Biophysical investigation and conformational analysis of p38α kinase inhibitor doramapimod and its analogues
Nasiri, Amir H.; Saxena, Krishna; Bats, Jan W.; Nasiri, Hamid R.; Schwalbe, Harald; Med. Chem. Commun. 7 (2016) 1421–; doi:10.1039/C6MD00262E

data_7119113
_publ_section_title
;
 Biophysical investigation and conformational analysis of p38\a kinase
 inhibitor doramapimod and its analogues
;
_journal_issue                   7
_journal_name_full               'Med. Chem. Commun.'
_journal_page_first              1421
_journal_paper_doi               10.1039/C6MD00262E
_journal_volume                  7
_journal_year                    2016
_chemical_formula_moiety         'C21 H24 Cl N4 O , Cl , H2 O'
_chemical_formula_sum            'C21 H26 Cl2 N4 O2'
_chemical_formula_weight         437.36
_chemical_name_systematic
1-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-3-(4-chlorophenyl)urea
_space_group_IT_number           19
_symmetry_cell_setting           orthorhombic
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_audit_update_record
;
2016-04-14 deposited with the CCDC.
2016-05-25 downloaded from the CCDC.
;
_cell_angle_alpha                90.00
_cell_angle_beta                 90.00
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   5.4909(3)
_cell_length_b                   15.4713(9)
_cell_length_c                   26.0024(15)
_cell_measurement_reflns_used    6278
_cell_measurement_temperature    176(2)
_cell_measurement_theta_max      24
_cell_measurement_theta_min      3
_cell_volume                     2208.9(2)
_computing_cell_refinement       'SAINT (Siemens, 1995)'
_computing_data_collection       'SMART (Siemens, 1995)'
_computing_data_reduction        'SAINT (Siemens, 1995)'
_computing_publication_material  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1997)'
_diffrn_ambient_temperature      176(2)
_diffrn_measured_fraction_theta_full 0.990
_diffrn_measured_fraction_theta_max 0.966
_diffrn_measurement_device_type  SIEMENS_SMART_CCD
_diffrn_measurement_method       \w
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'normal-focus sealed tube'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0452
_diffrn_reflns_av_sigmaI/netI    0.0461
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       20
_diffrn_reflns_limit_k_min       -20
_diffrn_reflns_limit_l_max       33
_diffrn_reflns_limit_l_min       -33
_diffrn_reflns_number            25147
_diffrn_reflns_theta_full        27.50
_diffrn_reflns_theta_max         27.99
_diffrn_reflns_theta_min         1.53
_diffrn_standards_decay_%        0.0
_diffrn_standards_interval_time  1200
_diffrn_standards_number         371
_exptl_absorpt_coefficient_mu    0.318
_exptl_absorpt_correction_T_max  0.963
_exptl_absorpt_correction_T_min  0.926
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Sheldrick, 2000)'
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.315
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       rod
_exptl_crystal_F_000             920
_exptl_crystal_size_max          0.65
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.279
_refine_diff_density_min         -0.201
_refine_diff_density_rms         0.045
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.01(5)
_refine_ls_extinction_coef       0.0048(7)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     SHELXL
_refine_ls_goodness_of_fit_ref   1.078
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     287
_refine_ls_number_reflns         5022
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.078
_refine_ls_R_factor_all          0.0612
_refine_ls_R_factor_gt           0.0467
_refine_ls_shift/su_max          0.010
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.03P)^2^+0.6P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0793
_refine_ls_wR_factor_ref         0.0832
_reflns_d_resolution_high        0.7571
_reflns_number_gt                4317
_reflns_number_total             5022
_reflns_threshold_expression     I>2sigma(I)
_cod_data_source_file            c6md00262e1.cif
_cod_data_source_block           compound-6HCl
_cod_database_code               7119113
_shelx_title                     ' km in P2(1)2(1)2(1)'
_shelx_refln_list_code           4
_shelx_f_calc_maximum            164.06