Second-generation antibacterial benzimidazole ureas: discovery of a preclinical candidate with reduced metabolic liability.
Grillot, Anne-Laure; Le Tiran, Arnaud; Shannon, Dean; Krueger, Elaine; Liao, Yusheng; O'Dowd, Hardwin; Tang, Qing; Ronkin, Steve; Wang, Tiansheng; Waal, Nathan; Li, Pan; Lauffer, David; Sizensky, Emmanuelle; Tanoury, Jerry; Perola, Emanuele; Grossman, Trudy H.; Doyle, Tim; Hanzelka, Brian; Jones, Steven; Dixit, Vaishali; Ewing, Nigel; Liao, Shengkai; Boucher, Brian; Jacobs, Marc; Bennani, Youssef; Charifson, Paul S.; Journal of medicinal chemistry 57 (2014) 8792–8816; doi:10.1021/jm500563g

data_1518125
_publ_section_title
;
 Second-generation antibacterial benzimidazole ureas: discovery of a
 preclinical candidate with reduced metabolic liability.
;
_journal_issue                   21
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              8792
_journal_page_last               8816
_journal_paper_doi               10.1021/jm500563g
_journal_volume                  57
_journal_year                    2014
_chemical_formula_sum            'C21 H25 F N6 O3'
_chemical_formula_weight         428.47
_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
_audit_update_record
;
2010-12-17 # Formatted by publCIF
;
_cell_angle_alpha                90.00
_cell_angle_beta                 102.8260(10)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   9.9016(2)
_cell_length_b                   10.9184(2)
_cell_length_c                   19.2975(4)
_cell_measurement_reflns_used    6639
_cell_measurement_temperature    100(2)
_cell_volume                     2034.19(7)
_computing_cell_refinement       'Apex II'
_computing_data_collection       'Apex II'
_computing_data_reduction        'Apex II'
_computing_molecular_graphics    Mercury
_computing_publication_material  publCIF
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.986
_diffrn_measured_fraction_theta_max 0.986
_diffrn_measurement_device_type  'APEX II'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0224
_diffrn_reflns_av_sigmaI/netI    0.0275
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            14666
_diffrn_reflns_theta_full        64.88
_diffrn_reflns_theta_max         64.88
_diffrn_reflns_theta_min         2.35
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.856
_exptl_absorpt_correction_T_max  0.9193
_exptl_absorpt_correction_T_min  0.8824
_exptl_crystal_density_diffrn    1.399
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             904
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.10
_refine_diff_density_max         0.183
_refine_diff_density_min         -0.186
_refine_diff_density_rms         0.035
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.08(12)
_refine_ls_extinction_coef       0.00020(15)
_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_ref   1.021
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     731
_refine_ls_number_reflns         6639
_refine_ls_number_restraints     33
_refine_ls_restrained_S_all      1.018
_refine_ls_R_factor_all          0.0371
_refine_ls_R_factor_gt           0.0338
_refine_ls_shift/su_max          3.400
_refine_ls_shift/su_mean         0.007
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0546P)^2^+0.3977P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0851
_refine_ls_wR_factor_ref         0.0871
_reflns_number_gt                6210
_reflns_number_total             6639
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jm500563g_si_002.cif
_cod_data_source_block           vrt-928486
_cod_depositor_comments          'Adding full bibliography for 1518125.cif.'
_cod_database_code               1518125