Evolution of the Synthesis of AMPK Activators for the Treatment of Diabetic Nephropathy: From Three Preclinical Candidates to the Investigational New Drug PF-06409577
Smith, Aaron C.; Kung, Daniel W.; Shavnya, Andre; Brandt, Thomas A.; Dent, Philip D.; Genung, Nathan E.; Cabral, Shawn; Panteleev, Jane; Herr, Michael; Yip, Ka Ning; Aspnes, Gary E.; Conn, Edward L.; Dowling, Matthew S.; Edmonds, David J.; Edmonds, Ian D.; Fernando, Dilinie P.; Herrinton, Paul M.; Keene, Nandell F.; Lavergne, Sophie Y.; Li, Qifang; Polivkova, Jana; Rose, Colin R.; Thuma, Benjamin A.; Vetelino, Michael G.; Wang, Guoqiang; Weaver, John D.; Widlicka, Daniel W.; Price Wiglesworth, Kristin E.; Xiao, Jun; Zahn, Todd; Zhang, Yingxin; Organic Process Research & Development 22 (2018) 681–; doi:10.1021/acs.oprd.8b00059

data_1552852
_publ_section_title
;
 Evolution of the Synthesis of AMPK Activators for the Treatment of
 Diabetic Nephropathy: From Three Preclinical Candidates to the
 Investigational New Drug PF-06409577
;
_journal_issue                   6
_journal_name_full               'Organic Process Research &amp; Development'
_journal_page_first              681
_journal_paper_doi               10.1021/acs.oprd.8b00059
_journal_volume                  22
_journal_year                    2018
_chemical_absolute_configuration ad
_chemical_formula_sum            'C20 H17 F2 N O3'
_chemical_formula_weight         357.34
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 97.3980(10)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   10.0671(3)
_cell_length_b                   10.4134(3)
_cell_length_c                   16.2840(5)
_cell_measurement_reflns_used    9923
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      70.07
_cell_measurement_theta_min      2.74
_cell_volume                     1692.89(9)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      298(2)
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device_type  'Bruker D8 QUEST'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0326
_diffrn_reflns_av_sigmaI/netI    0.0346
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            16190
_diffrn_reflns_theta_full        70.11
_diffrn_reflns_theta_max         70.11
_diffrn_reflns_theta_min         2.74
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.919
_exptl_absorpt_correction_T_max  0.9301
_exptl_absorpt_correction_T_min  0.7700
_exptl_absorpt_correction_type   empirical
_exptl_crystal_density_diffrn    1.402
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       PLATE
_exptl_crystal_F_000             744
_exptl_crystal_size_max          0.30
_exptl_crystal_size_mid          0.17
_exptl_crystal_size_min          0.08
_refine_diff_density_max         0.219
_refine_diff_density_min         -0.250
_refine_diff_density_rms         0.062
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.04(9)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.052
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     485
_refine_ls_number_reflns         6252
_refine_ls_number_restraints     5
_refine_ls_restrained_S_all      1.052
_refine_ls_R_factor_all          0.0362
_refine_ls_R_factor_gt           0.0347
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0534P)^2^+0.1147P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0876
_refine_ls_wR_factor_ref         0.0894
_reflns_number_gt                5987
_reflns_number_total             6252
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            op8b00059_si_002.cif
_cod_data_source_block           z276
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_chemical_absolute_configuration' value 'AD' was changed
to 'ad' in accordance with the
/home/data/users/saulius/crontab/automatic-downloads/current/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26.

data item '_symmetry_cell_setting' value 'Monoclinic' was changed to
'monoclinic' in accordance with the
/home/data/users/saulius/crontab/automatic-downloads/current/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26.

Automatic conversion script
Id: cif_fix_values 6909 2019-04-08 15:41:33Z antanas 

2022-05-06
Z value and formula fixed to values more according to usual
chemical conventions.                 miguel
;
_cod_original_sg_symbol_H-M      P2(1)
_cod_original_formula_sum        'C40 H34 F4 N2 O6'
_cod_original_formula_units_Z    2
_cod_original_formula_weight     714.69
_cod_database_code               1552852