Metal-Free Synthesis of N-fused Quinazolino-quinazoline-diones as MALAT1 RNA triple helix Intercalator
Pathi , Vijay Babu; Das, Pranotosh; Guin, Abhyuday; Debnath, Manish; Banerji, Biswadip; RSC Medicinal Chemistry  (2024) –; doi:10.1039/D4MD00614C

data_7249484
_publ_section_title
;
 Metal-Free Synthesis of N-fused Quinazolino-quinazoline-diones as MALAT1
 RNA triple helix Intercalator
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D4MD00614C
_journal_year                    2024
_chemical_formula_moiety         'C21 H14 N4 O2'
_chemical_formula_sum            'C21 H14 N4 O2'
_chemical_formula_weight         354.371
_chemical_name_systematic
6-(pyridin-4-ylmethyl)-5H-quinazolino[3,2-a]quinazoline-5,12(6H)-dione
_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_Int_Tables_number      2
_audit_creation_date             2023-12-12
_audit_creation_method
;
Olex2 1.5-beta
(compiled 2023.08.24 svn.re1ec1418 for OlexSys, GUI svn.r6817)
;
_audit_update_record
;
2024-05-21 deposited with the CCDC.	2024-10-21 downloaded from the CCDC.
;
_cell_angle_alpha                65.804(1)
_cell_angle_beta                 74.301(2)
_cell_angle_gamma                72.465(2)
_cell_formula_units_Z            2
_cell_length_a                   7.3072(3)
_cell_length_b                   10.6416(4)
_cell_length_c                   12.3542(4)
_cell_measurement_reflns_used    9663
_cell_measurement_temperature    297.00
_cell_measurement_theta_max      66.550
_cell_measurement_theta_min      6.648
_cell_volume                     823.52(5)
_computing_cell_refinement       'SAINT V8.40B (?, 2016)'
_computing_data_collection       'Bruker APEX3 ver.2018.7-2(Bruker AXS)'
_computing_data_reduction        'SAINT V8.40B (?, 2016)'
_computing_molecular_graphics    'Bruker ShelXLe(Huebschle et all. 2011)'
_computing_publication_material  'Bruker ShelXLe(Huebschle et all. 2011)'
_computing_structure_refinement  'SHELXL-2018/3 (Sheldrick 2018)'
_computing_structure_solution    'SHELXT 2014/5(Sheldrick 2014)'
_diffrn_ambient_temperature      297.00
_diffrn_detector                 'CPAD area detector'
_diffrn_detector_area_resol_mean 7.407
_diffrn_detector_type            'Bruker Photon III'
_diffrn_measured_fraction_theta_full 0.9816
_diffrn_measured_fraction_theta_max 0.9816
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_collimation    '0.5 mm double-pinhole'
_diffrn_radiation_monochromator  'mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0918
_diffrn_reflns_av_unetI/netI     0.0524
_diffrn_reflns_Laue_measured_fraction_full 0.9816
_diffrn_reflns_Laue_measured_fraction_max 0.9816
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            29889
_diffrn_reflns_point_group_measured_fraction_full 0.9816
_diffrn_reflns_point_group_measured_fraction_max 0.9816
_diffrn_reflns_theta_full        66.8829
_diffrn_reflns_theta_max         66.88
_diffrn_reflns_theta_min         6.65
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_current           1.2
_diffrn_source_power             0.06
_diffrn_source_type              'Incoatec I\ms Diamond'
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.776
_exptl_absorpt_correction_T_max  0.7528
_exptl_absorpt_correction_T_min  0.4224
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1673 before and 0.1199 after correction.
The Ratio of minimum to maximum transmission is 0.5611.
The \l/2 correction factor is Not present.
;
_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    1.429
_exptl_crystal_description       needle
_exptl_crystal_F_000             369.277
_exptl_crystal_recrystallization_method 'Slow evaporation of solvent'
_exptl_crystal_size_max          0.24
_exptl_crystal_size_mid          0.21
_exptl_crystal_size_min          0.17
_refine_diff_density_max         0.4346
_refine_diff_density_min         -0.2925
_refine_diff_density_rms         0.0802
_refine_ls_d_res_high            0.8382
_refine_ls_d_res_low             6.6589
_refine_ls_extinction_coef       0.33(4)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_goodness_of_fit_ref   1.2779
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_constraints    27
_refine_ls_number_parameters     245
_refine_ls_number_reflns         2878
_refine_ls_number_restraints     5
_refine_ls_restrained_S_all      1.2767
_refine_ls_R_factor_all          0.1230
_refine_ls_R_factor_gt           0.1107
_refine_ls_shift/su_max          -0.0008
_refine_ls_shift/su_mean         0.0002
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.2P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2912
_refine_ls_wR_factor_ref         0.3116
_reflns_Friedel_coverage         0.0
_reflns_limit_h_max              8
_reflns_limit_h_min              -8
_reflns_limit_k_max              12
_reflns_limit_k_min              -11
_reflns_limit_l_max              14
_reflns_limit_l_min              0
_reflns_number_gt                2232
_reflns_number_total             2878
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            d4md00614c2.cif
_cod_data_source_block           BBVB_300_0m_a
_cod_database_code               7249484
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
2. Restrained distances
 O001-C00D
 with sigma of 0.02
 O003-C00J
 with sigma of 0.02
3. Rigid body (RIGU) restrains
 O001, O003
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 C00R, C00M
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
4.a Secondary CH2 refined with riding coordinates:
 C00G(H00a,H00b)
4.b Aromatic/amide H refined with riding coordinates:
 C00E(H00E), C00F(H00F), C00H(H00H), C00I(H00I), C00K(H00K), C00L(H00L),
 C00M(H00M), C00N(H00N), C00O(H00O), C00P(H00P), C00Q(H00Q), C00R(H00R)
;
_olex2_submission_special_instructions 'No special instructions were received'