data_A1H5U
# 
_chem_comp.id                                    A1H5U 
_chem_comp.name                                  "(5aSa,17aRa)- 20-Chloro-2-[(2S,5R)-2,5-dimethyl-4-(prop-2-enoyl)piperazin-1-yl]-14,17-difluoro-6-(propan-2-yl)-11,12-dihydro-4H-1,18-(ethanediylidene)pyrido[4,3-e]pyrimido[1,6-g][1,4,7,9]benzodioxadiazacyclododecin-4-one" 
_chem_comp.type                                  non-polymer 
_chem_comp.pdbx_type                             HETAIN 
_chem_comp.formula                               "C32 H33 Cl F2 N6 O4" 
_chem_comp.mon_nstd_parent_comp_id               ? 
_chem_comp.pdbx_synonyms                         "HYDROXYETHYLAMINE BACE INHIBITOR" 
_chem_comp.pdbx_formal_charge                    0 
_chem_comp.pdbx_initial_date                     2024-03-07 
_chem_comp.pdbx_modified_date                    2024-09-27 
_chem_comp.pdbx_ambiguous_flag                   N 
_chem_comp.pdbx_release_status                   REL 
_chem_comp.pdbx_replaced_by                      ? 
_chem_comp.pdbx_replaces                         ? 
_chem_comp.formula_weight                        639.092 
_chem_comp.one_letter_code                       ? 
_chem_comp.three_letter_code                     A1H5U 
_chem_comp.pdbx_model_coordinates_details        ? 
_chem_comp.pdbx_model_coordinates_missing_flag   N 
_chem_comp.pdbx_ideal_coordinates_details        Corina 
_chem_comp.pdbx_ideal_coordinates_missing_flag   N 
_chem_comp.pdbx_model_coordinates_db_code        8S8C 
_chem_comp.pdbx_subcomponent_list                ? 
_chem_comp.pdbx_processing_site                  PDBE 
_chem_comp.pdbx_pcm                              Y 
# 
loop_
_chem_comp_atom.comp_id 
_chem_comp_atom.atom_id 
_chem_comp_atom.alt_atom_id 
_chem_comp_atom.type_symbol 
_chem_comp_atom.charge 
_chem_comp_atom.pdbx_align 
_chem_comp_atom.pdbx_aromatic_flag 
_chem_comp_atom.pdbx_leaving_atom_flag 
_chem_comp_atom.pdbx_stereo_config 
_chem_comp_atom.pdbx_n_terminal_atom_flag 
_chem_comp_atom.pdbx_backbone_atom_flag 
_chem_comp_atom.pdbx_c_terminal_atom_flag 
_chem_comp_atom.model_Cartn_x 
_chem_comp_atom.model_Cartn_y 
_chem_comp_atom.model_Cartn_z 
_chem_comp_atom.pdbx_model_Cartn_x_ideal 
_chem_comp_atom.pdbx_model_Cartn_y_ideal 
_chem_comp_atom.pdbx_model_Cartn_z_ideal 
_chem_comp_atom.pdbx_component_atom_id 
_chem_comp_atom.pdbx_component_comp_id 
_chem_comp_atom.pdbx_ordinal 
A1H5U C1   C1  C  0 1 N N N N N N -12.450 -0.454 -20.024 -0.064 5.650  -0.410 C1   A1H5U 1  
A1H5U C2   C2  C  0 1 N N N N N N -13.356 0.743  -19.749 0.287  4.291  -1.018 C2   A1H5U 2  
A1H5U C3   C3  C  0 1 N N N N N N -13.954 1.266  -21.050 0.278  4.397  -2.545 C3   A1H5U 3  
A1H5U C6   C4  C  0 1 Y N N N N N -16.032 -1.150 -18.067 3.915  4.356  -0.565 C6   A1H5U 4  
A1H5U C7   C5  C  0 1 Y N N N N N -16.549 -0.307 -17.103 4.214  3.149  0.031  C7   A1H5U 5  
A1H5U C8   C6  C  0 1 Y N N N N N -15.990 0.958  -16.993 3.184  2.295  0.405  C8   A1H5U 6  
A1H5U O9   O1  O  0 1 N N N N N N -16.384 1.917  -16.090 3.454  1.096  0.968  O9   A1H5U 7  
A1H5U C10  C7  C  0 1 N N N N N N -17.710 1.852  -15.523 4.808  0.744  1.245  C10  A1H5U 8  
A1H5U C11  C8  C  0 1 N N N N N N -18.768 2.072  -16.577 5.303  -0.237 0.179  C11  A1H5U 9  
A1H5U C13  C9  C  0 1 Y N N N N N -19.352 3.792  -18.156 3.905  -2.080 -0.334 C13  A1H5U 10 
A1H5U C14  C10 C  0 1 Y N N N N N -20.668 3.539  -18.511 4.927  -3.021 -0.421 C14  A1H5U 11 
A1H5U C16  C11 C  0 1 Y N N N N N -21.159 3.864  -19.755 4.689  -4.357 -0.159 C16  A1H5U 12 
A1H5U C21  C12 C  0 1 Y N N N N N -17.089 4.655  -18.670 1.455  -1.555 -0.119 C21  A1H5U 13 
A1H5U C23  C13 C  0 1 Y N N N N N -15.093 3.761  -18.031 0.632  0.557  0.334  C23  A1H5U 14 
A1H5U C25  C14 C  0 1 Y N N N N N -14.944 1.317  -17.852 1.860  2.693  0.172  C25  A1H5U 15 
A1H5U C26  C15 C  0 1 N N N N N N -13.110 2.737  -17.077 -0.205 2.546  1.250  C26  A1H5U 16 
A1H5U C31  C16 C  0 1 N N N N N N -11.329 6.392  -16.481 -3.405 -0.912 1.217  C31  A1H5U 17 
A1H5U C36  C17 C  0 1 N N N N N N -11.172 7.688  -19.079 -4.971 0.755  -0.660 C36  A1H5U 18 
A1H5U C37  C18 C  0 1 N N S N N N -12.508 7.272  -18.491 -4.162 1.387  0.480  C37  A1H5U 19 
A1H5U C39  C19 C  0 1 N N N N N N -13.134 8.467  -17.781 -3.573 2.720  0.014  C39  A1H5U 20 
A1H5U C40  C20 C  0 1 N N N N N N -9.546  9.116  -17.979 -6.586 -1.050 -0.284 C40  A1H5U 21 
A1H5U O41  O2  O  0 1 N N N N N N -9.903  10.031 -18.705 -6.859 -2.164 0.111  O41  A1H5U 22 
A1H5U C42  C21 C  0 1 N N N N N N -8.366  9.290  -17.044 -7.680 -0.135 -0.772 C42  A1H5U 23 
A1H5U C43  C22 C  0 1 N N N N N N -7.331  10.251 -17.604 -9.029 -0.849 -0.664 C43  A1H5U 24 
A1H5U N35  N1  N  0 1 N N N N N N -10.204 7.932  -18.005 -5.306 -0.631 -0.287 N35  A1H5U 25 
A1H5U N30  N2  N  0 1 N N N N N N -12.284 6.149  -17.561 -3.073 0.470  0.847  N30  A1H5U 26 
A1H5U C32  C23 C  0 1 N N R N N N -9.989  6.820  -17.059 -4.216 -1.547 0.080  C32  A1H5U 27 
A1H5U C34  C24 C  0 1 N N N N N N -9.303  5.648  -17.735 -4.803 -2.880 0.550  C34  A1H5U 28 
A1H5U C29  C25 C  0 1 N N N N N N -13.091 5.033  -17.491 -1.774 0.897  0.844  C29  A1H5U 29 
A1H5U N28  N3  N  0 1 N N N N N N -12.499 3.949  -17.006 -1.449 2.096  1.303  N28  A1H5U 30 
A1H5U O27  O3  O  0 1 N N N N N N -12.628 1.726  -16.575 0.082  3.557  1.871  O27  A1H5U 31 
A1H5U N24  N4  N  0 1 N N S N N N -14.346 2.633  -17.754 0.775  1.899  0.550  N24  A1H5U 32 
A1H5U C4   C26 C  0 1 Y N N N N N -14.483 0.398  -18.800 1.656  3.870  -0.552 C4   A1H5U 33 
A1H5U N5   N5  N  0 1 Y N N N N N -15.029 -0.823 -18.899 2.668  4.663  -0.847 N5   A1H5U 34 
A1H5U O12  O4  O  0 1 N N N N N N -18.829 3.476  -16.909 4.183  -0.768 -0.537 O12  A1H5U 35 
A1H5U F15  F1  F  0 1 N N N N N N -21.486 2.955  -17.604 6.173  -2.625 -0.757 F15  A1H5U 36 
A1H5U C17  C27 C  0 1 Y N N N N N -20.315 4.461  -20.677 3.416  -4.763 0.199  C17  A1H5U 37 
A1H5U C18  C28 C  0 1 Y N N N N N -19.010 4.712  -20.322 2.380  -3.847 0.263  C18  A1H5U 38 
A1H5U F19  F2  F  0 1 N N N N N N -18.188 5.297  -21.229 1.186  -4.271 0.731  F19  A1H5U 39 
A1H5U C20  C29 C  0 1 Y N N N N N -18.494 4.392  -19.074 2.593  -2.502 -0.067 C20  A1H5U 40 
A1H5U N22  N6  N  0 1 Y N N N N N -16.357 3.568  -18.400 1.645  -0.268 0.139  N22  A1H5U 41 
A1H5U C44  C30 C  0 1 Y N N N N N -14.480 5.015  -17.906 -0.684 0.038  0.359  C44  A1H5U 42 
A1H5U C45  C31 C  0 1 Y N N N N N -15.260 6.122  -18.189 -0.926 -1.270 -0.070 C45  A1H5U 43 
A1H5U C46  C32 C  0 1 Y N N N N N -16.570 5.930  -18.572 0.166  -2.046 -0.345 C46  A1H5U 44 
A1H5U CL47 CL1 CL 0 0 N N N N N N -17.516 7.331  -18.918 -0.088 -3.604 -1.070 CL47 A1H5U 45 
A1H5U H49  H1  H  0 1 N N N N N N -12.027 -0.819 -19.077 0.671  6.390  -0.727 H49  A1H5U 46 
A1H5U H50  H2  H  0 1 N N N N N N -13.036 -1.256 -20.497 -1.055 5.955  -0.748 H50  A1H5U 47 
A1H5U H48  H3  H  0 1 N N N N N N -11.635 -0.150 -20.697 -0.058 5.574  0.677  H48  A1H5U 48 
A1H5U H51  H4  H  0 1 N N N N N N -12.750 1.542  -19.298 -0.449 3.551  -0.702 H51  A1H5U 49 
A1H5U H52  H5  H  0 1 N N N N N N -14.604 2.127  -20.835 1.013  5.137  -2.861 H52  A1H5U 50 
A1H5U H53  H6  H  0 1 N N N N N N -13.144 1.577  -21.727 0.528  3.429  -2.978 H53  A1H5U 51 
A1H5U H54  H7  H  0 1 N N N N N N -14.545 0.471  -21.527 -0.712 4.702  -2.882 H54  A1H5U 52 
A1H5U H55  H8  H  0 1 N N N N N N -16.462 -2.137 -18.158 4.710  5.039  -0.823 H55  A1H5U 53 
A1H5U H56  H9  H  0 1 N N N N N N -17.358 -0.621 -16.459 5.252  2.893  0.180  H56  A1H5U 54 
A1H5U H58  H10 H  0 1 N N N N N N -17.808 2.628  -14.750 5.456  1.623  1.269  H58  A1H5U 55 
A1H5U H57  H11 H  0 1 N N N N N N -17.857 0.861  -15.069 4.869  0.267  2.229  H57  A1H5U 56 
A1H5U H60  H12 H  0 1 N N N N N N -19.744 1.743  -16.191 5.971  0.277  -0.512 H60  A1H5U 57 
A1H5U H59  H13 H  0 1 N N N N N N -18.515 1.493  -17.477 5.848  -1.050 0.669  H59  A1H5U 58 
A1H5U H61  H14 H  0 1 N N N N N N -22.188 3.656  -20.009 5.492  -5.074 -0.231 H61  A1H5U 59 
A1H5U H63  H15 H  0 1 N N N N N N -11.714 7.187  -15.826 -2.488 -1.480 1.373  H63  A1H5U 60 
A1H5U H64  H16 H  0 1 N N N N N N -11.196 5.469  -15.898 -3.996 -0.914 2.133  H64  A1H5U 61 
A1H5U H68  H17 H  0 1 N N N N N N -10.797 6.887  -19.732 -5.887 1.323  -0.817 H68  A1H5U 62 
A1H5U H69  H18 H  0 1 N N N N N N -11.304 8.609  -19.666 -4.377 0.755  -1.574 H69  A1H5U 63 
A1H5U H38  H19 H  0 1 N N N N N N -13.174 6.950  -19.305 -4.810 1.553  1.340  H38  A1H5U 64 
A1H5U H72  H20 H  0 1 N N N N N N -14.103 8.173  -17.352 -4.367 3.343  -0.398 H72  A1H5U 65 
A1H5U H70  H21 H  0 1 N N N N N N -12.465 8.807  -16.977 -3.114 3.230  0.861  H70  A1H5U 66 
A1H5U H71  H22 H  0 1 N N N N N N -13.285 9.284  -18.502 -2.820 2.537  -0.752 H71  A1H5U 67 
A1H5U H77  H23 H  0 1 N N N N N N -8.730  9.681  -16.082 -7.697 0.768  -0.162 H77  A1H5U 68 
A1H5U H73  H24 H  0 1 N N N N N N -7.891  8.310  -16.885 -7.493 0.133  -1.812 H73  A1H5U 69 
A1H5U H1   H25 H  0 1 N N N N N N -6.496  10.346 -16.894 -9.011 -1.752 -1.275 H1   A1H5U 70 
A1H5U H74  H26 H  0 1 N N N N N N -6.955  9.866  -18.563 -9.216 -1.117 0.376  H74  A1H5U 71 
A1H5U H75  H27 H  0 1 N N N N N N -7.793  11.237 -17.760 -9.819 -0.187 -1.017 H75  A1H5U 72 
A1H5U H33  H28 H  0 1 N N N N N N -9.350  7.169  -16.234 -3.571 -1.712 -0.782 H33  A1H5U 73 
A1H5U H65  H29 H  0 1 N N N N N N -9.157  4.837  -17.006 -5.355 -3.342 -0.268 H65  A1H5U 74 
A1H5U H66  H30 H  0 1 N N N N N N -9.928  5.286  -18.565 -3.996 -3.541 0.863  H66  A1H5U 75 
A1H5U H67  H31 H  0 1 N N N N N N -8.326  5.970  -18.125 -5.476 -2.705 1.389  H67  A1H5U 76 
A1H5U H62  H32 H  0 1 N N N N N N -20.676 4.725  -21.660 3.226  -5.801 0.426  H62  A1H5U 77 
A1H5U H76  H33 H  0 1 N N N N N N -14.850 7.118  -18.111 -1.924 -1.675 -0.138 H76  A1H5U 78 
# 
loop_
_chem_comp_bond.comp_id 
_chem_comp_bond.atom_id_1 
_chem_comp_bond.atom_id_2 
_chem_comp_bond.value_order 
_chem_comp_bond.pdbx_aromatic_flag 
_chem_comp_bond.pdbx_stereo_config 
_chem_comp_bond.pdbx_ordinal 
A1H5U F19  C18 SING N N 1  
A1H5U C3   C2  SING N N 2  
A1H5U C17  C18 DOUB Y N 3  
A1H5U C17  C16 SING Y N 4  
A1H5U C18  C20 SING Y N 5  
A1H5U C1   C2  SING N N 6  
A1H5U C16  C14 DOUB Y N 7  
A1H5U C2   C4  SING N N 8  
A1H5U C36  C37 SING N N 9  
A1H5U C36  N35 SING N N 10 
A1H5U C20  C21 SING N N 11 
A1H5U C20  C13 DOUB Y N 12 
A1H5U CL47 C46 SING N N 13 
A1H5U N5   C4  DOUB Y N 14 
A1H5U N5   C6  SING Y N 15 
A1H5U C4   C25 SING Y N 16 
A1H5U O41  C40 DOUB N N 17 
A1H5U C21  C46 DOUB Y N 18 
A1H5U C21  N22 SING Y N 19 
A1H5U C46  C45 SING Y N 20 
A1H5U C14  C13 SING Y N 21 
A1H5U C14  F15 SING N N 22 
A1H5U C37  C39 SING N N 23 
A1H5U C37  N30 SING N N 24 
A1H5U N22  C23 DOUB Y N 25 
A1H5U C45  C44 DOUB Y N 26 
A1H5U C13  O12 SING N N 27 
A1H5U C6   C7  DOUB Y N 28 
A1H5U C23  C44 SING Y N 29 
A1H5U C23  N24 SING N N 30 
A1H5U N35  C40 SING N N 31 
A1H5U N35  C32 SING N N 32 
A1H5U C40  C42 SING N N 33 
A1H5U C44  C29 SING N N 34 
A1H5U C25  N24 SING N N 35 
A1H5U C25  C8  DOUB Y N 36 
A1H5U N24  C26 SING N N 37 
A1H5U C34  C32 SING N N 38 
A1H5U C43  C42 SING N N 39 
A1H5U N30  C29 SING N N 40 
A1H5U N30  C31 SING N N 41 
A1H5U C29  N28 DOUB N N 42 
A1H5U C7   C8  SING Y N 43 
A1H5U C26  N28 SING N N 44 
A1H5U C26  O27 DOUB N N 45 
A1H5U C32  C31 SING N N 46 
A1H5U C8   O9  SING N N 47 
A1H5U O12  C11 SING N N 48 
A1H5U C11  C10 SING N N 49 
A1H5U O9   C10 SING N N 50 
A1H5U C1   H49 SING N N 51 
A1H5U C1   H50 SING N N 52 
A1H5U C1   H48 SING N N 53 
A1H5U C2   H51 SING N N 54 
A1H5U C3   H52 SING N N 55 
A1H5U C3   H53 SING N N 56 
A1H5U C3   H54 SING N N 57 
A1H5U C6   H55 SING N N 58 
A1H5U C7   H56 SING N N 59 
A1H5U C10  H58 SING N N 60 
A1H5U C10  H57 SING N N 61 
A1H5U C11  H60 SING N N 62 
A1H5U C11  H59 SING N N 63 
A1H5U C16  H61 SING N N 64 
A1H5U C31  H63 SING N N 65 
A1H5U C31  H64 SING N N 66 
A1H5U C36  H68 SING N N 67 
A1H5U C36  H69 SING N N 68 
A1H5U C37  H38 SING N N 69 
A1H5U C39  H72 SING N N 70 
A1H5U C39  H70 SING N N 71 
A1H5U C39  H71 SING N N 72 
A1H5U C42  H77 SING N N 73 
A1H5U C42  H73 SING N N 74 
A1H5U C43  H1  SING N N 75 
A1H5U C43  H74 SING N N 76 
A1H5U C43  H75 SING N N 77 
A1H5U C32  H33 SING N N 78 
A1H5U C34  H65 SING N N 79 
A1H5U C34  H66 SING N N 80 
A1H5U C34  H67 SING N N 81 
A1H5U C17  H62 SING N N 82 
A1H5U C45  H76 SING N N 83 
# 
loop_
_pdbx_chem_comp_descriptor.comp_id 
_pdbx_chem_comp_descriptor.type 
_pdbx_chem_comp_descriptor.program 
_pdbx_chem_comp_descriptor.program_version 
_pdbx_chem_comp_descriptor.descriptor 
A1H5U InChI            InChI                1.06  "InChI=1S/C32H33ClF2N6O4/c1-6-24(42)39-14-18(5)40(15-17(39)4)30-19-13-20(33)27-25-21(34)7-8-22(35)29(25)45-12-11-44-23-9-10-36-26(16(2)3)28(23)41(31(19)37-27)32(43)38-30/h7-10,13,16-18H,6,11-12,14-15H2,1-5H3/t17-,18+/m1/s1" 
A1H5U InChIKey         InChI                1.06  ZCLGGAMHRVYGDO-MSOLQXFVSA-N                                                                                                                                                                                                     
A1H5U SMILES_CANONICAL CACTVS               3.385 "CCC(=O)N1C[C@H](C)N(C[C@H]1C)C2=NC(=O)[N@@]3c4nc(c(Cl)cc24)c5c(F)ccc(F)c5OCCOc6ccnc(C(C)C)c36"                                                                                                                                 
A1H5U SMILES           CACTVS               3.385 "CCC(=O)N1C[CH](C)N(C[CH]1C)C2=NC(=O)[N]3c4nc(c(Cl)cc24)c5c(F)ccc(F)c5OCCOc6ccnc(C(C)C)c36"                                                                                                                                     
A1H5U SMILES_CANONICAL "OpenEye OEToolkits" 2.0.7 "CCC(=O)N1C[C@@H](N(C[C@H]1C)C2=NC(=O)N3c4c(ccnc4C(C)C)OCCOc5c(ccc(c5-c6c(cc2c3n6)Cl)F)F)C"                                                                                                                                     
A1H5U SMILES           "OpenEye OEToolkits" 2.0.7 "CCC(=O)N1CC(N(CC1C)C2=NC(=O)N3c4c(ccnc4C(C)C)OCCOc5c(ccc(c5-c6c(cc2c3n6)Cl)F)F)C"                                                                                                                                              
# 
loop_
_pdbx_chem_comp_audit.comp_id 
_pdbx_chem_comp_audit.action_type 
_pdbx_chem_comp_audit.date 
_pdbx_chem_comp_audit.processing_site 
A1H5U "Create component" 2024-03-07 PDBE 
A1H5U "Modify name"      2024-03-31 PDBE 
A1H5U "Initial release"  2024-07-10 RCSB 
A1H5U "Modify PCM"       2024-09-27 PDBE 
# 
_pdbx_chem_comp_pcm.pcm_id                             1 
_pdbx_chem_comp_pcm.comp_id                            A1H5U 
_pdbx_chem_comp_pcm.modified_residue_id                CYS 
_pdbx_chem_comp_pcm.type                               None 
_pdbx_chem_comp_pcm.category                           "Covalent chemical modification" 
_pdbx_chem_comp_pcm.position                           "Amino-acid side chain" 
_pdbx_chem_comp_pcm.polypeptide_position               "Any position" 
_pdbx_chem_comp_pcm.comp_id_linking_atom               C43 
_pdbx_chem_comp_pcm.modified_residue_id_linking_atom   SG 
_pdbx_chem_comp_pcm.uniprot_specific_ptm_accession     ? 
_pdbx_chem_comp_pcm.uniprot_generic_ptm_accession      ? 
# 
