Synthesis and Pharmacological Evaluation of Tetrahydro-γ-carboline Derivatives as Potent Anti-inflammatory Agents Targeting Cyclic GMP‒AMP Synthase
Tan, Jing; Wu, Bing; Chen, Tingting; Fan, Chen; Zhao, Jiannan; Xiong, Chaodong; Feng, Chunlan; Xiao, Ruoxuan; Ding, Chunyong; Tang, Wei; Zhang, Ao; Journal of Medicinal Chemistry  (2021) –; doi:10.1021/acs.jmedchem.1c00398

data_1562964
_publ_section_title
;
 Synthesis and Pharmacological Evaluation of Tetrahydro-\g-carboline
 Derivatives as Potent Anti-inflammatory Agents Targeting Cyclic GMP--AMP
 Synthase
;
_journal_name_full               'Journal of Medicinal Chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.1c00398
_journal_year                    2021
_chemical_formula_moiety         'C20 H17 Cl2 N3 O3'
_chemical_formula_sum            'C20 H17 Cl2 N3 O3'
_chemical_formula_weight         418.26
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2020-05-21
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 96.065(10)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   10.138(4)
_cell_length_b                   14.487(6)
_cell_length_c                   25.836(8)
_cell_measurement_reflns_used    3624
_cell_measurement_temperature    299
_cell_measurement_theta_max      23.896
_cell_measurement_theta_min      2.458
_cell_volume                     3773(2)
_computing_cell_refinement       'SAINT V8.40A (?, 2016)'
_computing_data_reduction        'SAINT V8.40A (?, 2016)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      299.0
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.986
_diffrn_measurement_device_type  'D8 VENTURE'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0884
_diffrn_reflns_av_unetI/netI     0.1024
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.986
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       31
_diffrn_reflns_limit_l_min       -32
_diffrn_reflns_number            23546
_diffrn_reflns_point_group_measured_fraction_full 0.996
_diffrn_reflns_point_group_measured_fraction_max 0.986
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.498
_diffrn_reflns_theta_min         2.091
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.372
_exptl_absorpt_correction_T_max  0.7454
_exptl_absorpt_correction_T_min  0.4935
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1049 before and 0.0714 after correction. The Ratio of minimum to maximum transmission is 0.6621. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.473
_exptl_crystal_description       block
_exptl_crystal_F_000             1728
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.08
_exptl_crystal_size_min          0.05
_refine_diff_density_max         1.519
_refine_diff_density_min         -0.388
_refine_diff_density_rms         0.078
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.031
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     507
_refine_ls_number_reflns         7714
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.031
_refine_ls_R_factor_all          0.1688
_refine_ls_R_factor_gt           0.0819
_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^)+(0.1184P)^2^+2.2283P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2027
_refine_ls_wR_factor_ref         0.2609
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3729
_reflns_number_total             7714
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm1c00398_si_004.cif
_cod_data_source_block           mo_22020225_0m
_cod_database_code               1562964
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.982
_shelx_estimated_absorpt_t_min   0.946
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All O(H) groups
2.a Riding coordinates:
 N2(H2)
2.b Ternary CH refined with riding coordinates:
 C11(H11), C18(H18), C34(H34), C29(H29)
2.c Secondary CH2 refined with riding coordinates:
 C9(H9A,H9B), C31(H31A,H31B), C10(H10A,H10B), C30(H30A,H30B), C20(H20A,H20B),
 C32(H32A,H32B)
2.d Aromatic/amide H refined with riding coordinates:
 N6(H6), N1(H1), N4(H4A), C37(H37), C24(H24), C16(H16), C38(H38), C3(H3A),
 C4(H4), C23(H23), C13(H13), C15(H15), C39(H39), C40(H40), C14(H14)
2.e Idealised tetrahedral OH refined as rotating group:
 O3(H3), O5(H5)
;
_olex2_submission_special_instructions 'No special instructions were received'