Use of X-ray Co-crystal Structures and Molecular Modeling To Design Potent and Selective Non-peptide Inhibitors of Cathepsin K
Renee L. DesJarlais; Dennis S. Yamashita; Hye-Ja Oh; Irene N. Uzinskas; Karl F. Erhard; Andrew C. Allen; R. Curtis Haltiwanger; Baoguang Zhao; Ward W. Smith; Sherin S. Abdel-Meguid; Karla D'Alessio; Cheryl A. Janson; Michael S. McQueney; Thaddeus A. Tomaszek; Mark A. Levy; Daniel F. Veber; Journal of the American Chemical Society 120 (1998) 9114–9115; doi:10.1021/ja981171v

data_4116830
_publ_section_title
;
 Use of X-ray Co-crystal Structures and Molecular Modeling To Design
 Potent and Selective Non-peptide Inhibitors of Cathepsin K
;
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              9114
_journal_page_last               9115
_journal_paper_doi               10.1021/ja981171v
_journal_volume                  120
_journal_year                    1998
_chemical_formula_sum            'C26 H30 Br N O2'
_chemical_formula_weight         468.42
_chemical_name_common
;
p-bromophenethylene salt of 2-(3-biphenyl)-4-methyl-valeric acid
;
_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                 113.41(7)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   14.337(7)
_cell_length_b                   6.477(3)
_cell_length_c                   14.386(6)
_cell_measurement_temperature    293(2)
_cell_volume                     1225.9(12)
_computing_cell_refinement       MADNES
_computing_data_collection       MADNES
_computing_data_reduction        MADNES
_computing_molecular_graphics    'SHELXTL - XP'
_computing_publication_material  'SHELXTL - CIFTAB'
_computing_structure_refinement  'SHELXTL - XL'
_computing_structure_solution    'SHELXTL - XS'
_diffrn_ambient_temperature      293(2)
_diffrn_measurement_device       'Enraf Nonius FAST Area detector'
_diffrn_measurement_method       '0.2 degree increments in phi'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'rotating anode'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.1081
_diffrn_reflns_av_sigmaI/netI    0.0747
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            8964
_diffrn_reflns_theta_max         22.70
_diffrn_reflns_theta_min         2.58
_exptl_absorpt_coefficient_mu    1.697
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            'clear colorless'
_exptl_crystal_density_diffrn    1.269
_exptl_crystal_description       needles
_exptl_crystal_F_000             488
_exptl_crystal_size_max          0.80
_exptl_crystal_size_mid          0.06
_exptl_crystal_size_min          0.04
_refine_diff_density_max         0.700
_refine_diff_density_min         -0.570
_refine_diff_density_rms         0.082
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.02(2)
_refine_ls_extinction_coef       0.0506(46)
_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   1.077
_refine_ls_goodness_of_fit_obs   1.062
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     284
_refine_ls_number_reflns         3171
_refine_ls_number_restraints     10
_refine_ls_restrained_S_all      1.078
_refine_ls_restrained_S_obs      1.059
_refine_ls_R_factor_all          0.0799
_refine_ls_R_factor_obs          0.0641
_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^)+(0.0553P)^2^+2.7238P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_all         0.1606
_refine_ls_wR_factor_obs         0.1436
_reflns_number_observed          2662
_reflns_number_total             3172
_reflns_observed_criterion       >2sigma(I)
_cod_data_source_file            ja981171v.cif
_cod_data_source_block           x1671a1
_cod_depositor_comments
;
The following automatic conversions were performed:

'_refine_ls_weighting_scheme' value 'calc
w=1/[\s^2^(Fo^2^)+(0.0553P)^2^+2.7238P] where P=(Fo^2^+2Fc^2^)/3' was
changed to 'calc'. New tag '_refine_ls_weighting_details' was
created. The value of the new tag was set to
'w=1/[\s^2^(Fo^2^)+(0.0553P)^2^+2.7238P] where P=(Fo^2^+2Fc^2^)/3'.

Automatic conversion script
Id: cif_fix_values 3143 2015-03-26 13:38:13Z robertas 
;
_cod_original_cell_volume        1225.9(10)
_cod_database_code               4116830