Discovery and Preclinical Characterization of the Cyclopropylindolobenzazepine BMS-791325, A Potent Allosteric Inhibitor of the Hepatitis C Virus NS5B Polymerase.
Gentles, Robert G.; Ding, Min; Bender, John A.; Bergstrom, Carl P.; Grant-Young, Katharine; Hewawasam, Piyasena; Hudyma, Thomas; Martin, Scott; Nickel, Andrew; Regueiro-Ren, Alicia; Tu, Yong; Yang, Zhong; Yeung, Kap-Sun; Zheng, Xiaofan; Chao, Sam; Sun, Jung-Hui; Beno, Brett R.; Camac, Daniel M.; Chang, Chong-Hwan; Gao, Mian; Morin, Paul E.; Sheriff, Steven; Tredup, Jeff; Wan, John; Witmer, Mark R.; Xie, Dianlin; Hanumegowda, Umesh; Knipe, Jay; Mosure, Kathy; Santone, Kenneth S.; Parker, Dawn D.; Zhuo, Xiaoliang; Lemm, Julie; Liu, Mengping; Pelosi, Lenore; Rigat, Karen; Voss, Stacey; Wang, Yi; Wang, Ying-Kai; Colonno, Richard J.; Gao, Min; Roberts, Susan B.; Gao, Qi; Ng, Alicia; Meanwell, Nicholas A.; Kadow, John F.; Journal of medicinal chemistry 57 (2014) 1855–1879; doi:10.1021/jm4016894

data_1513802
_publ_contact_author             'Alicia Ng, Qi Gao'
_publ_section_title
;
 Discovery and Preclinical Characterization of the
 Cyclopropylindolobenzazepine BMS-791325, A Potent Allosteric Inhibitor of
 the Hepatitis C Virus NS5B Polymerase.
;
_journal_issue                   5
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              1855
_journal_page_last               1879
_journal_paper_doi               10.1021/jm4016894
_journal_volume                  57
_journal_year                    2014
_chemical_formula_sum            'C36 H46 Cl N5 O6 S'
_chemical_formula_weight         712.29
_chemical_name_common            BMS-791325
_chemical_name_systematic
; 
 (4bS,5aR)-12-cyclohexyl-N-(N,N-dimethylsulfamoyl)-3-methoxy-5a-((1R,5S)-3-methyl-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)
 -4b,5,5a,6-tetrahydrobenzo[3,4]cyclopropa[5,6]azepino[1,2-a]indole-9-carboxamide 
;
_space_group_IT_number           5
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  'C 2y'
_symmetry_space_group_name_H-M   'C 1 2 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                 90.761(2)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   28.0870(13)
_cell_length_b                   11.9998(6)
_cell_length_c                   10.9846(6)
_cell_measurement_reflns_used    4143
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      27.485
_cell_measurement_theta_min      0.998
_cell_volume                     3701.9(3)
_computing_cell_refinement       'HKL Scalepack (Otwinowski & Minor 1997)'
_computing_data_collection       'SuperGUI Collect (Bruker AXS BV, 1997-2004)'
_computing_data_reduction
'HKL Denzo and Scalepack (Otwinowski & Minor 1997)'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      293(2)
_diffrn_detector_area_resol_mean 9
_diffrn_measured_fraction_theta_full 0.991
_diffrn_measured_fraction_theta_max 0.991
_diffrn_measurement_device_type  KappaCCD
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0000
_diffrn_reflns_av_sigmaI/netI    0.0772
_diffrn_reflns_limit_h_max       36
_diffrn_reflns_limit_h_min       -36
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            7006
_diffrn_reflns_theta_full        27.42
_diffrn_reflns_theta_max         27.42
_diffrn_reflns_theta_min         2.37
_exptl_absorpt_coefficient_mu    0.210
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.278
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       blade
_exptl_crystal_F_000             1512
_exptl_crystal_size_max          0.265
_exptl_crystal_size_mid          0.088
_exptl_crystal_size_min          0.018
_refine_diff_density_max         0.645
_refine_diff_density_min         -0.432
_refine_diff_density_rms         0.155
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.00(9)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.110
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     451
_refine_ls_number_reflns         7006
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.110
_refine_ls_R_factor_all          0.1184
_refine_ls_R_factor_gt           0.0709
_refine_ls_shift/su_max          0.010
_refine_ls_shift/su_mean         0.001
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.1000P)^2^+1.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1723
_refine_ls_wR_factor_ref         0.2065
_reflns_number_gt                4633
_reflns_number_total             7006
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jm4016894_si_002.cif
_cod_data_source_block           BMS-791325
_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/current/ACS/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_original_sg_symbol_H-M      C2
_cod_database_code               1513802