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_7121168
_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         'C11 H18 N6 O3 Si'
_chemical_formula_sum            'C11 H18 N6 O3 Si'
_chemical_formula_weight         310.40
_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   geom
_atom_sites_solution_primary     iterative
_atom_sites_solution_secondary   difmap
_audit_creation_date             2015-06-04
_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                88.485(12)
_cell_angle_beta                 78.814(11)
_cell_angle_gamma                86.275(12)
_cell_formula_units_Z            2
_cell_length_a                   7.5168(10)
_cell_length_b                   9.0109(15)
_cell_length_c                   11.4120(15)
_cell_measurement_reflns_used    2659
_cell_measurement_temperature    120(2)
_cell_measurement_theta_max      74.1440
_cell_measurement_theta_min      5.9260
_cell_volume                     756.61(19)
_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 area detector'
_diffrn_detector_area_resol_mean 5.1806
_diffrn_detector_type            'Agilent Diffraction Atlas detector'
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.954
_diffrn_measurement_details
;
  1 omega   52.00  114.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072 -125.0000   60.0000 31

  2 omega   97.00  123.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  -77.0000  -30.0000 13

  3 omega   74.00  176.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072   15.0000  -90.0000 51

  4 omega  110.00  168.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  125.0000   60.0000 29

  5 omega   94.00  168.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  125.0000  -90.0000 37

  6 omega  150.00  176.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  125.0000 -150.0000 13

  7 omega   80.00  170.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072   61.0000  -30.0000 45

  8 omega   53.00   95.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  -45.0000 -180.0000 21

  9 omega   87.00  121.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072 -125.0000 -180.0000 17

 10 omega   46.00   84.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  -30.0000  -60.0000 19

 11 omega   50.00   84.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  -30.0000  -30.0000 17

 12 omega   41.00   81.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  -77.0000  -30.0000 20

 13 omega   36.00   98.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  -45.0000   30.0000 31

 14 omega   37.00   95.00   2.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      105.5072  -77.0000 -180.0000 29

 15 omega  -46.00   28.00   2.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -38.5000   38.0000 -180.0000 37

 16 omega  -64.00   32.00   2.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -38.5000   57.0000   30.0000 48

 17 omega  -89.00  -33.00   2.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -38.5000  125.0000   90.0000 28

 18 omega -106.00  -16.00   2.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -38.5000  -57.0000 -120.0000 45
;
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'SuperNova-Duo, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_measurement_specimen_support 'MiTeGen micromount'
_diffrn_orient_matrix_UB_11      0.0248966000
_diffrn_orient_matrix_UB_12      -0.1710492000
_diffrn_orient_matrix_UB_13      0.0015387000
_diffrn_orient_matrix_UB_21      -0.0323212000
_diffrn_orient_matrix_UB_22      -0.0029979000
_diffrn_orient_matrix_UB_23      -0.1291334000
_diffrn_orient_matrix_UB_31      0.2052922000
_diffrn_orient_matrix_UB_32      0.0096127000
_diffrn_orient_matrix_UB_33      -0.0475628000
_diffrn_radiation_collimation    'focusing mirrors'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_radiation_wavelength_determination fundamental
_diffrn_reflns_av_R_equivalents  0.0278
_diffrn_reflns_av_unetI/netI     0.0395
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.954
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            5157
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.954
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.116
_diffrn_reflns_theta_min         4.919
_diffrn_source                   'microfocus sealed tube'
_diffrn_source_current           0.8
_diffrn_source_power             0.04
_diffrn_source_target            Cu
_diffrn_source_type              'Agilent Diffraction microfocus tube'
_diffrn_source_voltage           50
_exptl_absorpt_coefficient_mu    1.565
_exptl_absorpt_correction_T_max  0.931
_exptl_absorpt_correction_T_min  0.681
_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    1.362
_exptl_crystal_description       plate
_exptl_crystal_F_000             328
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: 1:1 water:acetone'
_exptl_crystal_size_max          0.3666
_exptl_crystal_size_mid          0.2579
_exptl_crystal_size_min          0.0469
_refine_diff_density_max         0.474
_refine_diff_density_min         -0.281
_refine_diff_density_rms         0.060
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.041
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     193
_refine_ls_number_reflns         2945
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.041
_refine_ls_R_factor_all          0.0452
_refine_ls_R_factor_gt           0.0410
_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^)+(0.0646P)^2^+0.2695P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1096
_refine_ls_wR_factor_ref         0.1139
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2656
_reflns_number_total             2945
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7md00554g2.cif
_cod_data_source_block           mbfcme
_cod_depositor_comments
'Adding full bibliography for 7121167--7121168.cif.'
_cod_database_code               7121168
_nottingham_internal_coll_name   MBFCME
_nottingham_internal_coll_number 14847
_nottingham_internal_coll_client MBF/CJM
_nottingham_internal_coll_type   custom
_nottingham_internal_coll_frame_method 'omega scans'
_nottingham_internal_coll_frame_time '3.0000, 2.0000'
_nottingham_internal_coll_frame_width 2.0000
_nottingham_internal_coll_user   pczwl
_nottingham_internal_coll_date   04/06/2015
_nottingham_internal_coll_location NOTTS
_nottingham_internal_coll_instrument 'SN, XDA 017/09'
_nottingham_internal_process_date 04/06/2015
_nottingham_internal_process_user pczwl
_nottingham_internal_solution_date 4/6/2015
_nottingham_internal_solution_user pczwl
_nottingham_internal_refinement_date 4/6/2015
_nottingham_internal_refinement_user pczwl
_nottingham_internal_validation_date 4/6/2015
_nottingham_internal_validation_user pczwl
_nottingham_internal_archive_date 4/6/2015
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C11 H18 N6 O3 Si'
_chemical_oxdiff_usercomment
'MBFCME #14847 SN-566 IN FOMBLIN FILM ON A MICROMOUNT FOR MBF/CJM'
_reflns_odcompleteness_completeness 99.85
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_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 C(H,H,H) groups
2.a Secondary CH2 refined with riding coordinates:
 C11(H11A,H11B), C13(H13A,H13B), C14(H14A,H14B)
2.b Aromatic/amide H refined with riding coordinates:
 C8(H8)
2.c X=CH2 refined with riding coordinates:
 N21(H21A,H21B)
2.d Idealised Me refined as rotating group:
 C16(H16A,H16B,H16C), C17(H17A,H17B,H17C), C18(H18A,H18B,H18C)
;
_shelx_res_checksum              42616
_olex2_exptl_crystal_mounting_method 'in fomblin film on a micromount'
_olex2_submission_special_instructions 'No special instructions were received'