Assessment of the structure-activity relationship of analogs of the Naegleria fowleri enolase inhibitor HEX
Kwain, Samuel; Morris, James W. D.; McKeon, Jillian Elisa Milanes; Roster, Colm P.; Noori, Monireh; Gibbs, Aysiah R.; Stevenson III, Robert L; McMillen, Colin; Dominy, Brian N.; Morris, James C.; Whitehead, Daniel Charles; RSC Medicinal Chemistry  (2025) –; doi:10.1039/D5MD00277J

data_7250443
_publ_section_title
;
 Assessment of the structure-activity relationship of analogs of the
 Naegleria fowleri enolase inhibitor HEX
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D5MD00277J
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_sum            'C5 H13 N2 O5 P'
_chemical_formula_weight         212.14
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2016/6
_audit_update_record
;
2025-03-27 deposited with the CCDC.	2025-05-19 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.1084(3)
_cell_length_b                   8.9906(5)
_cell_length_c                   15.9200(9)
_cell_measurement_reflns_used    9959
_cell_measurement_temperature    150(2)
_cell_measurement_theta_max      27.88
_cell_measurement_theta_min      3.42
_cell_volume                     874.30(8)
_computing_cell_refinement       'SAINT v8.37a (Bruker, 2016)'
_computing_data_collection       'APEX3 v2017.3 (Bruker, 2017)'
_computing_data_reduction        'SAINT v8.37a (Bruker, 2016)'
_computing_molecular_graphics    'Mercury 2021.3.0 (Macrae et al. 2020)'
_computing_publication_material  'PublCIF v1.9.21_c (Westrip, 2010)'
_computing_structure_refinement  'SHELXL-2016/6 (Sheldrick, 2015b)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2015a)'
_diffrn_ambient_temperature      150(2)
_diffrn_measured_fraction_theta_full 0.995
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device_type  'Bruker D8 Quest Photon 3'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0725
_diffrn_reflns_av_unetI/netI     0.0249
_diffrn_reflns_Laue_measured_fraction_full 0.995
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            48153
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.998
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.944
_diffrn_reflns_theta_min         3.418
_diffrn_source                   'Incoatec I\mS'
_exptl_absorpt_coefficient_mu    0.310
_exptl_absorpt_correction_T_max  1.0000
_exptl_absorpt_correction_T_min  0.9257
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS 2014/5 (Krause et al., 2015)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.612
_exptl_crystal_description       needle
_exptl_crystal_F_000             448
_exptl_crystal_size_max          0.300
_exptl_crystal_size_mid          0.080
_exptl_crystal_size_min          0.030
_refine_diff_density_max         0.403
_refine_diff_density_min         -0.208
_refine_diff_density_rms         0.064
_refine_ls_abs_structure_details
;
 Flack x determined using 799 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.05(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.102
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     142
_refine_ls_number_reflns         2086
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.102
_refine_ls_R_factor_all          0.0331
_refine_ls_R_factor_gt           0.0314
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0472P)^2^+0.1429P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0774
_refine_ls_wR_factor_ref         0.0787
_reflns_Friedel_coverage         0.695
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     1.000
_reflns_number_gt                1995
_reflns_number_total             2086
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md00277j2.cif
_cod_data_source_block           1
_cod_database_code               7250443
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_min   0.913
_shelx_estimated_absorpt_t_max   0.991
_shelx_res_checksum              27340