol
_cod_depositor_comments
;
The following automatic conversions were performed:

'_symmetry_cell_setting' value 'Monoclinic' changed to 'monoclinic'
according to /home/saulius/struct/CIF-dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.1 from 2010-06-29.

Automatic conversion script
Id: cif_fix_values 1715 2011-07-08 13:25:40Z adriana 
;
_cod_database_code               1504346