Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues.
Yoon, Ji-Seong; Kim, Gyudong; Jarhad, Dnyandev B.; Kim, Hong-Rae; Shin, Young-Sup; Qu, Shuhao; Sahu, Pramod K.; Kim, Hea Ok; Lee, Hyuk Woo; Wang, Su Bin; Kong, Yun Jeong; Chang, Tong-Shin; Ogando, Natacha S.; Kovacikova, Kristina; Snijder, Eric J.; Posthuma, Clara C.; van Hemert, Martijn J.; Jeong, Lak Shin; Journal of medicinal chemistry 62 (2019) 6346–6362; doi:10.1021/acs.jmedchem.9b00781

data_1552561
_publ_section_title
;
 Design, Synthesis, and Anti-RNA Virus Activity of
 6'-Fluorinated-Aristeromycin Analogues.
;
_journal_issue                   13
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              6346
_journal_page_last               6362
_journal_paper_doi               10.1021/acs.jmedchem.9b00781
_journal_volume                  62
_journal_year                    2019
_chemical_absolute_configuration unk
_chemical_formula_moiety         'C11 H13 F2 N5 O3, 1.5(H2 O)'
_chemical_formula_sum            'C11 H16 F2 N5 O4.5'
_chemical_formula_weight         328.29
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2017-01-25
_audit_creation_method
;
Olex2 1.2
(compiled 2017.01.04 svn.r3372 for OlexSys, GUI svn.r5292)
;
_cell_angle_alpha                90
_cell_angle_beta                 96.8278(7)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.20373(8)
_cell_length_b                   6.97368(6)
_cell_length_c                   18.69692(15)
_cell_measurement_reflns_used    16832
_cell_measurement_temperature    99.9(5)
_cell_measurement_theta_max      76.3640
_cell_measurement_theta_min      2.3640
_cell_volume                     1320.992(19)
_computing_cell_refinement       'CrysAlisPro 1.171.38.44a (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.44a (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.44a (Rigaku OD, 2015)'
_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    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.9(5)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.2262
_diffrn_detector_type            AtlasS2
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
--------------------------------------------------------------------------
  1  \w   -112.00 -36.00   1.00    1.00    --  -41.24 -57.00 -60.00   76
  2  \w     24.00  92.00   1.00    1.00    --   41.24-125.00 150.00   68
  3  \w      3.00  40.00   1.00    1.00    --   41.24 -99.00  30.00   37
  4  \w     33.00  87.00   1.00    1.00    --   41.24-125.00 -30.00   54
  5  \w    153.00 178.00   1.00    2.32    --  112.00  77.00-120.00   25
  6  \w     89.00 119.00   1.00    2.32    --  112.00  61.00 -90.00   30
  7  \w    102.00 175.00   1.00    2.32    --  112.00  45.00  30.00   73
  8  \w    113.00 142.00   1.00    2.32    --  112.00 -77.00 120.00   29
  9  \w    113.00 140.00   1.00    2.32    --  112.00  77.00-120.00   27
 10  \w     37.00 112.00   1.00    2.32    --  112.00 -77.00 120.00   75
 11  \w     86.00 111.00   1.00    2.32    --  112.00  61.00 -30.00   25
 12  \w    120.00 168.00   1.00    2.32    --  112.00  61.00 -30.00   48
 13  \w     84.00 122.00   1.00    2.32    --  112.00  61.00   0.00   38
 14  \w    125.00 154.00   1.00    2.32    --  112.00  61.00 -90.00   29
 15  \w    134.00 178.00   1.00    2.32    --  112.00 111.00 -30.00   44
 16  \w     84.00 111.00   1.00    2.32    --  112.00  77.00-120.00   27
 17  \w    129.00 178.00   1.00    2.32    --  112.00  61.00   0.00   49
 18  \w     39.00  66.00   1.00    2.32    --  112.00 -94.00-180.00   27
 19  \w     36.00  96.00   1.00    2.32    --  112.00-111.00 120.00   60
 20  \w      1.00  26.00   1.00    1.00    --   38.00  90.00  72.70   25
 21  \w    -47.00 -17.00   1.00    1.00    --  -41.24 -38.00-150.00   30
 22  \w   -115.00 -48.00   1.00    1.00    --  -41.24 -38.00-150.00   67
 23  \w    -62.00  26.00   1.00    1.00    --  -41.24  38.00 -90.00   88
 24  \w   -113.00 -17.00   1.00    1.00    --  -41.24 -57.00  90.00   96
 25  \w      8.00  33.00   1.00    1.00    --   42.00  81.00 -93.69   25
 26  \w     16.00  42.00   1.00    1.00    --   50.00  81.00 166.04   26
 27  \w     21.00  46.00   1.00    1.00    --   54.00  78.00  55.82   25
 28  \w     21.00  47.00   1.00    1.00    --   54.00  78.00-103.88   26
 29  \w     21.00  47.00   1.00    1.00    --   54.00  79.00 -50.91   26
 30  \w     21.00  46.00   1.00    1.00    --   54.00  79.00-139.45   25
 31  \w     30.00  58.00   1.00    1.00    --   58.00  77.00 103.26   28
 32  \w     84.00 133.00   1.00    1.00    --   58.00  77.00 103.26   49
 33  \w     33.00  69.00   1.00    1.00    --   62.00  77.00 -20.27   36
 34  \w     31.00  78.00   1.00    1.00    --   62.00  76.00  67.30   47
 35  \w     31.00  57.00   1.00    1.00    --   62.00  76.00 147.06   26
 36  \w     83.00 112.00   1.00    1.00    --   66.00  77.00 167.90   29
 37  \w     34.00  67.00   1.00    1.00    --   66.00  76.00-132.98   33
 38  \w     34.00  71.00   1.00    1.00    --   66.00  77.00 167.90   37
 39  \w    107.00 140.00   1.00    1.00    --   66.00  76.00-132.98   33
 40  \w     34.00  71.00   1.00    1.00    --   66.00  75.00  31.24   37
 41  \w    102.00 146.00   1.00    1.00    --   70.00  76.00 -56.63   44
 42  \w     38.00  80.00   1.00    1.00    --   70.00  76.00 -56.63   42
 43  \w     38.00  64.00   1.00    1.00    --   70.00  76.00 -86.65   26
 44  \w    121.00 176.00   1.00    2.32    --  112.00 111.00 150.00   55
 45  \w     54.00  81.00   1.00    2.32    --  112.00-111.00 -90.00   27
 46  \w     81.00 117.00   1.00    2.32    --  112.00  77.00 -30.00   36
 47  \w     79.00 105.00   1.00    2.32    --  112.00  77.00-120.00   26
 48  \w     79.00 114.00   1.00    2.32    --  112.00  77.00 -60.00   35
 49  \w    115.00 172.00   1.00    2.32    --  112.00  77.00 -60.00   57
 50  \w     58.00  85.00   1.00    2.32    --  112.00 -94.00   0.00   27
 51  \w     79.00 105.00   1.00    2.32    --  112.00  77.00-180.00   26
 52  \w    132.00 177.00   1.00    2.32    --  112.00  77.00  30.00   45
 53  \w     80.00 105.00   1.00    2.32    --  112.00  77.00  30.00   25
 54  \w     83.00 110.00   1.00    2.32    --  112.00  61.00  30.00   27
 55  \w     83.00 161.00   1.00    2.32    --  112.00  61.00 150.00   78
 56  \w     79.00 106.00   1.00    2.32    --  112.00  77.00 150.00   27
 57  \w    133.00 176.00   1.00    2.32    --  112.00  77.00-150.00   43
 58  \w     84.00 109.00   1.00    2.32    --  112.00  61.00-150.00   25
 59  \w     79.00 131.00   1.00    2.32    --  112.00  77.00-150.00   52
 60  \w     80.00 116.00   1.00    2.32    --  112.00-111.00  90.00   36
 61  \w    117.00 153.00   1.00    2.32    --  112.00  61.00  90.00   36
 62  \w     84.00 114.00   1.00    2.32    --  112.00  61.00  90.00   30
 63  \w    120.00 147.00   1.00    2.32    --  112.00  61.00-150.00   27
 64  \w     48.00  75.00   1.00    2.32    --  112.00-111.00  90.00   27
 65  \w     37.00  96.00   1.00    2.32    --  112.00-111.00 -30.00   59
 66  \w     83.00 131.00   1.00    2.32    --  112.00  61.00-120.00   48
 67  \w     80.00 155.00   1.00    2.32    --  112.00  77.00  90.00   75
 68  \w     83.00 112.00   1.00    2.32    --  112.00  61.00  60.00   29
 69  \w    113.00 162.00   1.00    2.32    --  112.00  61.00  60.00   49
 70  \w     83.00 128.00   1.00    2.32    --  112.00  61.00-180.00   45
 71  \w    111.00 178.00   1.00    2.32    --  112.00  77.00-180.00   67
 72  \w    138.00 172.00   1.00    2.32    --  112.00  77.00 -90.00   34
 73  \w     85.00 147.00   1.00    2.32    --  112.00  61.00 120.00   62
 74  \w     83.00 111.00   1.00    2.32    --  112.00  61.00 -60.00   28
 75  \w     79.00 105.00   1.00    2.32    --  112.00  77.00 -90.00   26
 76  \w    127.00 178.00   1.00    2.32    --  112.00  77.00 120.00   51
 77  \w     83.00 111.00   1.00    2.32    --  112.00-111.00 -90.00   28
 78  \w     40.00  87.00   1.00    2.32    --  112.00-111.00 -60.00   47
 79  \w     79.00 106.00   1.00    2.32    --  112.00  77.00 120.00   27
 80  \w     40.00 115.00   1.00    2.32    --  112.00-111.00   0.00   75
 81  \w     79.00 105.00   1.00    2.32    --  112.00  77.00   0.00   26
 82  \w     79.00 104.00   1.00    2.32    --  112.00  77.00  60.00   25
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, AtlasS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0736560000
_diffrn_orient_matrix_UB_12      -0.1859729000
_diffrn_orient_matrix_UB_13      0.0147926000
_diffrn_orient_matrix_UB_21      -0.0062919000
_diffrn_orient_matrix_UB_22      -0.0549761000
_diffrn_orient_matrix_UB_23      -0.0801541000
_diffrn_orient_matrix_UB_31      0.1328456000
_diffrn_orient_matrix_UB_32      -0.1057775000
_diffrn_orient_matrix_UB_33      0.0156921000
_diffrn_radiation_collimation    '0.2 mm sinlge-pinhole'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0329
_diffrn_reflns_av_unetI/netI     0.0221
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            27411
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.992
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.581
_diffrn_reflns_theta_min         2.380
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.280
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.77721
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.44a (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.651
_exptl_crystal_description       plate
_exptl_crystal_F_000             684
_exptl_crystal_size_max          0.19
_exptl_crystal_size_mid          0.07
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.245
_refine_diff_density_min         -0.196
_refine_diff_density_rms         0.039
_refine_ls_abs_structure_details
;
 Flack x determined using 2408 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.04(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.027
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     426
_refine_ls_number_reflns         5504
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.027
_refine_ls_R_factor_all          0.0246
_refine_ls_R_factor_gt           0.0241
_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^)+(0.0407P)^2^+0.2223P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0655
_refine_ls_wR_factor_ref         0.0659
_reflns_Friedel_coverage         0.832
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.984
_reflns_number_gt                5389
_reflns_number_total             5504
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            2c-CIF.cif
_cod_data_source_block           exp_692
_cod_original_formula_sum        'C11 H16 F2 N5 O4.50'
_cod_database_code               1552561
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         C11H13F2N5O3
_reflns_odcompleteness_completeness 100.00
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     74.33
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H) groups
 At 1.5 times of:
  All O(H) groups, All O(H,H) groups
2.a Free rotating group:
 O008(H00I,H00J), O00D(H00M,H00N)
2.b Ternary CH refined with riding coordinates:
 C00U(H00U), C00Z(H00Z), C010(H010), C011(H011), C013(H013), C014(H014),
 C017(H017), C019(H019)
2.c Secondary CH2 refined with riding coordinates:
 C00Y(H00D,H00E), C018(H01A,H01B)
2.d Aromatic/amide H refined with riding coordinates:
 C00Q(H00Q), C00V(H00V), C012(H012), C015(H015)
2.e X=CH2 refined with riding coordinates:
 N00J(H00A,H00C), N00N(H00G,H00H)
2.f Idealised tetrahedral OH refined as rotating group:
 O005(H005), O006(H006), O007(H007), O009(H009), O00A(H00F), O00B(H00B)
;
_shelx_res_checksum              34860
_shelx_hkl_checksum              72419
_olex2_date_sample_data_collection 2017-01-25
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.265
_oxdiff_exptl_absorpt_empirical_full_min 0.741