High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide <i>N</i>-Methyltransferase (NNMT).
Policarpo, Rocco L.; Decultot, Ludovic; May, Elizabeth; Kuzmič, Petr; Carlson, Samuel; Huang, Danny; Chu, Vincent; Wright, Brandon A.; Dhakshinamoorthy, Saravanakumar; Kannt, Aimo; Rani, Shilpa; Dittakavi, Sreekanth; Panarese, Joseph D.; Gaudet, Rachelle; Shair, Matthew D.; Journal of medicinal chemistry  (2019) –; doi:10.1021/acs.jmedchem.9b01238

data_1552489
_publ_section_title
;
 High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide
 <i>N</i>-Methyltransferase (NNMT).
;
_journal_name_full               'Journal of medicinal chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.9b01238
_journal_year                    2019
_chemical_absolute_configuration ad
_chemical_formula_sum            'C26 H30 F3 N7 O9'
_chemical_formula_weight         641.57
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_symmetry_space_group_name_Hall  'P 1'
_symmetry_space_group_name_H-M   'P 1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                103.0375(11)
_cell_angle_beta                 90.8460(9)
_cell_angle_gamma                90.3108(10)
_cell_formula_units_Z            1
_cell_length_a                   5.05910(10)
_cell_length_b                   10.9615(2)
_cell_length_c                   13.2000(3)
_cell_measurement_reflns_used    9932
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      65.7
_cell_measurement_theta_min      3.44
_cell_volume                     713.03(3)
_computing_cell_refinement       'SAINT 8.37A (Bruker-AXS, 2015)'
_computing_data_reduction        'SAINT 8.37A (Bruker-AXS, 2015)'
_computing_molecular_graphics    'Bruker SHELXTL (Sheldrick, 2015)'
_computing_publication_material  'Bruker SHELXTL (Sheldrick, 2015)'
_computing_structure_refinement  'SHELXL-2014 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT-2014 (Sheldrick, 2015)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.959
_diffrn_measured_fraction_theta_max 0.959
_diffrn_measurement_device_type
;
Bruker D8 goniometer with CCD area detector  
;
_diffrn_measurement_method       'omega and phi scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'I\mS microfocus tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0268
_diffrn_reflns_av_unetI/netI     0.0215
_diffrn_reflns_Laue_measured_fraction_full 0.959
_diffrn_reflns_Laue_measured_fraction_max 0.959
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            17748
_diffrn_reflns_point_group_measured_fraction_full 0.865
_diffrn_reflns_point_group_measured_fraction_max 0.865
_diffrn_reflns_theta_full        66.704
_diffrn_reflns_theta_max         66.704
_diffrn_reflns_theta_min         3.437
_exptl_absorpt_coefficient_mu    1.094
_exptl_absorpt_correction_T_max  0.8058
_exptl_absorpt_correction_T_min  0.7384
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   sadabs
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.494
_exptl_crystal_description       needle
_exptl_crystal_F_000             334
_exptl_crystal_size_max          0.180
_exptl_crystal_size_mid          0.080
_exptl_crystal_size_min          0.060
_refine_diff_density_max         0.530
_refine_diff_density_min         -0.169
_refine_diff_density_rms         0.036
_refine_ls_abs_structure_details
;
 Flack x determined using 1881 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.06(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.025
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     464
_refine_ls_number_reflns         4335
_refine_ls_number_restraints     9
_refine_ls_restrained_S_all      1.032
_refine_ls_R_factor_all          0.0276
_refine_ls_R_factor_gt           0.0273
_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^)+(0.0551P)^2^+0.0932P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0731
_refine_ls_wR_factor_ref         0.0734
_reflns_Friedel_coverage         0.803
_reflns_Friedel_fraction_full    0.770
_reflns_Friedel_fraction_max     0.770
_reflns_number_gt                4280
_reflns_number_total             4335
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm9b01238_si_006.cif
_cod_data_source_block           NS1TFA-10
_cod_database_code               1552489
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_min   0.827
_shelx_estimated_absorpt_t_max   0.937
_refine_ls_abs_structure_hooft   -0.00(6)
_shelx_res_checksum              82553
_shelx_hkl_checksum              77485