An Isoform-Selective PTP1B Inhibitor Derived from Nitrogen-Atom Augmentation of Radicicol.
Shi, Taoda; Wijeratne, E. M. Kithsiri; Solano, Cristian; Ambrose, Andrew J.; Ross, Alison B.; Norwood, Charles; Orido, Charles K.; Grigoryan, Tigran; Tillotson, Joseph; Kang, Minjin; Luo, Gang; Keegan, Bradley M.; Hu, Wenhao; Blagg, Brian S. J.; Zhang, Donna D.; Gunatilaka, A. A. Leslie; Chapman, Eli; Biochemistry 58 (2019) 3225–3231; doi:10.1021/acs.biochem.9b00499

data_1552501
_publ_section_title
;
 An Isoform-Selective PTP1B Inhibitor Derived from Nitrogen-Atom
 Augmentation of Radicicol.
;
_journal_issue                   30
_journal_name_full               Biochemistry
_journal_page_first              3225
_journal_page_last               3231
_journal_paper_doi               10.1021/acs.biochem.9b00499
_journal_volume                  58
_journal_year                    2019
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C18 H21 Cl N2 O5'
_chemical_formula_sum            'C18 H21 Cl N2 O5'
_chemical_formula_weight         380.82
_space_group_crystal_system      monoclinic
_space_group_IT_number           5
_space_group_name_Hall           'C 2y'
_space_group_name_H-M_alt        'C 1 2 1'
_symmetry_space_group_name_Hall  'C 2y'
_symmetry_space_group_name_H-M   'C 1 2 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2018-11-21
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 103.59(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   32.35(2)
_cell_length_b                   6.672(4)
_cell_length_c                   8.016(5)
_cell_measurement_reflns_used    2061
_cell_measurement_temperature    100
_cell_measurement_theta_max      25.221
_cell_measurement_theta_min      2.59
_cell_volume                     1681.7(18)
_computing_cell_refinement       'SAINT v8.34A (Bruker, 2013)'
_computing_data_reduction        'SAINT v8.34A (Bruker, 2013)'
_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    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0489
_diffrn_reflns_av_unetI/netI     0.0668
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       39
_diffrn_reflns_limit_h_min       -39
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       9
_diffrn_reflns_limit_l_min       -9
_diffrn_reflns_number            10146
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.996
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.751
_diffrn_reflns_theta_min         1.295
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.262
_exptl_absorpt_correction_T_max  0.7453
_exptl_absorpt_correction_T_min  0.6527
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2014/5 (Bruker,2014/5) was used for absorption correction. wR2(int) was 0.0551 before and 0.0484 after correction. The Ratio of minimum to maximum transmission is 0.8758. The \l/2 correction factor is 0.00150.'
_exptl_crystal_colour            'metallic light colourless'
_exptl_crystal_colour_lustre     metallic
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.504
_exptl_crystal_description       plate
_exptl_crystal_F_000             800
_exptl_crystal_size_max          0.35
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.277
_refine_diff_density_min         -0.242
_refine_diff_density_rms         0.057
_refine_ls_abs_structure_details
;
 Flack x determined using 913 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.14(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.802
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     240
_refine_ls_number_reflns         3212
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      0.802
_refine_ls_R_factor_all          0.0663
_refine_ls_R_factor_gt           0.0430
_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^)+(0.1000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1062
_refine_ls_wR_factor_ref         0.1227
_reflns_Friedel_coverage         0.829
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.993
_reflns_number_gt                2540
_reflns_number_total             3212
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            bi9b00499_si_002.cif
_cod_data_source_block           mo_ts100k_0ma
_cod_original_cell_volume        1681.6(18)
_cod_database_code               1552501
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_max   0.987
_shelx_estimated_absorpt_t_min   0.914
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C17(H17), C11(H11), C14(H14), C15(H15)
2.b Secondary CH2 refined with riding coordinates:
 C13(H13A,H13B), C16(H16A,H16B), C10(H10A,H10B), C12(H12A,H12B)
2.c Aromatic/amide H refined with riding coordinates:
 C4(H4A), C8(H8)
2.d Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C)
2.e Idealised tetrahedral OH refined as rotating group:
 O3(H3), O5(H5), O4(H4), O2(H2)
;
_shelx_res_checksum              16411
_shelx_hkl_checksum              1504
_olex2_submission_special_instructions 'No special instructions were received'