Bisarylthiourea comprising cycloalkyl-thiophene-3-carboxylate derivatives as potential Human Toll-Like Receptor (TLR)2 Agonists: Design, Synthesis, and Structure-Activity Relationship Enabling the Switch from TLR2/1 to TLR2/6 Activation
Chandrakanth, Munugala; Okubo, Yoshikazu Honda; Arya, C. G.; Salunke, Deepak B.; Petrovsky, Nikolai; Banothu, Janardhan; RSC Medicinal Chemistry  (2026) –; doi:10.1039/D5MD01078K

data_7251675
_publ_section_title
;
 Bisarylthiourea comprising cycloalkyl-thiophene-3-carboxylate derivatives
 as potential Human Toll-Like Receptor (TLR)2 Agonists: Design, Synthesis,
 and Structure-Activity Relationship Enabling the Switch from TLR2/1 to
 TLR2/6 Activation
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D5MD01078K
_journal_year                    2026
_chemical_formula_moiety         'C22 H27 N3 O3 S2'
_chemical_formula_sum            'C22 H27 N3 O3 S2'
_chemical_formula_weight         445.58
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2019/3
_audit_update_record
;
2025-10-15 deposited with the CCDC.	2026-02-20 downloaded from the CCDC.
;
_cell_angle_alpha                84.153(3)
_cell_angle_beta                 82.661(3)
_cell_angle_gamma                68.325(3)
_cell_formula_units_Z            2
_cell_length_a                   9.6883(8)
_cell_length_b                   9.9058(7)
_cell_length_c                   12.6922(10)
_cell_measurement_reflns_used    9843
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      27.78
_cell_measurement_theta_min      2.66
_cell_volume                     1120.70(15)
_computing_cell_refinement       'APEX4 V8.40B (Bruker, 2021)'
_computing_data_collection       'APEX4 (Bruker, v2021.4-0)'
_computing_data_reduction        'SAINT/XPREP (Bruker, 2021)'
_computing_publication_material  'SHELXL-2019/3 (Sheldrick, 2019)'
_computing_structure_refinement  'SHELXL-2019/3 (Sheldrick, 2019)'
_computing_structure_solution    'SHELXT-2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      298(2)
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_device_type
'Bruker D8 VENTURE diffractometer equipped with PHOTON II detector'
_diffrn_measurement_method       'omega and phi scans'
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0610
_diffrn_reflns_av_unetI/netI     0.0312
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            45385
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.998
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.992
_diffrn_reflns_theta_min         2.538
_exptl_absorpt_coefficient_mu    0.266
_exptl_absorpt_correction_T_max  0.7456
_exptl_absorpt_correction_T_min  0.5318
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
 SADABS-2016/2 - Bruker AXS area detector scaling and absorption 
 correction
 Reference: Krause, L., Herbst-Irmer, R., Sheldrick G.M. & Stalke D.,
 J. Appl. Cryst. 48 (2015) 3-10.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.320
_exptl_crystal_description       block
_exptl_crystal_F_000             472
_exptl_crystal_size_max          0.409
_exptl_crystal_size_mid          0.196
_exptl_crystal_size_min          0.080
_refine_diff_density_max         0.452
_refine_diff_density_min         -0.403
_refine_diff_density_rms         0.057
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.058
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     307
_refine_ls_number_reflns         4394
_refine_ls_number_restraints     177
_refine_ls_restrained_S_all      1.095
_refine_ls_R_factor_all          0.0654
_refine_ls_R_factor_gt           0.0531
_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^)+(0.0783P)^2^+0.7887P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1415
_refine_ls_wR_factor_ref         0.1555
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3619
_reflns_number_total             4394
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md01078k2.cif
_cod_data_source_block           TMC1-12
_cod_database_code               7251675
_shelx_shelxl_version_number     2019/3
_shelx_estimated_absorpt_t_min   0.899
_shelx_estimated_absorpt_t_max   0.979
_shelx_res_checksum              4108