Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics.
Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of medicinal chemistry 60 (2017) 3606–3617; doi:10.1021/acs.jmedchem.7b00254

data_1545900
_publ_section_title
;
 Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol
 Derivatives as General Anesthetics.
;
_journal_issue                   9
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              3606
_journal_page_last               3617
_journal_paper_doi               10.1021/acs.jmedchem.7b00254
_journal_volume                  60
_journal_year                    2017
_chemical_formula_moiety         'C25 H31 N O2'
_chemical_formula_sum            'C25 H31 N O2'
_chemical_formula_weight         377.51
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2015-03-09
_audit_creation_method
;
Olex2 1.2
(compiled 2013.11.15 svn.r2834 for OlexSys, GUI svn.r4720)
;
_audit_update_record
;
2017-01-19 deposited with the CCDC.
2017-02-14 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 98.026(6)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   5.4583(3)
_cell_length_b                   10.3960(6)
_cell_length_c                   19.0896(10)
_cell_measurement_reflns_used    1552
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      25.1230
_cell_measurement_theta_min      3.7660
_cell_volume                     1072.62(10)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_collection
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CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2008)'
_computing_structure_solution    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_temperature      293.15
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.0874
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      0.0018138000
_diffrn_orient_matrix_UB_12      0.0652200000
_diffrn_orient_matrix_UB_13      -0.0107598000
_diffrn_orient_matrix_UB_21      -0.0051538000
_diffrn_orient_matrix_UB_22      -0.0198536000
_diffrn_orient_matrix_UB_23      -0.0357329000
_diffrn_orient_matrix_UB_31      -0.1311549000
_diffrn_orient_matrix_UB_32      0.0016804000
_diffrn_orient_matrix_UB_33      -0.0039256000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0183
_diffrn_reflns_av_unetI/netI     0.0474
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            4677
_diffrn_reflns_point_group_measured_fraction_full 0.803
_diffrn_reflns_point_group_measured_fraction_max 0.790
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.364
_diffrn_reflns_theta_min         3.233
_diffrn_source                   'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.073
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.67295
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_density_diffrn    1.169
_exptl_crystal_description       block
_exptl_crystal_F_000             408
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.2
_refine_diff_density_max         0.376
_refine_diff_density_min         -0.162
_refine_diff_density_rms         0.033
_refine_ls_abs_structure_details
;
 Flack x determined using 710 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   2.0(10)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.054
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     260
_refine_ls_number_reflns         3453
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.054
_refine_ls_R_factor_all          0.0727
_refine_ls_R_factor_gt           0.0509
_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^)+(0.0468P)^2^+0.1173P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1075
_refine_ls_wR_factor_ref         0.1217
_reflns_Friedel_coverage         0.497
_reflns_Friedel_fraction_full    0.584
_reflns_Friedel_fraction_max     0.557
_reflns_number_gt                2577
_reflns_number_total             3453
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm7b00254_si_004.cif
_cod_data_source_block           141229_s1_wsl_m
_cod_depositor_comments          'Adding full bibliography for 1545900.cif.'
_cod_original_cell_volume        1072.60(10)
_cod_database_code               1545900
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   0.986
_shelx_estimated_absorpt_t_min   0.978
_reflns_odcompleteness_completeness 99.78
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_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 C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C16(H16), C19(H19), C22(H22), C24(H24)
2.b Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), C9(H9A,H9B), C17(H17A,H17B), C18(H18A,H18B)
2.c Aromatic/amide H refined with riding coordinates:
 C1(H1), C2(H2), C3(H3), C4(H4), C6(H6), C10(H10), C14(H14), C15(H15), N1(H1A)
2.d Idealised Me refined as rotating group:
 C20(H20A,H20B,H20C), C21(H21A,H21B,H21C), C25(H25A,H25B,H25C)
;
_shelx_res_checksum              40765
_shelx_hkl_checksum              41606