Discovery of WAY-260022, a Potent and Selective Inhibitor of the Norepinephrine Transporter
Gavrin, Lori K.; Mahaney, Paige E.; Jenkins, Douglas; Nogle, Lisa M.; Mugford, Cheryl A.; Huselton, Christine; Leiter, Jennifer; Johnston, Grace H.; Bray, Jenifer A.; Burroughs, Kevin D.; Cosmi, Scott A.; Alfinito, Peter; Ho, Douglas M.; Deecher, Darlene C.; Trybulski, Eugene J.; ACS Medicinal Chemistry Letters 1 (2010) 91–; doi:10.1021/ml100009p

data_4510954
_publ_section_title
;
 Discovery of WAY-260022, a Potent and Selective Inhibitor of the
 Norepinephrine Transporter
;
_journal_issue                   3
_journal_name_full               'ACS Medicinal Chemistry Letters'
_journal_page_first              91
_journal_paper_doi               10.1021/ml100009p
_journal_volume                  1
_journal_year                    2010
_chemical_absolute_configuration ad
_chemical_compound_source        'chemical synthesis'
_chemical_formula_iupac          '(C21 H33 F3 N2 O2) (Cl)2'
_chemical_formula_moiety         'C21 H33 F3 N2 O2 2+, 2(Cl 1-)'
_chemical_formula_structural     '(C21 H33 F3 N2 O2) (Cl)2'
_chemical_formula_sum            'C21 H33 Cl2 F3 N2 O2'
_chemical_formula_weight         473.39
_chemical_melting_point          '262-264\%C (dec)'
_chemical_name_common            'Wyeth WAY-260022-A-6  [L31097-45-A]'
_chemical_name_systematic
;
1-{(1<i>S</i>)-2-[(<i>cis</i>)-3,5-Dimethylpiperazin-l-yl]-1-
[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol Dihydrochloride
;
_space_group_IT_number           19
_symmetry_cell_setting           orthorhombic
_symmetry_Int_Tables_number      19
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_cell_angle_alpha                90.00
_cell_angle_beta                 90.00
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   6.60120(10)
_cell_length_b                   11.6826(3)
_cell_length_c                   29.9592(7)
_cell_measurement_reflns_used    34587
_cell_measurement_temperature    200(2)
_cell_measurement_theta_max      27.50
_cell_measurement_theta_min      1.36
_cell_volume                     2310.43(9)
_computing_cell_refinement       'DENZO-SMN (Otwinowski & Minor, 1997)'
_computing_data_collection       'COLLECT (Nonius, 1998)'
_computing_data_reduction
;
DENZO-SMN (Otwinowski & Minor, 1997), SHELXTL v2008/4 (Sheldrick, 1996)
;
_computing_molecular_graphics    'SHELXTL v2008/4 (Sheldrick, 2008)'
_computing_publication_material  'SHELXTL v2008/4 (Sheldrick, 2008)'
_computing_structure_refinement  'SHELXTL v2008/4 (Sheldrick, 2008)'
_computing_structure_solution    'SHELXTL v2008/4 (Sheldrick, 2008)'
_diffrn_ambient_temperature      200(2)
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device       'Nonius KappaCCD'
_diffrn_measurement_method       '\w scans; 800 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  0.1055
_diffrn_reflns_av_sigmaI/netI    0.0439
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       38
_diffrn_reflns_limit_l_min       -38
_diffrn_reflns_number            34587
_diffrn_reflns_theta_full        27.50
_diffrn_reflns_theta_max         27.50
_diffrn_reflns_theta_min         1.36
_diffrn_standards_decay_%        0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.325
_exptl_absorpt_correction_T_max  0.9760
_exptl_absorpt_correction_T_min  0.9232
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details   'SHELXTL v2008/4 (Sheldrick, 2008)'
_exptl_crystal_colour            Colorless
_exptl_crystal_density_diffrn    1.361
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       Needle
_exptl_crystal_F_000             1000
_exptl_crystal_recrystallization_method
;
Slow evaporation of a methanol solution of WAY-260022-A-6.
;
_exptl_crystal_size_max          0.250
_exptl_crystal_size_mid          0.125
_exptl_crystal_size_min          0.075
_refine_diff_density_max         0.212
_refine_diff_density_min         -0.205
_refine_diff_density_rms         0.046
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.04(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.033
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     285
_refine_ls_number_reflns         5311
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.033
_refine_ls_R_factor_all          0.0562
_refine_ls_R_factor_gt           0.0411
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0322P)^2^+0.8900P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0829
_refine_ls_wR_factor_ref         0.0892
_reflns_number_gt                4477
_reflns_number_total             5311
_reflns_threshold_expression     I>2\s(I)
_cod_data_source_file            ml100009p_si_003.cif
_cod_data_source_block           WAY-260022-A-6
_cod_depositor_comments
;
The following automatic conversions were performed:

'_symmetry_cell_setting' value 'Orthorhombic' changed to
'orthorhombic' according to
/usr/data/users/saulius/automatic-downloads/retrospective/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 from 2011-04-26.

Automatic conversion script
Id: cif_fix_values 2281 2013-09-26 08:29:07Z andrius 
;
_cod_database_code               4510954