Synthesis and biological evaluation of novel 2,3-pyrazole ring-substituted-4,4-dimethyl lithocholic acid derivatives as selective protein tyrosine phosphatase 1B (PTP1B) inhibitors with cellular efficacy
Mao, Shi-Wei; Shuai, Lin; He, Hai-Bing; Pan, Na; Gao, Li-Xin; Yu, Li-Fang; Li, Jia; Li, Jing-Ya; Yang, Fan; RSC Adv. 5 (2015) 106551–; doi:10.1039/C5RA20238H

data_7223486
_publ_section_title
;
 Synthesis and biological evaluation of novel 2,3-pyrazole
 ring-substituted-4,4-dimethyl lithocholic acid derivatives as selective
 protein tyrosine phosphatase 1B (PTP1B) inhibitors with cellular efficacy
;
_journal_issue                   129
_journal_name_full               'RSC Adv.'
_journal_page_first              106551
_journal_paper_doi               10.1039/C5RA20238H
_journal_volume                  5
_journal_year                    2015
_chemical_absolute_configuration ad
_chemical_compound_source        'lithocholic acid'
_chemical_formula_sum            'C33 H45 Cl N2 O3'
_chemical_formula_weight         553.16
_chemical_name_systematic        MSW-167
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2013
_audit_update_record
;
2015-05-19 deposited with the CCDC.
2015-12-04 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 100.744(6)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   12.474(3)
_cell_length_b                   6.1241(17)
_cell_length_c                   19.930(6)
_cell_measurement_reflns_used    1306
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      49.835
_cell_measurement_theta_min      5.790
_cell_volume                     1495.8(7)
_computing_cell_refinement       'Bruker SMART'
_computing_data_collection       'Bruker SMART'
_computing_data_reduction        'Bruker SHELXTL'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2013 (Sheldrick, 2013)'
_computing_structure_solution    'Bruker SHELXTL'
_diffrn_ambient_temperature      293(2)
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device_type  'CCD area detector'
_diffrn_measurement_method       'phi and omega scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0381
_diffrn_reflns_av_unetI/netI     0.0784
_diffrn_reflns_laue_measured_fraction_full 0.999
_diffrn_reflns_laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            8648
_diffrn_reflns_point_group_measured_fraction_full 0.970
_diffrn_reflns_point_group_measured_fraction_max 0.969
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.486
_diffrn_reflns_theta_min         1.788
_exptl_absorpt_coefficient_mu    0.163
_exptl_absorpt_correction_T_max  0.7457
_exptl_absorpt_correction_T_min  0.5966
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   sadabs
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.228
_exptl_crystal_description       prismatic
_exptl_crystal_F_000             596
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: CHCl3:CH3OH=3:1 / petroleum ether'
_exptl_crystal_size_max          0.176
_exptl_crystal_size_mid          0.101
_exptl_crystal_size_min          0.065
_refine_diff_density_max         0.287
_refine_diff_density_min         -0.140
_refine_diff_density_rms         0.035
_refine_ls_abs_structure_details
; 
 Flack x determined using 943 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons and Flack (2004), Acta Cryst. A60, s61). 
;
_refine_ls_abs_structure_Flack   0.15(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.915
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     393
_refine_ls_number_reflns         5385
_refine_ls_number_restraints     61
_refine_ls_restrained_S_all      0.921
_refine_ls_R_factor_all          0.1150
_refine_ls_R_factor_gt           0.0591
_refine_ls_shift/su_max          0.038
_refine_ls_shift/su_mean         0.003
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0774P)^2^+0.0747P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1311
_refine_ls_wR_factor_ref         0.1582
_reflns_Friedel_coverage         0.763
_reflns_friedel_fraction_full    0.935
_reflns_friedel_fraction_max     0.932
_reflns_number_gt                2990
_reflns_number_total             5385
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c5ra20238h2.cif
_cod_data_source_block           cd214518
_cod_database_code               7223486
_audit_block_doi                 10.5517/cc1j1m4b
_shelxl_version_number           2013-4
_shelx_res_checksum              32933