Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3<i>H</i>)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor.
Huestis, Malcolm P.; Dela Cruz, Darlene; DiPasquale, Antonio G.; Durk, Matthew R.; Eigenbrot, Charles; Gibbons, Paul; Gobbi, Alberto; Hunsaker, Thomas L.; La, Hank; Leung, Dennis H.; Liu, Wendy; Malek, Shiva; Merchant, Mark; Moffat, John G.; Muli, Christine S.; Orr, Christine J.; Parr, Brendan T.; Shanahan, Frances; Sneeringer, Christopher J.; Wang, Weiru; Yen, Ivana; Yin, Jianping; Siu, Michael; Rudolph, Joachim; Journal of medicinal chemistry  (2021) –; doi:10.1021/acs.jmedchem.0c02085

data_1561377
_publ_section_title
;
 Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a
 5-Fluoro-4-(3<i>H</i>)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor.
;
_journal_name_full               'Journal of medicinal chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.0c02085
_journal_year                    2021
_chemical_formula_sum            'C23 H28 F N5 O2'
_chemical_formula_weight         425.50
_chemical_name_common            'Compound 6'
_chemical_name_systematic        'Compound 6'
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_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
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_atom_sites_solution_secondary   difmap
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_cell_angle_beta                 89.776(4)
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_computing_cell_refinement       'Bruker SAINT'
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_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       'phi and omega scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0631
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_diffrn_refln_scan_rate          30
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_diffrn_reflns_limit_l_min       -13
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_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.996
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_diffrn_reflns_theta_max         25.371
_diffrn_reflns_theta_min         1.814
_diffrn_source                   'microfocus sealed tube'
_exptl_absorpt_coefficient_mu    0.089
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_exptl_absorpt_correction_T_min  0.833
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   SADABS
_exptl_crystal_colour            colorless
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_exptl_crystal_description       blade
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_refine_ls_extinction_method     none
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_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     285
_refine_ls_number_reflns         4095
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.031
_refine_ls_R_factor_all          0.1086
_refine_ls_R_factor_gt           0.0510
_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^)+(0.0572P)^2^+0.0509P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1125
_refine_ls_wR_factor_ref         0.1375
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2405
_reflns_number_total             4095
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm0c02085_si_002.cif
_cod_data_source_block           cpd6
_cod_original_cell_volume        1118.24(11)
_cod_database_code               1561377
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_min   0.993
_shelx_estimated_absorpt_t_max   0.998
_shelx_res_checksum              74706
_shelx_hkl_checksum              78702