Design and development of sulfenylated 5-aminopyrazoles as inhibitors of acetylcholinesterase and butyrylcholinesterase: exploring the implication for Aβ1–42 aggregation inhibition in Alzheimer's disease
Rani, Payal; Chahal, Sandhya; Ranolia, Anju; Kiran,; Kumar, Devendra; Kataria, Ramesh; Kumar, Parvin; Singh, Devender; Duhan, Anil; Jha, Vibhu; Wahajuddin, Muhammad; Joshi, Gaurav; Sindhu, Jayant; RSC Medicinal Chemistry  (2025) –; doi:10.1039/D5MD00069F

data_7250289
_publ_section_title
;
 Design and development of sulfenylated 5-aminopyrazoles as inhibitors of
 acetylcholinesterase and butyrylcholinesterase: exploring the implication
 for A\b1--42 aggregation inhibition in Alzheimer's disease
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D5MD00069F
_journal_year                    2025
_chemical_formula_moiety         'C16 H15 N3 S'
_chemical_formula_sum            'C16 H15 N3 S'
_chemical_formula_weight         281.37
_space_group_crystal_system      orthorhombic
_space_group_IT_number           33
_space_group_name_Hall           'P 2c -2n'
_space_group_name_H-M_alt        'P n a 21'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2023-11-03
_audit_creation_method
;
Olex2 1.5
(compiled 2023.08.24 svn.re1ec1418 for OlexSys, GUI svn.r6817)
;
_audit_update_record
;
2023-11-03 deposited with the CCDC.	2025-03-17 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   11.7569(10)
_cell_length_b                   9.4089(9)
_cell_length_c                   26.936(3)
_cell_measurement_reflns_used    3973
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      25.5840
_cell_measurement_theta_min      3.5390
_cell_volume                     2979.6(5)
_computing_cell_refinement
;
CrystalClear-SM Expert 2.0 r7 (Rigaku, 2011)
;
_computing_data_collection
;
CrystalClear-SM Expert 2.0 r7 (Rigaku, 2011)
;
_computing_data_reduction
;
CrystalClear-SM Expert 2.0 r7 (Rigaku, 2011)
;
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      293(2)
_diffrn_detector                 CCD
_diffrn_detector_area_resol_mean 28.5714
_diffrn_detector_type            'Rigaku Saturn724+'
_diffrn_measured_fraction_theta_full 0.979
_diffrn_measured_fraction_theta_max 0.975
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w    -79.00 -28.00   0.50   50.49    --   -9.95 164.00 -72.00  102
  2  \w    -34.00   5.00   0.50   50.49    --   10.22 -86.00 -59.00   78
  3  \w     25.00  69.00   0.50   50.49    --   10.22  38.00 -81.00   88
  4  \w    -47.00  -3.00   0.50   50.49    --   -9.95 125.00 -90.00   88
  5  \w    -49.00 -12.00   0.50   50.49    --   10.22 -19.00 150.00   74
  6  \w     -6.00  20.00   0.50   50.49    --   10.22 -19.00 150.00   52
  7  \w      6.00  31.00   0.50   50.49    --   10.22-125.00-180.00   50
;
_diffrn_measurement_device       'AFC12 (Right): Kappa 3 circle'
_diffrn_measurement_device_type  'Rigaku Saturn724+ (2x2 bin mode)'
_diffrn_measurement_method       'profile data from \w-scans'
_diffrn_measurement_specimen_support 'Mitegen 50um'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0528883000
_diffrn_orient_matrix_UB_12      0.0059248000
_diffrn_orient_matrix_UB_13      -0.0319399000
_diffrn_orient_matrix_UB_21      0.0077644000
_diffrn_orient_matrix_UB_22      -0.0253252000
_diffrn_orient_matrix_UB_23      -0.0183913000
_diffrn_orient_matrix_UB_31      -0.0279016000
_diffrn_orient_matrix_UB_32      0.0041774000
_diffrn_orient_matrix_UB_33      -0.0657745000
_diffrn_radiation_collimation    0.3
_diffrn_radiation_monochromator  Confocal
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.2698
_diffrn_reflns_av_unetI/netI     0.1505
_diffrn_reflns_Laue_measured_fraction_full 0.979
_diffrn_reflns_Laue_measured_fraction_max 0.975
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       33
_diffrn_reflns_limit_l_min       -30
_diffrn_reflns_number            11829
_diffrn_reflns_point_group_measured_fraction_full 0.813
_diffrn_reflns_point_group_measured_fraction_max 0.797
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.373
_diffrn_reflns_theta_min         3.159
_diffrn_source                   'Rotating Anode'
_diffrn_source_current           24.0
_diffrn_source_power             1.2
_diffrn_source_target            Mo
_diffrn_source_type              'Rotating Anode'
_diffrn_source_voltage           50.0
_exptl_absorpt_coefficient_mu    0.211
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.64845
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.31d (Rigaku Oxford Diffraction, 2017)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light yellow'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.254
_exptl_crystal_description       block
_exptl_crystal_F_000             1184
_exptl_crystal_preparation       'Slow evaporation'
_exptl_crystal_recrystallization_method Synthesized
_exptl_crystal_size_max          0.16
_exptl_crystal_size_mid          0.14
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.409
_refine_diff_density_min         -0.420
_refine_diff_density_rms         0.087
_refine_ls_abs_structure_details
;
 Flack x determined using 612 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.1(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.984
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     365
_refine_ls_number_reflns         4866
_refine_ls_number_restraints     7
_refine_ls_restrained_S_all      0.983
_refine_ls_R_factor_all          0.1829
_refine_ls_R_factor_gt           0.0949
_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^)+(0.1979P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2448
_refine_ls_wR_factor_ref         0.3321
_reflns_Friedel_coverage         0.600
_reflns_Friedel_fraction_full    0.639
_reflns_Friedel_fraction_max     0.611
_reflns_number_gt                2393
_reflns_number_total             4866
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md00069f2.cif
_cod_data_source_block           rk-j1
_cod_database_code               7250289
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O S'
_shelx_estimated_absorpt_t_max   0.975
_shelx_estimated_absorpt_t_min   0.967
_olex2_refinement_description
;
1. Uiso/Uaniso restraints and constraints
C13 \\sim C12: within 2A with sigma of 0.01 and sigma for terminal atoms of
0.02 within 2A
2.a Rotating group:
 N3(H3A,H3B), N3A(H3AA,H3AB)
2.b Aromatic/amide H refined with riding coordinates:
 C15(H15), C2A(H2A), C6A(H6A), C14(H14), C11A(H11A), C13(H13), C4(H4), C2(H2),
 C12A(H12A), C5A(H5A), C5(H5), C3A(H3AC), C12(H12), C3(H3), C13A(H13A),
 C4A(H4A), C11(H11), C6(H6), C15A(H15A), C14A(H14A)
2.c Idealised Me refined as rotating group:
 C16A(H16D,H16E,H16F), C16(H16A,H16B,H16C)
;
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 2.539
_oxdiff_exptl_absorpt_empirical_full_min 0.477