Small-molecule phosphodiesterase probes: discovery of potent and selective CNS-penetrable quinazoline inhibitors of PDE1
Humphrey, John M.; Yang, Eddie; Ende, Christopher W. am; Arnold, Eric P.; Head, Jenna L.; Jenkinson, Stephen; Lebel, Lorraine A.; Liras, Spiros; Pandit, Jayvardhan; Samas, Brian; Vajdos, Felix; Simons, Samuel P.; Evdokimov, Artem; Mansour, Mahmoud; Menniti, Frank S.; MedChemComm 5 (2014) 1290–; doi:10.1039/C4MD00113C

data_7113303
_publ_section_title
;
 Small-molecule phosphodiesterase probes: discovery of potent and
 selective CNS-penetrable quinazoline inhibitors of PDE1
;
_journal_issue                   9
_journal_name_full               MedChemComm
_journal_page_first              1290
_journal_paper_doi               10.1039/C4MD00113C
_journal_volume                  5
_journal_year                    2014
_chemical_absolute_configuration ad
_chemical_formula_sum            'C19 H17 Cl N2 O2'
_chemical_formula_weight         340.80
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 95.024(2)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   7.3534(3)
_cell_length_b                   25.5994(8)
_cell_length_c                   9.1479(3)
_cell_measurement_reflns_used    2374
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      53.37
_cell_measurement_theta_min      3.45
_cell_volume                     1715.41(10)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 2008)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 2008)'
_diffrn_ambient_temperature      298(2)
_diffrn_measured_fraction_theta_full 0.975
_diffrn_measured_fraction_theta_max 0.975
_diffrn_measurement_device_type  'Bruker APEX'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0248
_diffrn_reflns_av_sigmaI/netI    0.0383
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       21
_diffrn_reflns_limit_k_min       -26
_diffrn_reflns_limit_l_max       9
_diffrn_reflns_limit_l_min       -9
_diffrn_reflns_number            7617
_diffrn_reflns_theta_full        54.35
_diffrn_reflns_theta_max         54.35
_diffrn_reflns_theta_min         3.45
_exptl_absorpt_coefficient_mu    2.078
_exptl_absorpt_correction_T_max  0.7457
_exptl_absorpt_correction_T_min  0.6694
_exptl_absorpt_correction_type   empirical
_exptl_absorpt_process_details   SADABS
_exptl_crystal_density_diffrn    1.320
_exptl_crystal_density_method    'not measured'
_exptl_crystal_F_000             712
_exptl_crystal_size_max          0.21
_exptl_crystal_size_mid          0.20
_exptl_crystal_size_min          0.15
_refine_diff_density_max         0.247
_refine_diff_density_min         -0.196
_refine_diff_density_rms         0.043
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.01(3)
_refine_ls_extinction_coef       0.0031(7)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     SHELXL
_refine_ls_goodness_of_fit_ref   1.122
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     438
_refine_ls_number_reflns         3195
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.122
_refine_ls_R_factor_all          0.0617
_refine_ls_R_factor_gt           0.0502
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.1107P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1445
_refine_ls_wR_factor_ref         0.1637
_reflns_number_gt                2650
_reflns_number_total             3195
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            c4md00113c2.cif
_cod_data_source_block           z153
_cod_depositor_comments
;
The following automatic conversions were performed:

'_symmetry_cell_setting' value 'Monoclinic' changed to 'monoclinic'
according to
/usr/data/users/saulius/crontab/automatic-downloads/rss-feeds/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 

 Adding full bibliography for 7113303.cif.
;
_cod_original_sg_symbol_H-M      P2(1)
_cod_database_code               7113303