Fused imidazoles as potential chemical scaffolds for inhibition of heat shock protein 70 and induction of apoptosis. Synthesis and biological evaluation of phenanthro[9,10-d]imidazoles and imidazo[4,5-f][1,10]phenanthrolines.
Patel, Alpa; Sharp, Swee Y.; Hall, Katelan; Lewis, William; Stevens, Malcolm F. G.; Workman, Paul; Moody, Christopher J.; Organic & biomolecular chemistry 14 (2016) 3889–3905; doi:10.1039/c6ob00471g

data_7155056
_publ_section_title
;
 Fused imidazoles as potential chemical scaffolds for inhibition of heat
 shock protein 70 and induction of apoptosis. Synthesis and biological
 evaluation of phenanthro[9,10-d]imidazoles and
 imidazo[4,5-f][1,10]phenanthrolines.
;
_journal_issue                   16
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              3889
_journal_page_last               3905
_journal_paper_doi               10.1039/c6ob00471g
_journal_volume                  14
_journal_year                    2016
_chemical_formula_moiety         'C33 H25 F6 N3 O3, 0.5(C7 H8)'
_chemical_formula_sum            'C36.5 H29 F6 N3 O3'
_chemical_formula_weight         671.63
_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             2016-02-29
_audit_creation_method
;
Olex2 1.2
(compiled 2016.02.19 svn.r3266 for OlexSys, GUI svn.r5155)
;
_audit_update_record
;
2016-03-01 deposited with the CCDC.
2016-03-22 downloaded from the CCDC.
;
_cell_angle_alpha                87.909(3)
_cell_angle_beta                 87.569(3)
_cell_angle_gamma                77.316(2)
_cell_formula_units_Z            2
_cell_length_a                   10.9280(18)
_cell_length_b                   11.7780(19)
_cell_length_c                   13.075(2)
_cell_measurement_reflns_used    5651
_cell_measurement_temperature    90(2)
_cell_measurement_theta_max      27.34
_cell_measurement_theta_min      2.31
_cell_volume                     1639.7(5)
_computing_cell_refinement       'Bruker SAINT version 6.36A (Bruker, 2002)'
_computing_data_collection       'Bruker SMART version 5.625 (Bruker, 2001)'
_computing_data_reduction        'Bruker SAINT; SHELXTL (Sheldrick, 2008)'
_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    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_temperature      90(2)
_diffrn_detector_area_resol_mean 8.366
_diffrn_measured_fraction_theta_full 0.994
_diffrn_measured_fraction_theta_max 0.978
_diffrn_measurement_device_type  'Bruker SMART APEX CCD area detector'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0237
_diffrn_reflns_av_unetI/netI     0.0299
_diffrn_reflns_Laue_measured_fraction_full 0.994
_diffrn_reflns_Laue_measured_fraction_max 0.978
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            14312
_diffrn_reflns_point_group_measured_fraction_full 0.994
_diffrn_reflns_point_group_measured_fraction_max 0.978
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.338
_diffrn_reflns_theta_min         2.306
_diffrn_source                   'sealed tube'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.110
_exptl_absorpt_correction_T_max  0.8621
_exptl_absorpt_correction_T_min  0.8131
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2007/2 (Bruker,2007) was used for absorption correction.
wR2(int) was 0.0607 before and 0.0336 after correction.
The Ratio of minimum to maximum transmission is 0.9432.
The \l/2 correction factor is 0.0015.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.360
_exptl_crystal_description       BLOCK
_exptl_crystal_F_000             694
_exptl_crystal_size_max          0.47
_exptl_crystal_size_mid          0.19
_exptl_crystal_size_min          0.15
_refine_diff_density_max         0.630
_refine_diff_density_min         -0.347
_refine_diff_density_rms         0.059
_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     802
_refine_ls_number_reflns         7237
_refine_ls_number_restraints     812
_refine_ls_restrained_S_all      1.156
_refine_ls_R_factor_all          0.0755
_refine_ls_R_factor_gt           0.0610
_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^)+(0.0929P)^2^+0.6475P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1636
_refine_ls_wR_factor_ref         0.1798
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5578
_reflns_number_total             7237
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c6ob00471g2.cif
_cod_data_source_block           apcjmo
_cod_depositor_comments
'Adding full bibliography for 7155056--7155058.cif.'
_cod_original_formula_sum        'C36.50 H29 F6 N3 O3'
_cod_database_code               7155056
_nottingham_internal_coll_name   APCJMO
_nottingham_internal_coll_number 11441
_nottingham_internal_coll_client AP/CJM
_nottingham_internal_coll_type   sphere
_nottingham_internal_coll_frame_method \w
_nottingham_internal_coll_frame_time 30
_nottingham_internal_coll_frame_width 0.3
_nottingham_internal_coll_user   WL
_nottingham_internal_coll_date   1/5/2012
_nottingham_internal_coll_location NOTTS
_nottingham_internal_process_date 02/05/2012
_nottingham_internal_process_user WL
_nottingham_internal_solution_user wl
_nottingham_internal_refinement_user wl
_nottingham_internal_validation_user wl
_shelx_shelxl_version_number     2014/7
_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. Restrained distances
 C22-C18 \\sim C22A-C18A \\sim C20A-C26A \\sim C20-C26
 with sigma of 0.02
 F23A-C22A \\sim F23-C22 \\sim F25A-C22A \\sim F25-C22 \\sim F24-C22 \\sim
F24A-C22A \\sim F29-C26 ~
 F27-C26 \\sim F28-C26 \\sim F29A-C26A \\sim F28A-C26A \\sim F27A-C26A
 with sigma of 0.02
 F25-F24 \\sim F24-F23 \\sim F23-F25 \\sim F27A-F29A \\sim F29A-F28A \\sim
F28A-F27A \\sim F24A-F25A ~
 F25A-F23A \\sim F23A-F24A \\sim F28-F27 \\sim F27-F29 \\sim F29-F28
 with sigma of 0.02
3. Restrained planarity
 C30, C31A, C32A, C33A, C34A, C35A, O36A
 with sigma of 0.1
 C35, C31, C32, C34, O36, C33, C30
 with sigma of 0.1
 C6A, C7A, C12A, C8A, C9A, C11A, C10A, C13A
 with sigma of 0.1
 C6, C7, C12, C8, C9, C11, C10, C13
 with sigma of 0.1
 C5, C43, C38, C39, C42, C40, C41, O44
 with sigma of 0.1
 C5, C38A, C39A, C43A, C42A, C40A, C41A, O44A
 with sigma of 0.1
 C16, C21, C17, C18, C22, C19, C20, C26, C2
 with sigma of 0.1
 C2, C17A, C16A, C18A, C22A, C19A, C20A, C21A, C26A
 with sigma of 0.1
 C10, C13, N15, O14
 with sigma of 0.1
 C10A, C13A, N15A, O14A
 with sigma of 0.1
4. Rigid bond restraints
 O14, N15, C7, C11, C10, C31, C39, C38, C8, C17, C6, C13, C32, C12, C16, C9,
 C35, O36, C18, C40, C43, C33, O44, C34, C41, C21, C42, C45, C20, C19, C37, C22,
  C26, F23, F24, F25, F29, F27, F28
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
 O36A, C33A, C37A, C34A, C32A, C31A, C35A, C46, C6A, C7A, C12A, C8A, C11A,
 C10A, C13A, C9A, N15A, O14A, C38A, C43A, C42A, C39A, C41A, C40A, O44A, C45A,
 C17A, C18A, C19A, C20A, C21A, C16A, C26A, C22A, F27A, F25A, F23A, F24A, F29A,
 F28A
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
5. Uiso/Uaniso restraints and constraints
O14 \\sim N15 \\sim C7 \\sim C11 \\sim C10 \\sim C31 \\sim C39 \\sim C38 \\sim
C8 \\sim C17 \\sim C6 \\sim C13 \\sim C32 \\sim C12 \\sim C16 \\sim C9 \\sim
C35 \\sim O36 \\sim C18 \\sim C40 \\sim C43 \\sim C33 \\sim O44 \\sim C34 \\sim
C41 \\sim C21 \\sim C42 \\sim C45 \\sim C20 \\sim C19 \\sim C37 \\sim C22 \\sim
C26 \\sim F23 \\sim F24 \\sim F25 \\sim F29 \\sim F27 \\sim F28: within 1.7A
with sigma of 0.008 and sigma for terminal atoms of 0.016
O36A \\sim C33A \\sim C37A \\sim C34A \\sim C32A \\sim C31A \\sim C35A \\sim
C46 \\sim C6A \\sim C7A \\sim C12A \\sim C8A \\sim C11A \\sim C10A \\sim C13A
\\sim C9A \\sim N15A \\sim O14A \\sim C38A \\sim C43A \\sim C42A \\sim C39A
\\sim C41A \\sim C40A \\sim O44A \\sim C45A \\sim C17A \\sim C18A \\sim C19A
\\sim C20A \\sim C21A \\sim C16A \\sim C26A \\sim C22A \\sim F27A \\sim F25A
\\sim F23A \\sim F24A \\sim F29A \\sim F28A: within 1.7A with sigma of 0.008
and sigma for terminal atoms of 0.016
6. Others
 Sof(C31A)=Sof(H31A)=Sof(C32A)=Sof(H32A)=Sof(C33A)=Sof(C34A)=Sof(H34A)=
 Sof(C35A)=Sof(H35A)=Sof(O36A)=Sof(C37A)=Sof(H37d)=Sof(H37e)=Sof(H37f)=1-FVAR(1)
 Sof(C31)=Sof(H31)=Sof(C32)=Sof(H32)=Sof(C33)=Sof(C34)=Sof(H34)=Sof(C35)=
 Sof(H35)=Sof(O36)=Sof(C37)=Sof(H37a)=Sof(H37b)=Sof(H37c)=FVAR(1)
 Sof(C6A)=Sof(H6Aa)=Sof(H6Ab)=Sof(C7A)=Sof(C8A)=Sof(H8A)=Sof(C9A)=Sof(H9A)=
 Sof(C10A)=Sof(C11A)=Sof(H11A)=Sof(C12A)=Sof(H12A)=Sof(C13A)=Sof(O14A)=
 Sof(N15A)=Sof(H15c)=Sof(H15d)=1-FVAR(2)
 Sof(C6)=Sof(H6a)=Sof(H6b)=Sof(C7)=Sof(C8)=Sof(H8)=Sof(C9)=Sof(H9)=Sof(C10)=
 Sof(C11)=Sof(H11)=Sof(C12)=Sof(H12)=Sof(C13)=Sof(O14)=Sof(N15)=Sof(H15a)=
 Sof(H15b)=FVAR(2)
 Sof(C38A)=Sof(C39A)=Sof(H39A)=Sof(C40A)=Sof(H40A)=Sof(C41A)=Sof(C42A)=
 Sof(H42A)=Sof(C43A)=Sof(H43A)=Sof(O44A)=Sof(C45A)=Sof(H45d)=Sof(H45e)=
 Sof(H45f)=1-FVAR(3)
 Sof(C38)=Sof(C39)=Sof(H39)=Sof(C40)=Sof(H40)=Sof(C41)=Sof(C42)=Sof(H42)=
 Sof(C43)=Sof(H43)=Sof(O44)=Sof(C45)=Sof(H45a)=Sof(H45b)=Sof(H45c)=FVAR(3)
 Sof(C16A)=Sof(C17A)=Sof(H17A)=Sof(C18A)=Sof(C19A)=Sof(H19A)=Sof(C20A)=
 Sof(C21A)=Sof(H21A)=Sof(C22A)=Sof(F23A)=Sof(F24A)=Sof(F25A)=Sof(C26A)=
 Sof(F27A)=Sof(F28A)=Sof(F29A)=1-FVAR(4)
 Sof(C16)=Sof(C17)=Sof(H17)=Sof(C18)=Sof(C19)=Sof(H19)=Sof(C20)=Sof(C21)=
 Sof(H21)=Sof(C22)=Sof(F23)=Sof(F24)=Sof(F25)=Sof(C26)=Sof(F27)=Sof(F28)=
 Sof(F29)=FVAR(4)
 Fixed Sof: C46(0.5) H46a(0.5) H46b(0.5) H46c(0.5) H47(0.5)
7.a Secondary CH2 refined with riding coordinates:
 C6(H6a,H6b), C6A(H6Aa,H6Ab)
7.b Aromatic/amide H refined with riding coordinates:
 C8A(H8A), C8(H8), C9(H9), C9A(H9A), C11(H11), C11A(H11A), C12A(H12A),
 C12(H12), C17A(H17A), C17(H17), C19A(H19A), C19(H19), C21A(H21A), C21(H21),
 C31A(H31A), C31(H31), C32(H32), C32A(H32A), C34(H34), C34A(H34A), C35A(H35A),
 C35(H35), C39A(H39A), C39(H39), C40(H40), C40A(H40A), C42A(H42A), C42(H42),
 C43(H43), C43A(H43A), C47(H47), C48(H48), C49(H49)
7.c X=CH2 refined with riding coordinates:
 N15(H15a,H15b), N15A(H15c,H15d)
7.d Idealised Me refined as rotating group:
 C37(H37a,H37b,H37c), C37A(H37d,H37e,H37f), C45(H45a,H45b,H45c), C45A(H45d,
 H45e,H45f), C46(H46a,H46b,H46c)
;
_shelx_res_checksum              5282
_olex2_submission_special_instructions 'No special instructions were received'