Discovery of N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl]-5-methyl-1H-pyrazole-3-carboxamide (MK-5596) as a novel cannabinoid-1 receptor (CB1R) inverse agonist for the treatment of obesity.
Yan, Lin; Huo, Pei; Debenham, John S.; Madsen-Duggan, Christina B; Lao, Julie; Chen, Richard Z.; Xiao, Jing Chen; Shen, Chun-Pyn; Stribling, D. Sloan; Shearman, Lauren P.; Strack, Alison M.; Tsou, Nancy; Ball, Richard G.; Wang, Junying; Tong, Xinchun; Bateman, Thomas J.; Reddy, Vijay B. G.; Fong, Tung M.; Hale, Jeffrey J.; Journal of medicinal chemistry 53 (2010) 4028–4037; doi:10.1021/jm100023j

data_1502658
_publ_section_title
;
 Discovery of
 N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl]-5-methyl-1H-pyrazole-3-carboxamide
 (MK-5596) as a novel cannabinoid-1 receptor (CB1R) inverse agonist for
 the treatment of obesity.
;
_journal_issue                   10
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              4028
_journal_page_last               4037
_journal_paper_doi               10.1021/jm100023j
_journal_volume                  53
_journal_year                    2010
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C27 H23 Cl3 N4 O2'
_chemical_formula_sum            'C27 H23 Cl3 N4 O2'
_chemical_formula_weight         541.84
_space_group_IT_number           19
_symmetry_cell_setting           orthorhombic
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_audit_creation_date             2010-01-06
_audit_creation_method           'cif4actac using yanl1107a.cif'
_cell_angle_alpha                90.
_cell_angle_beta                 90.
_cell_angle_gamma                90.
_cell_formula_units_Z            4
_cell_length_a                   11.1695(8)
_cell_length_b                   11.2252(8)
_cell_length_c                   20.0044(14)
_cell_measurement_reflns_used    9949
_cell_measurement_temperature    100
_cell_measurement_theta_max      28.46
_cell_measurement_theta_min      2.57
_cell_volume                     2508.1(3)
_computing_cell_refinement       'SAINT V7.34A'
_computing_data_collection       'SAINT V7.34A'
_computing_data_reduction        'SAINT V7.34A'
_computing_molecular_graphics
;
ORTEP3 (Johnson,2000), PLATON (Spek,1990),
PSPLUTO (local version of Motherwell's program)
;
_computing_publication_material  'locally developed programs'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      100
_diffrn_detector                 CCD
_diffrn_detector_area_resol_mean 8.333
_diffrn_detector_type            'Bruker APEXII'
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'Bruker PLATFORM'
_diffrn_measurement_method       'omega, phi oscillation scans'
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.045
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       26
_diffrn_reflns_limit_l_min       -26
_diffrn_reflns_number            34470
_diffrn_reflns_theta_full        28.64
_diffrn_reflns_theta_max         28.64
_exptl_absorpt_coefficient_mu    0.4
_exptl_absorpt_correction_T_max  0.965
_exptl_absorpt_correction_T_min  0.837
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
;
_exptl_crystal_colour            translucent
_exptl_crystal_density_diffrn    1.435
_exptl_crystal_density_method    none
_exptl_crystal_description       block
_exptl_crystal_F_000             1120
_exptl_crystal_size_max          0.28
_exptl_crystal_size_mid          0.17
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.29
_refine_diff_density_min         -0.35
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.02(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.174
_refine_ls_hydrogen_treatment    constr
_refine_ls_number_parameters     322
_refine_ls_number_reflns         6426
_refine_ls_restrained_S_all      1.18
_refine_ls_R_factor_gt           0.043
_refine_ls_shift/su_max          0.01
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0227P)^2^+2.2001P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.090
_refine_ls_wR_factor_ref         0.096
_reflns_number_gt                5500
_reflns_number_total             6426
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jm100023j_si_002.cif
_cod_data_source_block           yanl1107a
_cod_depositor_comments
;
The following automatic conversions were performed:

'_symmetry_cell_setting' value 'Orthorhombic' changed to
'orthorhombic' according to
/home/saulius/struct/CIF-dictionaries/cif_core.dic dictionary named
'cif_core.dic' version 2.4.2 from 2011-04-26.

Automatic conversion script
Id: cif_fix_values 1715 2011-07-08 13:25:40Z adriana 
;
_cod_database_code               1502658