Discovery of Novel Pyridone-Conjugated Monosulfactams as Potent and Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative Infections.
Tan, Liang; Tao, Yunliang; Wang, Ting; Zou, Feng; Zhang, Shuhua; Kou, Qunhuan; Niu, Ao; Chen, Qian; Chu, Wenjing; Chen, Xiaoyan; Wang, Haidong; Yang, Yushe; Journal of medicinal chemistry 60 (2017) 2669–2684; doi:10.1021/acs.jmedchem.6b01261

data_1545922
_publ_section_title
;
 Discovery of Novel Pyridone-Conjugated Monosulfactams as Potent and
 Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative
 Infections.
;
_journal_issue                   7
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              2669
_journal_page_last               2684
_journal_paper_doi               10.1021/acs.jmedchem.6b01261
_journal_volume                  60
_journal_year                    2017
_chemical_formula_moiety         'C35 H33 N O4, C2 H6 O'
_chemical_formula_sum            'C37 H39 N O5'
_chemical_formula_weight         577.69
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2016-05-20
_audit_creation_method
;
Olex2 1.2-beta
(compiled 2016.02.19 svn.r3266 for OlexSys, GUI svn.r5155)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.0661(8)
_cell_length_b                   10.4931(9)
_cell_length_c                   34.221(3)
_cell_measurement_reflns_used    9975
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      66.28
_cell_measurement_theta_min      2.58
_cell_volume                     3255.5(5)
_computing_cell_refinement       'SAINT v7.68A (Bruker, 2009)'
_computing_data_reduction        'SAINT v7.68A (Bruker, 2009)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 2008)'
_diffrn_ambient_temperature      298(2)
_diffrn_measured_fraction_theta_full 0.980
_diffrn_measured_fraction_theta_max 0.980
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0721
_diffrn_reflns_av_unetI/netI     0.0530
_diffrn_reflns_Laue_measured_fraction_full 0.980
_diffrn_reflns_Laue_measured_fraction_max 0.980
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       38
_diffrn_reflns_limit_l_min       -36
_diffrn_reflns_number            31207
_diffrn_reflns_point_group_measured_fraction_full 0.972
_diffrn_reflns_point_group_measured_fraction_max 0.972
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         67.703
_diffrn_reflns_theta_min         2.582
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.620
_exptl_absorpt_correction_T_max  0.7530
_exptl_absorpt_correction_T_min  0.4793
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2008/1 (Bruker,2008) was used for absorption correction.
wR2(int) was 0.1672 before and 0.0996 after correction.
The Ratio of minimum to maximum transmission is 0.6365.
The \l/2 correction factor is 0.0015.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.179
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             1232
_exptl_crystal_size_max          0.4
_exptl_crystal_size_mid          0.3
_exptl_crystal_size_min          0.25
_refine_diff_density_max         0.511
_refine_diff_density_min         -0.327
_refine_diff_density_rms         0.099
_refine_ls_abs_structure_details
;
 Flack x determined using 1871 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.00(12)
_refine_ls_extinction_coef       0.0009(8)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2014/7 (Sheldrick 2014'
_refine_ls_goodness_of_fit_ref   1.199
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     394
_refine_ls_number_reflns         5719
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.199
_refine_ls_R_factor_all          0.0990
_refine_ls_R_factor_gt           0.0937
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.2000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2667
_refine_ls_wR_factor_ref         0.2754
_reflns_Friedel_coverage         0.738
_reflns_Friedel_fraction_full    0.961
_reflns_Friedel_fraction_max     0.961
_reflns_number_gt                4999
_reflns_number_total             5719
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm6b01261_si_003.cif
_cod_data_source_block           cu_2016233_0m
_cod_database_code               1545922
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C24(H24), C11(H11), C7(H7), C8(H8)
2.b Secondary CH2 refined with riding coordinates:
 C2S(H2SA,H2SB)
2.c Aromatic/amide H refined with riding coordinates:
 C17(H17), C19(H19), C28(H28), C29(H29), C30(H30), C13(H13), C14(H14),
 C15(H15), C16(H16), C27(H27), C26(H26), C36(H36), C35(H35), C34(H34), C33(H33),
  C32(H32), C6(H6), C3(H3), C20(H20), C21(H21), C22(H22), C23(H23)
2.d Idealised Me refined as rotating group:
 C10(H10A,H10B,H10C), C9(H9A,H9B,H9C), C1S(H1SA,H1SB,H1SC)
2.e Idealised tetrahedral OH refined as rotating group:
 O4(H4), O12(H12)
;
_shelx_res_checksum              47059
_shelx_hkl_checksum              8376
_shelx_shelxl_version_number     2014/7
_olex2_submission_special_instructions 'No special instructions were received'