Design and synthesis of N-substituted-2-butyl-4-chloro-1H-imidazole derivatives as potential ACE inhibitors: in vitro study, in-silico analysis, and a multifaceted CSD-supported crystallographic investigation
R., Manjunath; Rao, Ashwini; Mahesha,; A. H., Udaya Kumar; Acharya, Sudarshan; Udupa E. G., Padmanabha; Abdul Salam, Abdul Ajees; Hakkimane, Sushruta S.; B. S., Shashikala; N. K., Lokanath; Gaonkar, Santosh L.; RSC Advances 15 (2025) 35077–35098; doi:10.1039/D5RA04675K

data_7250908
_publ_section_title
;
 Design and synthesis of N-substituted-2-butyl-4-chloro-1H-imidazole
 derivatives as potential ACE inhibitors: in vitro study, in-silico
 analysis, and a multifaceted CSD-supported crystallographic investigation
;
_journal_issue                   42
_journal_name_full               'RSC Advances'
_journal_page_first              35077
_journal_page_last               35098
_journal_paper_doi               10.1039/D5RA04675K
_journal_volume                  15
_journal_year                    2025
_chemical_formula_moiety         'C17 H23 Cl N2 O2'
_chemical_formula_sum            'C17 H23 Cl N2 O2'
_chemical_formula_weight         322.82
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2025-09-01
_audit_creation_method
;
Olex2 1.5
(compiled 2025.07.13 svn.rb7424aed for OlexSys, GUI svn.r7314)
;
_audit_update_record
;
2025-09-07 deposited with the CCDC.	2025-09-09 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.920(5)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   11.2517(5)
_cell_length_b                   13.8607(6)
_cell_length_c                   11.2925(7)
_cell_measurement_reflns_used    6664
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      27.4210
_cell_measurement_theta_min      1.8000
_cell_volume                     1754.65(15)
_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)'
_diffrn_ambient_temperature      293
_diffrn_detector_area_resol_mean 10.0000
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_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      2.00  44.00   0.70   12.00    --   13.00  38.00   0.00   60
  2  \w     67.00  93.60   0.70   12.00    --   13.00  38.00   0.00   38
  3  \w    -16.00  21.80   0.70   12.00    --   13.00  57.00   0.00   54
  4  \w     31.00  65.30   0.70   12.00    --   13.00  57.00   0.00   49
  5  \w     66.00  92.60   0.70   12.00    --   13.00  57.00   0.00   38
  6  \w    -23.00  42.80   0.70   12.00    --   13.00  38.00-150.00   94
  7  \w     66.00  92.60   0.70   12.00    --   13.00  38.00-150.00   38
  8  \w     -7.00  84.70   0.70   12.00    --   13.00  77.00   0.00  131
  9  \w     41.00  99.80   0.70   12.00    --   13.00  77.00-120.00   84
 10  \w    -16.00 101.60   0.70   12.00    --   13.00  57.00-150.00  168
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Pro II AFC12 (RINC): Kappa single'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0242
_diffrn_reflns_av_unetI/netI     0.0242
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            14146
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.495
_diffrn_reflns_theta_min         1.817
_exptl_absorpt_coefficient_mu    0.226
_exptl_absorpt_correction_T_max  0.958
_exptl_absorpt_correction_T_min  0.949
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.123a (Rigaku Oxford Diffraction, 2022)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            white
_exptl_crystal_density_diffrn    1.222
_exptl_crystal_description       block
_exptl_crystal_F_000             688
_exptl_crystal_size_max          0.23
_exptl_crystal_size_mid          0.22
_exptl_crystal_size_min          0.19
_refine_diff_density_max         0.216
_refine_diff_density_min         -0.365
_refine_diff_density_rms         0.034
_refine_ls_extinction_coef       0.0033(10)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.046
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     252
_refine_ls_number_reflns         3267
_refine_ls_number_restraints     43
_refine_ls_restrained_S_all      1.043
_refine_ls_R_factor_all          0.0646
_refine_ls_R_factor_gt           0.0510
_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^)+(0.0518P)^2^+0.8468P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1293
_refine_ls_wR_factor_ref         0.1382
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2575
_reflns_number_total             3267
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ra04675k2.cif
_cod_data_source_block           lp312_auto
_cod_database_code               7250908
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.958
_shelx_estimated_absorpt_t_min   0.950
_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. Restrained distances
 C14-C15 \\sim C14A-C15A
 with sigma of 0.02
 C15-C16 \\sim C15A-C16A
 with sigma of 0.02
 C16-C17 \\sim C16A-C17A
 with sigma of 0.02
 N1-C14 \\sim N1-C14A
 with sigma of 0.04
 C14-C16 \\sim C14A-C16A
 with sigma of 0.04
 C15-C17 \\sim C15A-C17A
 with sigma of 0.04
 O1-C8 \\sim O3-C8
 with sigma of 0.001
3. Uiso/Uaniso restraints and constraints
C14A \\sim C15A \\sim C16A \\sim C17A: within 2A with sigma of 0.001 and sigma
for terminal atoms of 0.002 within 2A
4. Rigid body (RIGU) restrains
 O3, C8, C7, C9
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
5. Others
 Sof(H8b)=Sof(O3)=Sof(H3)=Sof(C14A)=Sof(H14c)=Sof(H14d)=Sof(C15A)=Sof(H15c)=
 Sof(H15d)=Sof(C16A)=Sof(H16c)=Sof(H16d)=Sof(C17A)=Sof(H17d)=Sof(H17e)=
 Sof(H17f)=1-FVAR(1)
 Sof(O1)=Sof(H1)=Sof(H8a)=Sof(C14)=Sof(H14a)=Sof(H14b)=Sof(C15)=Sof(H15a)=
 Sof(H15b)=Sof(C16)=Sof(H16a)=Sof(H16b)=Sof(C17)=Sof(H17a)=Sof(H17b)=Sof(H17c)=
 FVAR(1)
6.a Ternary CH refined with riding coordinates:
 C8(H8a), C8(H8b)
6.b Secondary CH2 refined with riding coordinates:
 C9(H9a,H9b), C11(H11a,H11b), C14(H14a,H14b), C15(H15a,H15b), C16(H16a,H16b),
 C14A(H14c,H14d), C15A(H15c,H15d), C16A(H16c,H16d)
6.c Aromatic/amide H refined with riding coordinates:
 C6(H6), C1(H1a), C5(H5), C2(H2a)
6.d Idealised Me refined as rotating group:
 C4(H4a,H4b,H4c), C17(H17a,H17b,H17c), C17A(H17d,H17e,H17f)
6.e Idealised tetrahedral OH refined as rotating group:
 O2(H2), O1(H1), O3(H3)
;
_shelx_res_checksum              13955
_olex2_submission_special_instructions 'No special instructions were received'