Synthesis and growth-inhibitory activities of imidazo[5,1-<i>d</i>]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position.
Cousin, David; Hummersone, Marc G.; Bradshaw, Tracey D.; Zhang, Jihong; Moody, Christopher J.; Foreiter, Magdalena B.; Summers, Helen S.; Lewis, William; Wheelhouse, Richard T.; Stevens, Malcolm F. G.; MedChemComm 9 (2018) 545–553; doi:10.1039/c7md00554g

data_7121167
_publ_section_title
;
 Synthesis and growth-inhibitory activities of
 imidazo[5,1-<i>d</i>]-1,2,3,5-tetrazine-8-carboxamides related to the
 anti-tumour drug temozolomide, with appended silicon, benzyl and
 heteromethyl groups at the 3-position.
;
_journal_issue                   3
_journal_name_full               MedChemComm
_journal_page_first              545
_journal_page_last               553
_journal_paper_doi               10.1039/c7md00554g
_journal_volume                  9
_journal_year                    2018
_chemical_formula_moiety         'C9 H14 N6 O2 Si'
_chemical_formula_sum            'C9 H14 N6 O2 Si'
_chemical_formula_weight         266.35
_chemical_properties_physical    Moisture-sensitive
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     iterative
_atom_sites_solution_secondary   difmap
_audit_creation_date             2015-04-01
_audit_creation_method
;
Olex2 1.2
(compiled 2015.01.26 svn.r3150 for OlexSys, GUI svn.r4998)
;
_audit_update_record
;
2017-10-30 deposited with the CCDC.
2018-01-19 downloaded from the CCDC.
;
_cell_angle_alpha                82.559(9)
_cell_angle_beta                 81.097(9)
_cell_angle_gamma                72.642(10)
_cell_formula_units_Z            2
_cell_length_a                   6.0637(7)
_cell_length_b                   6.3295(8)
_cell_length_c                   17.0569(17)
_cell_measurement_reflns_used    2090
_cell_measurement_temperature    120(2)
_cell_measurement_theta_max      74.9770
_cell_measurement_theta_min      7.3740
_cell_volume                     614.89(13)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2008)'
_computing_structure_solution    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      120(2)
_diffrn_crystal_treatment        'flash frozen in gaseous N2'
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.3613
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.965
_diffrn_measured_fraction_theta_max 0.927
_diffrn_measurement_details
;
  1 omega -112.00  -15.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -      -38.5000  -77.0000 -120.0000 97

  2 omega  -11.00   18.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -      -38.5000   77.0000    0.0000 29

  3 omega  -66.00  -21.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -      -38.5000   77.0000    0.0000 45

  4 omega  -29.00    4.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       42.6277  -38.0000   90.0000 33

  5 omega   27.00   54.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       42.6277 -125.0000   90.0000 27

  6 omega    6.00   55.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       42.6277  -38.0000   90.0000 49

  7 omega   65.00  115.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822 -125.0000   60.0000 50

  8 omega   33.00   86.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822  -30.0000  -60.0000 53

  9 omega   62.00  137.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822   15.0000  -90.0000 75

 10 omega   38.00  125.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822  -77.0000 -150.0000 87

 11 omega   32.00   63.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822  -95.0000  150.0000 31

 12 omega   64.00  105.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822  -95.0000  150.0000 41

 13 omega   56.00   89.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822  -30.0000 -120.0000 33

 14 omega   84.00  146.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822   30.0000  -60.0000 62

 15 omega   37.00   69.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822  -30.0000  120.0000 32

 16 omega  147.00  176.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822   30.0000  -60.0000 29

 17 omega   33.00   80.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822  -30.0000   30.0000 47

 18 omega   32.00  108.00   1.0000   80.0000
omega____ theta____ kappa____ phi______ frames
    -      107.3822  -95.0000   60.0000 76

 19 omega   16.00  113.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       42.6277   57.0000  150.0000 97

 20 omega   11.00   50.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       42.6277   77.0000  -30.0000 39

 21 omega   20.00  115.00   1.0000   20.0000
omega____ theta____ kappa____ phi______ frames
    -       42.6277   38.0000   90.0000 95
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_measurement_specimen_support 'MiTeGen micromount'
_diffrn_orient_matrix_UB_11      0.1388861000
_diffrn_orient_matrix_UB_12      -0.2476376000
_diffrn_orient_matrix_UB_13      0.0051437000
_diffrn_orient_matrix_UB_21      0.0665283000
_diffrn_orient_matrix_UB_22      0.0161253000
_diffrn_orient_matrix_UB_23      -0.0910239000
_diffrn_orient_matrix_UB_31      0.2195961000
_diffrn_orient_matrix_UB_32      0.0629061000
_diffrn_orient_matrix_UB_33      0.0105690000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_unetI/netI     0.0336
_diffrn_reflns_Laue_measured_fraction_full 0.965
_diffrn_reflns_Laue_measured_fraction_max 0.927
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -7
_diffrn_reflns_number            2327
_diffrn_reflns_point_group_measured_fraction_full 0.965
_diffrn_reflns_point_group_measured_fraction_max 0.927
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.613
_diffrn_reflns_theta_min         5.270
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.768
_exptl_absorpt_correction_T_max  0.898
_exptl_absorpt_correction_T_min  0.613
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
Numerical absorption correction based on gaussian integration over
            a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.439
_exptl_crystal_description       plate
_exptl_crystal_F_000             280
_exptl_crystal_size_max          0.3771
_exptl_crystal_size_mid          0.2509
_exptl_crystal_size_min          0.0598
_refine_diff_density_max         0.929
_refine_diff_density_min         -0.481
_refine_diff_density_rms         0.106
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.074
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     173
_refine_ls_number_reflns         2327
_refine_ls_number_restraints     2
_refine_ls_restrained_S_all      1.074
_refine_ls_R_factor_all          0.0905
_refine_ls_R_factor_gt           0.0825
_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^)+(0.0838P)^2^+2.9197P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2166
_refine_ls_wR_factor_ref         0.2225
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2020
_reflns_number_total             2327
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7md00554g2.cif
_cod_data_source_block           mbfcmb
_cod_depositor_comments
'Adding full bibliography for 7121167--7121168.cif.'
_cod_original_cell_volume        614.88(12)
_cod_database_code               7121167
_nottingham_internal_coll_name   MBFCMB
_nottingham_internal_coll_number 14595
_nottingham_internal_coll_client MBF/CJM
_nottingham_internal_coll_type   custom
_nottingham_internal_coll_frame_method 'omega scans'
_nottingham_internal_coll_frame_time '20.0000, 80.0000'
_nottingham_internal_coll_frame_width 1.0000
_nottingham_internal_coll_user   pczwl
_nottingham_internal_coll_date   13/03/2015
_nottingham_internal_coll_location NOTTS
_nottingham_internal_coll_instrument 'SN, XDA 017/09'
_nottingham_internal_process_date 01/04/2015
_nottingham_internal_process_user pczwl
_nottingham_internal_solution_date 1/4/2015
_nottingham_internal_solution_user pczwl
_nottingham_internal_refinement_date 1/4/2015
_nottingham_internal_refinement_user pczwl
_nottingham_internal_validation_date 1/4/2015
_nottingham_internal_validation_user pczwl
_nottingham_internal_archive_date 2/4/2015
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C9 H14 N6 O2 Si'
_chemical_oxdiff_usercomment
'MBFCMB #14595 SN-463 IN FOMBLIN FILM ON A MICROMOUNT FOR MBF/CJM'
_reflns_odcompleteness_completeness 96.60
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.867(6) 0.133(6)
2. 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 C(H,H,H) groups
3. Restrained distances
 N18-H18B = N18-H18A
 0.88 with sigma of 0.02
4.a Secondary CH2 refined with riding coordinates:
 C11(H11A,H11B)
4.b Aromatic/amide H refined with riding coordinates:
 C8(H8)
4.c Idealised Me refined as rotating group:
 C13(H13A,H13C,H13B), C14(H14C,H14A,H14B), C15(H15C,H15A,H15B)
;
_shelx_res_checksum              7582
_olex2_exptl_crystal_mounting_method 'in fomblin film on a micromount'
_olex2_submission_special_instructions 'No special instructions were received'