Identification and optimisation of 3,3-dimethyl-azetidin-2-ones as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
McCoull, William; Augustin, Martin; Blake, Caroline; Ertan, Anne; Kilgour, Elaine; Krapp, Stephan; Moore, Jane E.; Newcombe, Nicholas J.; Packer, Martin J.; Rees, Amanda; Revill, John; Scott, James S.; Selmi, Nidhal; Gerhardt, Stefan; Ogg, Derek J.; Steinbacher, Stefan; Whittamore, Paul R. O.; MedChemComm 5 (2014) 57–; doi:10.1039/c3md00234a

data_7112106
_publ_section_title
;
 Identification and optimisation of 3,3-dimethyl-azetidin-2-ones as potent
 and selective inhibitors of 11\b-hydroxysteroid dehydrogenase type 1
 (11\b-HSD1)
;
_journal_issue                   1
_journal_name_full               MedChemComm
_journal_page_first              57
_journal_paper_doi               10.1039/c3md00234a
_journal_volume                  5
_journal_year                    2014
_chemical_absolute_configuration ad
_chemical_compound_source
;Laboratory at AlderleyPark Ba 001 isomer 2, crystallised from diethyl
ether by evaporation
;
_chemical_formula_moiety         'C18 H18 Br N O2'
_chemical_formula_sum            'C18 H18 Br N O2'
_chemical_formula_weight         360.23
_chemical_name_common            ' AZ12576722, AZ SBBG: 2006-10-306'
_chemical_name_systematic
;
(4R)-4-(4-bromophenyl)-1-(4-methoxyphenyl)-3,3-dimethylazetidin-2-one
;
_space_group_IT_number           19
_symmetry_cell_setting           orthorhombic
_symmetry_Int_Tables_number      19
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_audit_creation_method           'maXus and PLATON'
_cell_angle_alpha                90.00
_cell_angle_beta                 90.00
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   5.9750(2)
_cell_length_b                   11.6900(3)
_cell_length_c                   23.7850(5)
_cell_measurement_reflns_used    19607
_cell_measurement_temperature    200
_cell_measurement_theta_max      27.485
_cell_measurement_theta_min      1.018
_cell_volume                     1661.33(8)
_computing_cell_refinement       'DENZO-SMN (Otwinowski & Minor, 1997)'
_computing_data_collection       'KappaCCD Software (Nonius, 2000)'
_computing_data_reduction
'DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997)'
_computing_molecular_graphics
;
ORTEPII (Johnson, 1976), PLATON (Spek, 2003)
;
_computing_publication_material  'PLATON (Spek, 2003)'
_computing_structure_refinement  'SHELXL97 (Sheldrick, 1997)'
_computing_structure_solution    'SIR97 (Altomare et al., 1999)'
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_device       KappaCCD
_diffrn_measurement_method       CCD
_diffrn_orient_matrix_type       X=UH
_diffrn_orient_matrix_UB_11      0.01461
_diffrn_orient_matrix_UB_12      -0.08277
_diffrn_orient_matrix_UB_13      0.00996
_diffrn_orient_matrix_UB_21      -0.13305
_diffrn_orient_matrix_UB_22      0.00648
_diffrn_orient_matrix_UB_23      0.02531
_diffrn_orient_matrix_UB_31      -0.10047
_diffrn_orient_matrix_UB_32      -0.02061
_diffrn_orient_matrix_UB_33      -0.03206
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           ' MoK\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_radiation_wavelength_id  all
_diffrn_reflns_av_R_equivalents  0.0572
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       30
_diffrn_reflns_limit_l_min       -30
_diffrn_reflns_number            3815
_diffrn_reflns_theta_full        27.48
_diffrn_reflns_theta_max         27.48
_diffrn_reflns_theta_min         1.71
_exptl_absorpt_coefficient_mu    2.481
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            Colourless
_exptl_crystal_density_diffrn    1.440
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       Rod
_exptl_crystal_F_000             736
_exptl_crystal_size_max          0.40
_exptl_crystal_size_mid          0.10
_exptl_crystal_size_min          0.04
_refine_diff_density_max         0.487
_refine_diff_density_min         -0.506
_refine_diff_density_rms         0.056
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.007(9)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.054
_refine_ls_hydrogen_treatment    refU
_refine_ls_matrix_type           full
_refine_ls_number_parameters     199
_refine_ls_number_reflns         3788
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.054
_refine_ls_R_factor_all          0.0549
_refine_ls_R_factor_gt           0.0370
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0537P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0883
_refine_ls_wR_factor_ref         0.0941
_reflns_number_gt                2938
_reflns_number_total             3788
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            c3md00234a.txt
_cod_data_source_block           AZ12576722
_cod_depositor_comments
;
The following automatic conversions were performed:

'_symmetry_cell_setting' value 'Orthorhombic' changed to
'orthorhombic' according to
/usr/data/users/saulius/automatic-downloads/current/RSC/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 from 2011-04-26.

Automatic conversion script
Id: cif_fix_values 2281 2013-09-26 08:29:07Z andrius 
;
_cod_database_code               7112106