JP2008534552A - 血栓症治療用の新規な医薬組成物 - Google Patents
血栓症治療用の新規な医薬組成物 Download PDFInfo
- Publication number
- JP2008534552A JP2008534552A JP2008503489A JP2008503489A JP2008534552A JP 2008534552 A JP2008534552 A JP 2008534552A JP 2008503489 A JP2008503489 A JP 2008503489A JP 2008503489 A JP2008503489 A JP 2008503489A JP 2008534552 A JP2008534552 A JP 2008534552A
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- pharmaceutical composition
- carbonyl
- composition according
- patients
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 79
- 208000007536 Thrombosis Diseases 0.000 title claims abstract description 15
- -1 antiplatelet agent Substances 0.000 claims abstract description 91
- 239000004480 active ingredient Substances 0.000 claims abstract description 86
- 150000001875 compounds Chemical class 0.000 claims abstract description 44
- 229940123900 Direct thrombin inhibitor Drugs 0.000 claims abstract description 39
- 239000003868 thrombin inhibitor Substances 0.000 claims abstract description 39
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 21
- 108010014173 Factor X Proteins 0.000 claims abstract description 19
- 229940127218 antiplatelet drug Drugs 0.000 claims abstract description 19
- 239000003112 inhibitor Substances 0.000 claims abstract description 19
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 19
- 239000002319 fibrinogen receptor antagonist Substances 0.000 claims abstract description 14
- 229920000669 heparin Polymers 0.000 claims abstract description 14
- 239000003055 low molecular weight heparin Substances 0.000 claims abstract description 14
- 229940127215 low-molecular weight heparin Drugs 0.000 claims abstract description 14
- 229940019333 vitamin k antagonists Drugs 0.000 claims abstract description 14
- 108090000288 Glycoproteins Proteins 0.000 claims abstract description 13
- 102000003886 Glycoproteins Human genes 0.000 claims abstract description 13
- 239000005557 antagonist Substances 0.000 claims abstract description 13
- 108090000190 Thrombin Proteins 0.000 claims abstract description 12
- 239000003698 antivitamin K Substances 0.000 claims abstract description 12
- 239000003937 drug carrier Substances 0.000 claims abstract description 12
- 229960004072 thrombin Drugs 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 9
- 229920001499 Heparinoid Polymers 0.000 claims abstract description 8
- 239000002554 heparinoid Substances 0.000 claims abstract description 8
- 229940025770 heparinoids Drugs 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 47
- 239000002253 acid Substances 0.000 claims description 30
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 21
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 claims description 17
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 claims description 17
- 238000009472 formulation Methods 0.000 claims description 16
- 229960003009 clopidogrel Drugs 0.000 claims description 15
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 14
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 12
- 206010047249 Venous thrombosis Diseases 0.000 claims description 12
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 11
- 229940125782 compound 2 Drugs 0.000 claims description 10
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 9
- 238000007887 coronary angioplasty Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 208000010125 myocardial infarction Diseases 0.000 claims description 9
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical group C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 claims description 9
- 150000004677 hydrates Chemical class 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 8
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 229960005001 ticlopidine Drugs 0.000 claims description 7
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 claims description 7
- 239000000106 platelet aggregation inhibitor Substances 0.000 claims description 6
- 230000009861 stroke prevention Effects 0.000 claims description 6
- 238000001356 surgical procedure Methods 0.000 claims description 6
- 230000002537 thrombolytic effect Effects 0.000 claims description 6
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 208000001435 Thromboembolism Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 3
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 3
- 206010052895 Coronary artery insufficiency Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 210000004351 coronary vessel Anatomy 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000000399 orthopedic effect Effects 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 230000001732 thrombotic effect Effects 0.000 claims description 3
- 229960001522 ximelagatran Drugs 0.000 claims description 3
- ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 claims description 3
- CDPROXZBMHOBTQ-SJORKVTESA-N 2-[[(2r)-3-cyclohexyl-1-[(2s)-2-[3-(diaminomethylideneamino)propylcarbamoyl]piperidin-1-yl]-1-oxopropan-2-yl]amino]acetic acid Chemical compound NC(N)=NCCCNC(=O)[C@@H]1CCCCN1C(=O)[C@H](NCC(O)=O)CC1CCCCC1 CDPROXZBMHOBTQ-SJORKVTESA-N 0.000 claims description 2
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 claims description 2
- 102000007625 Hirudins Human genes 0.000 claims description 2
- 108010007267 Hirudins Proteins 0.000 claims description 2
- 229960003856 argatroban Drugs 0.000 claims description 2
- KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 claims description 2
- 229960003850 dabigatran Drugs 0.000 claims description 2
- YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 claims description 2
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical group CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 claims description 2
- 239000002628 heparin derivative Substances 0.000 claims description 2
- 229940006607 hirudin Drugs 0.000 claims description 2
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 claims description 2
- 229950003291 inogatran Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229960002137 melagatran Drugs 0.000 claims description 2
- DKWNMCUOEDMMIN-PKOBYXMFSA-N melagatran Chemical compound C1=CC(C(=N)N)=CC=C1CNC(=O)[C@H]1N(C(=O)[C@H](NCC(O)=O)C2CCCCC2)CC1 DKWNMCUOEDMMIN-PKOBYXMFSA-N 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 description 26
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 239000003826 tablet Substances 0.000 description 14
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
- 229940098779 methanesulfonic acid Drugs 0.000 description 7
- 235000021317 phosphate Nutrition 0.000 description 7
- YMZJXUFDWISWOF-RVQJUJIASA-N 4-[(2s)-2-(aminomethyl)pyrrolidine-1-carbonyl]-3-chloro-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfinylpropyl]benzamide Chemical compound N([C@@H](CCS(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CCC[C@H]1CN YMZJXUFDWISWOF-RVQJUJIASA-N 0.000 description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 6
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 6
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- 239000001530 fumaric acid Substances 0.000 description 5
- 239000011976 maleic acid Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- RSGDQMKQVSAEMO-JOCHJYFZSA-N 4-[acetyl(cyclopentyl)amino]-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methylsulfanylethyl]-3-methylbenzamide Chemical compound N([C@H](CSC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1C)=CC=C1N(C(C)=O)C1CCCC1 RSGDQMKQVSAEMO-JOCHJYFZSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- XGBHUMKSNKSZNX-AWEZNQCLSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]-6-methylquinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2C)=NC=NC1=CC=2C(=O)N1CCCC1 XGBHUMKSNKSZNX-AWEZNQCLSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 150000007514 bases Chemical class 0.000 description 4
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 125000001841 imino group Chemical group [H]N=* 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- RUHMXJKQXZYSIF-UHFFFAOYSA-N n-[(6-chloro-1h-benzimidazol-2-yl)-phenylmethyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)NC(C=2NC3=CC=C(Cl)C=C3N=2)C=2C=CC=CC=2)=CC=C1C(=O)N1CCCC1 RUHMXJKQXZYSIF-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000011975 tartaric acid Substances 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- AZKQDXOHILUHFD-IBGZPJMESA-N 3-chloro-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)butyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](CCC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CC=CC1 AZKQDXOHILUHFD-IBGZPJMESA-N 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 description 3
- CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 3
- 108010056764 Eptifibatide Proteins 0.000 description 3
- 229940123583 Factor Xa inhibitor Drugs 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- WQUXFWRNMWSHNO-NSHDSACASA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]-(1,3-thiazolidin-3-yl)methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCSC1 WQUXFWRNMWSHNO-NSHDSACASA-N 0.000 description 3
- 150000001447 alkali salts Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229960000610 enoxaparin Drugs 0.000 description 3
- CZKPOZZJODAYPZ-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CNC2=CC=CC=C12 CZKPOZZJODAYPZ-LROMGURASA-N 0.000 description 3
- 229960001318 fondaparinux Drugs 0.000 description 3
- 229960002897 heparin Drugs 0.000 description 3
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 3
- MVPQUSQUURLQKF-MCPDASDXSA-E nonasodium;(2s,3s,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3s,4s,5r,6r)-2-carboxylato-4,5-dimethoxy-6-[(2r,3r,4s,5r,6s)-6-methoxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-di Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]S(=O)(=O)O[C@@H]1[C@@H](OS([O-])(=O)=O)[C@@H](OC)O[C@H](COS([O-])(=O)=O)[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@@H]2[C@@H]([C@@H](OS([O-])(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](OC)[C@H](O[C@@H]4[C@@H]([C@@H](OC)[C@H](OC)[C@@H](COS([O-])(=O)=O)O4)OC)[C@H](O3)C([O-])=O)OC)[C@@H](COS([O-])(=O)=O)O2)OS([O-])(=O)=O)[C@H](C([O-])=O)O1 MVPQUSQUURLQKF-MCPDASDXSA-E 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 description 3
- QKLXBIHSGMPUQS-FGZHOGPDSA-M (3r,5r)-7-[4-(4-fluorophenyl)-2,5-dimethyl-1-phenylpyrrol-3-yl]-3,5-dihydroxyheptanoate Chemical compound CC1=C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C(C)N1C1=CC=CC=C1 QKLXBIHSGMPUQS-FGZHOGPDSA-M 0.000 description 2
- QRDAPCMJAOQZSU-KQQUZDAGSA-N (e)-3-[4-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-n-hydroxyprop-2-enamide Chemical compound C1=C(\C=C\C(=O)NO)N(C)C=C1\C=C\C(=O)C1=CC=CC(F)=C1 QRDAPCMJAOQZSU-KQQUZDAGSA-N 0.000 description 2
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 2
- OFJRNBWSFXEHSA-UHFFFAOYSA-N 2-(3-amino-1,2-benzoxazol-5-yl)-n-[4-[2-[(dimethylamino)methyl]imidazol-1-yl]-2-fluorophenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide Chemical compound CN(C)CC1=NC=CN1C(C=C1F)=CC=C1NC(=O)C1=CC(C(F)(F)F)=NN1C1=CC=C(ON=C2N)C2=C1 OFJRNBWSFXEHSA-UHFFFAOYSA-N 0.000 description 2
- YRGZMEPXUSMUPP-IBGZPJMESA-N 3-bromo-n-[(1r)-1-(6-bromo-1h-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](COC)C=1NC2=CC=C(Br)C=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CC=CC1 YRGZMEPXUSMUPP-IBGZPJMESA-N 0.000 description 2
- OLZCOZYOACSGTK-FQEVSTJZSA-N 3-bromo-n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-ethoxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](COCC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CC=CC1 OLZCOZYOACSGTK-FQEVSTJZSA-N 0.000 description 2
- LAQZRUWNSGYVHD-SFHVURJKSA-N 3-bromo-n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](CO)C=1NC2=CC(Cl)=CC=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CC=CC1 LAQZRUWNSGYVHD-SFHVURJKSA-N 0.000 description 2
- OWCDPSYVKRORHI-IBGZPJMESA-N 3-bromo-n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CC=CC1 OWCDPSYVKRORHI-IBGZPJMESA-N 0.000 description 2
- DTXZRUBEKPVFBE-IBGZPJMESA-N 3-bromo-n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N([C@@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CCCC1 DTXZRUBEKPVFBE-IBGZPJMESA-N 0.000 description 2
- INEYFUQRZLZMFK-NRFANRHFSA-N 3-bromo-n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-prop-2-ynoxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](COCC#C)C=1NC2=CC=C(C=C2N=1)Cl)C(=O)C(C=C1Br)=CC=C1C(=O)N1CC=CC1 INEYFUQRZLZMFK-NRFANRHFSA-N 0.000 description 2
- SDSMXMSJNZGOBX-IBGZPJMESA-N 3-bromo-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CCCC1 SDSMXMSJNZGOBX-IBGZPJMESA-N 0.000 description 2
- YLPSLOPYNLABCA-IBGZPJMESA-N 3-bromo-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)butyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](CCC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CC=CC1 YLPSLOPYNLABCA-IBGZPJMESA-N 0.000 description 2
- OTTTUQHZIIULLI-IBGZPJMESA-N 3-chloro-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CCCC1 OTTTUQHZIIULLI-IBGZPJMESA-N 0.000 description 2
- RWTQYKUONPWEES-UHFFFAOYSA-N 3-chloro-n-[(6-chloro-1h-benzimidazol-2-yl)methyl]-4-(3-oxopiperazine-1-carbonyl)benzamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1CNC(=O)C(C=C1Cl)=CC=C1C(=O)N1CCNC(=O)C1 RWTQYKUONPWEES-UHFFFAOYSA-N 0.000 description 2
- NNJFWSBCDMTQGX-UHFFFAOYSA-N 3-chloro-n-[1-(6-chloro-1h-benzimidazol-2-yl)ethyl]-4-(2-pyridin-3-ylpiperidine-1-carbonyl)benzamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(=O)C(C=C1Cl)=CC=C1C(=O)N1CCCCC1C1=CC=CN=C1 NNJFWSBCDMTQGX-UHFFFAOYSA-N 0.000 description 2
- GDIKJXXZRARNKX-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n,n-diethylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)N(CC)CC)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 GDIKJXXZRARNKX-UHFFFAOYSA-N 0.000 description 2
- KPCJCGWQNRDYHS-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(2,2,2-trifluoroethyl)butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCC(F)(F)F)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 KPCJCGWQNRDYHS-UHFFFAOYSA-N 0.000 description 2
- HGWPBTGFBUCYDA-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(2-hydroxyethyl)butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCCO)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 HGWPBTGFBUCYDA-UHFFFAOYSA-N 0.000 description 2
- FZMLWCDQELFMQZ-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(cyclopropylmethyl)-n-methylbutanamide Chemical compound N=1C=NC2=CC(C(=O)N3CCCC3)=C(Cl)C=C2C=1NC(C=1NC2=CC=C(Cl)C=C2N=1)CCC(=O)N(C)CC1CC1 FZMLWCDQELFMQZ-UHFFFAOYSA-N 0.000 description 2
- KJAZZYOZBPUDLE-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-[2-(dimethylamino)ethyl]-n-methylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)N(C)CCN(C)C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 KJAZZYOZBPUDLE-UHFFFAOYSA-N 0.000 description 2
- LOWSCQHGSZHIIX-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-[2-(dimethylamino)ethyl]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCCN(C)C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 LOWSCQHGSZHIIX-UHFFFAOYSA-N 0.000 description 2
- DIZXLHIFUIUOOK-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-[2-(pyridin-4-ylamino)ethyl]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NCCNC1=CC=NC=C1 DIZXLHIFUIUOOK-UHFFFAOYSA-N 0.000 description 2
- YZFGINMRXMWMOP-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-cyclopropyl-n-methylbutanamide Chemical compound N=1C=NC2=CC(C(=O)N3CCCC3)=C(Cl)C=C2C=1NC(C=1NC2=CC=C(Cl)C=C2N=1)CCC(=O)N(C)C1CC1 YZFGINMRXMWMOP-UHFFFAOYSA-N 0.000 description 2
- ABKGUPQLWXSSEY-JXFKEZNVSA-N 4-[(2s)-2-(aminomethyl)pyrrolidine-1-carbonyl]-3-chloro-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]benzamide Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CCC[C@H]1CN ABKGUPQLWXSSEY-JXFKEZNVSA-N 0.000 description 2
- GMJOOPRTIOBJQC-JXFKEZNVSA-N 4-[(2s)-2-(aminomethyl)pyrrolidine-1-carbonyl]-3-chloro-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]benzamide Chemical compound N([C@@H](CCS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CCC[C@H]1CN GMJOOPRTIOBJQC-JXFKEZNVSA-N 0.000 description 2
- SOTDRXSXFFOMDO-JXFKEZNVSA-N 4-[(2s)-2-(aminomethyl)pyrrolidine-1-carbonyl]-3-chloro-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)butyl]benzamide Chemical compound N([C@@H](CCC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CCC[C@H]1CN SOTDRXSXFFOMDO-JXFKEZNVSA-N 0.000 description 2
- SSVFRHRXPVMKDZ-UHFFFAOYSA-N 4-[2-(aminomethyl)pyrrolidine-1-carbonyl]-3-chloro-n-[1-(6-chloro-1h-benzimidazol-2-yl)ethyl]benzamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(=O)C(C=C1Cl)=CC=C1C(=O)N1CCCC1CN SSVFRHRXPVMKDZ-UHFFFAOYSA-N 0.000 description 2
- GZERKQHTAMDCGI-UHFFFAOYSA-N 4-[4-[[1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]-6-methylquinoline-7-carbonyl]piperazin-2-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCSC)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCNC(=O)C1 GZERKQHTAMDCGI-UHFFFAOYSA-N 0.000 description 2
- FFXMMUQJKCFJLO-GOSISDBHSA-N 4-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]amino]quinazoline-7-carbonyl]piperazin-2-one Chemical compound N([C@H](CO)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCNC(=O)C1 FFXMMUQJKCFJLO-GOSISDBHSA-N 0.000 description 2
- NKLOLMQJDLMZRE-UHFFFAOYSA-N 6-chloro-1h-benzimidazole Chemical compound ClC1=CC=C2N=CNC2=C1 NKLOLMQJDLMZRE-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229940122388 Thrombin inhibitor Drugs 0.000 description 2
- XANBDYJRXBRKPJ-ZUOKHONESA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]amino]quinazolin-7-yl]methanone Chemical compound NC[C@H]1CCCN1C(=O)C1=CC2=NC=NC(N[C@H](CO)C=3NC4=CC=C(Cl)C=C4N=3)=C2C=C1Cl XANBDYJRXBRKPJ-ZUOKHONESA-N 0.000 description 2
- XAHSRTFNRQVPDW-QRWLVFNGSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CN XAHSRTFNRQVPDW-QRWLVFNGSA-N 0.000 description 2
- CPVNKLWRHQRGFJ-QBYSONFBSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfinylpropyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](CCS(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CN CPVNKLWRHQRGFJ-QBYSONFBSA-N 0.000 description 2
- HPHBHDUSVYOGTD-QRWLVFNGSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](CCS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CN HPHBHDUSVYOGTD-QRWLVFNGSA-N 0.000 description 2
- YLMSXNRSXYNMJV-GXTWGEPZSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CN YLMSXNRSXYNMJV-GXTWGEPZSA-N 0.000 description 2
- HGNBKXMAULMPKA-BEUBQONESA-N [(2r)-2-[amino(methylsulfonyl)methyl]pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](CCS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1C(N)S(C)(=O)=O HGNBKXMAULMPKA-BEUBQONESA-N 0.000 description 2
- GWOSHEGHIBUWTR-UHFFFAOYSA-N [4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]-6-methylquinolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCCC1 GWOSHEGHIBUWTR-UHFFFAOYSA-N 0.000 description 2
- RXMKXQLMQHESMK-UHFFFAOYSA-N [4-[[1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]amino]-6-methylquinolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound CC1=CC2=C(NC(CCS(C)(=O)=O)C=3NC4=CC=C(Cl)C=C4N=3)C=CN=C2C=C1C(=O)N1CCCC1 RXMKXQLMQHESMK-UHFFFAOYSA-N 0.000 description 2
- NZRCKCNDRZSXHM-ZZWBGTBQSA-N [6-bromo-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-(1,3-thiazolidin-2-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Br)=NC=NC1=CC=2C(=O)C1NCCS1 NZRCKCNDRZSXHM-ZZWBGTBQSA-N 0.000 description 2
- YPHYCHLMZNDYID-HXUWFJFHSA-N [6-bromo-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Br)=NC=NC1=CC=2C(=O)N1CC=CC1 YPHYCHLMZNDYID-HXUWFJFHSA-N 0.000 description 2
- IKMZDHWOYWYJTR-LBPRGKRZSA-N [6-bromo-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Br)=NC=NC1=CC=2C(=O)N1CC=CC1 IKMZDHWOYWYJTR-LBPRGKRZSA-N 0.000 description 2
- RFWYAAZYBLYSRF-LJQANCHMSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](CO)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 RFWYAAZYBLYSRF-LJQANCHMSA-N 0.000 description 2
- KRFFCDITXHDYGG-ZZWBGTBQSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-(1,3-thiazolidin-2-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)C1NCCS1 KRFFCDITXHDYGG-ZZWBGTBQSA-N 0.000 description 2
- BCFWJMYQBDXGNR-HXUWFJFHSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 BCFWJMYQBDXGNR-HXUWFJFHSA-N 0.000 description 2
- CGVLJASAIJQWHX-NRFANRHFSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-(1,1-dioxo-1,2-thiazolidin-2-yl)propyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound C([C@@H](C=1NC2=CC=C(C=C2N=1)Cl)NC=1C2=CC(Cl)=C(C(=O)N3CC=CC3)C=C2N=CN=1)CN1CCCS1(=O)=O CGVLJASAIJQWHX-NRFANRHFSA-N 0.000 description 2
- ZNQCCBMUUWWSSS-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methoxypropyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCOC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 ZNQCCBMUUWWSSS-IBGZPJMESA-N 0.000 description 2
- RQHGXOYKVGDQRP-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 RQHGXOYKVGDQRP-IBGZPJMESA-N 0.000 description 2
- YIXULUKTIICPNC-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 YIXULUKTIICPNC-IBGZPJMESA-N 0.000 description 2
- ZBLDZSBGMXPXNY-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]amino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@@H](CCS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 ZBLDZSBGMXPXNY-IBGZPJMESA-N 0.000 description 2
- PULJCUHABQICCL-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)butyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 PULJCUHABQICCL-IBGZPJMESA-N 0.000 description 2
- KRKQMWHVCXTIFN-LBPRGKRZSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 KRKQMWHVCXTIFN-LBPRGKRZSA-N 0.000 description 2
- WLYWOHREUVJHNO-LBPRGKRZSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 WLYWOHREUVJHNO-LBPRGKRZSA-N 0.000 description 2
- 229960000446 abciximab Drugs 0.000 description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229960004676 antithrombotic agent Drugs 0.000 description 2
- 229960003886 apixaban Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- 229940077388 benzenesulfonate Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- TVRYMMKZRZBXBH-VWLOTQADSA-N benzyl (4s)-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoate Chemical compound C([C@@H](C=1NC2=CC=C(C=C2N=1)Cl)NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CC(=O)OCC1=CC=CC=C1 TVRYMMKZRZBXBH-VWLOTQADSA-N 0.000 description 2
- JGFDYOPPLIVQLL-NDEPHWFRSA-N benzyl n-[(5s)-5-(6-chloro-1h-benzimidazol-2-yl)-5-[[3-methyl-4-(pyrrolidine-1-carbonyl)benzoyl]amino]pentyl]carbamate Chemical compound CC1=CC(C(=O)N[C@@H](CCCCNC(=O)OCC=2C=CC=CC=2)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 JGFDYOPPLIVQLL-NDEPHWFRSA-N 0.000 description 2
- 239000007963 capsule composition Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229960004969 dalteparin Drugs 0.000 description 2
- 229960003828 danaparoid Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229960004468 eptifibatide Drugs 0.000 description 2
- NYFXIFORCJEPCK-FQEVSTJZSA-N ethyl (4s)-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(2,5-dihydropyrrole-1-carbonyl)quinazolin-4-yl]amino]butanoate Chemical compound N([C@@H](CCC(=O)OCC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 NYFXIFORCJEPCK-FQEVSTJZSA-N 0.000 description 2
- VXLJQDPUTFXYCN-FQEVSTJZSA-N ethyl (4s)-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoate Chemical compound N([C@@H](CCC(=O)OCC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 VXLJQDPUTFXYCN-FQEVSTJZSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- FYVOJJBMSQFAOF-SFHVURJKSA-N n-[(1r)-1-(6-bromo-1h-benzimidazol-2-yl)-2-hydroxyethyl]-3-chloro-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](CO)C=1NC2=CC=C(Br)C=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CC=CC1 FYVOJJBMSQFAOF-SFHVURJKSA-N 0.000 description 2
- KQORXQUOVZHIOJ-IBGZPJMESA-N n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CO)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 KQORXQUOVZHIOJ-IBGZPJMESA-N 0.000 description 2
- ZEOBBQISYXVYKH-SFHVURJKSA-N n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)-3-(trifluoromethyl)benzamide Chemical compound N([C@@H](CO)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1C(F)(F)F)=CC=C1C(=O)N1CC=CC1 ZEOBBQISYXVYKH-SFHVURJKSA-N 0.000 description 2
- FLGOVBBBTRHNGA-IBGZPJMESA-N n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)-3-methylbenzamide Chemical compound CC1=CC(C(=O)N[C@@H](CO)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CC=CC1 FLGOVBBBTRHNGA-IBGZPJMESA-N 0.000 description 2
- NYFNPJJDRQUKJO-FQEVSTJZSA-N n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N([C@@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1C)=CC=C1C(=O)N1CCCC1 NYFNPJJDRQUKJO-FQEVSTJZSA-N 0.000 description 2
- KZNIQEYEHQCMOE-FQEVSTJZSA-N n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)-3-methylbenzamide Chemical compound N([C@@H](COC)C=1NC2=CC(Cl)=CC=C2N=1)C(=O)C(C=C1C)=CC=C1C(=O)N1CC=CC1 KZNIQEYEHQCMOE-FQEVSTJZSA-N 0.000 description 2
- VYNKVNDKAOGAAQ-RUZDIDTESA-N n-[(1r)-2-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-2-oxo-1-phenylethyl]-1h-indole-6-carboxamide Chemical compound C1CN(C)CCC1N1CCN(C(=O)[C@H](NC(=O)C=2C=C3NC=CC3=CC=2)C=2C=CC=CC=2)CC1 VYNKVNDKAOGAAQ-RUZDIDTESA-N 0.000 description 2
- AWGAMXJCLLDCOD-DEOSSOPVSA-N n-[(1s)-1,3-bis(6-chloro-1h-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCC=2NC3=CC=C(Cl)C=C3N=2)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 AWGAMXJCLLDCOD-DEOSSOPVSA-N 0.000 description 2
- NEHQHBCRPPTITC-NRFANRHFSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-(2-chloroethylcarbamoylamino)propyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCNC(=O)NCCCl)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 NEHQHBCRPPTITC-NRFANRHFSA-N 0.000 description 2
- BZCJAJYUJWMEPM-FQEVSTJZSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-(methanesulfonamido)propyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCNS(C)(=O)=O)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 BZCJAJYUJWMEPM-FQEVSTJZSA-N 0.000 description 2
- GIQKVPRDYSGSEQ-FQEVSTJZSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-(methanesulfonamido)propyl]-4-(2,5-dihydropyrrole-1-carbonyl)-3-methylbenzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCNS(C)(=O)=O)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CC=CC1 GIQKVPRDYSGSEQ-FQEVSTJZSA-N 0.000 description 2
- ZJDHCLWEPVKIFP-FQEVSTJZSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1C)=CC=C1C(=O)N1CCCC1 ZJDHCLWEPVKIFP-FQEVSTJZSA-N 0.000 description 2
- JEIHYYUQOHXSSV-VWLOTQADSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-4-(2-methyl-2,6-diazaspiro[3.4]octan-6-yl)-4-oxobutyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound C1N(C)CC21CN(C(=O)CC[C@H](NC(=O)C=1C=C(C)C(C(=O)N3CCCC3)=CC=1)C=1NC3=CC=C(Cl)C=C3N=1)CC2 JEIHYYUQOHXSSV-VWLOTQADSA-N 0.000 description 2
- HOXXPKVCSSRJCX-QPPBQGQZSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-4-[(2r)-2-(hydroxymethyl)pyrrolidin-1-yl]-4-oxobutyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCC(=O)N2[C@H](CCC2)CO)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 HOXXPKVCSSRJCX-QPPBQGQZSA-N 0.000 description 2
- MOJCALZXKCDURL-QHCPKHFHSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-4-oxo-4-pyrrolidin-1-ylbutyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCC(=O)N2CCCC2)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 MOJCALZXKCDURL-QHCPKHFHSA-N 0.000 description 2
- MHMWIAUKLJQIKY-FQEVSTJZSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)butyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N([C@@H](CCC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1C)=CC=C1C(=O)N1CCCC1 MHMWIAUKLJQIKY-FQEVSTJZSA-N 0.000 description 2
- YNYDJAGWMFXYQN-FQEVSTJZSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)butyl]-4-(2,5-dihydropyrrole-1-carbonyl)-3-methylbenzamide Chemical compound N([C@@H](CCC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1C)=CC=C1C(=O)N1CC=CC1 YNYDJAGWMFXYQN-FQEVSTJZSA-N 0.000 description 2
- ZPAAUQXGKGQYEY-URXFXBBRSA-N n-[(1s)-4-[(2s)-2-(aminomethyl)pyrrolidin-1-yl]-1-(6-chloro-1h-benzimidazol-2-yl)-4-oxobutyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCC(=O)N2[C@@H](CCC2)CN)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 ZPAAUQXGKGQYEY-URXFXBBRSA-N 0.000 description 2
- WNCGGHURWVEGHN-IBGZPJMESA-N n-[(3s)-3-(6-chloro-1h-benzimidazol-2-yl)-3-[[6-chloro-7-(2,5-dihydropyrrole-1-carbonyl)quinazolin-4-yl]amino]propyl]methanesulfonamide Chemical compound N([C@@H](CCNS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 WNCGGHURWVEGHN-IBGZPJMESA-N 0.000 description 2
- AQKCVIJGQHMSEJ-UHFFFAOYSA-N n-[1-(6-bromo-1h-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N=1C2=CC(Br)=CC=C2NC=1C(C)NC(=O)C(C=C1C)=CC=C1C(=O)N1CCCC1 AQKCVIJGQHMSEJ-UHFFFAOYSA-N 0.000 description 2
- NYFNPJJDRQUKJO-UHFFFAOYSA-N n-[1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(COC)NC(=O)C(C=C1C)=CC=C1C(=O)N1CCCC1 NYFNPJJDRQUKJO-UHFFFAOYSA-N 0.000 description 2
- XSXSXHGFTUXHHS-UHFFFAOYSA-N n-[1-(6-chloro-1h-benzimidazol-2-yl)ethyl]-3-ethyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CCC1=CC(C(=O)NC(C)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 XSXSXHGFTUXHHS-UHFFFAOYSA-N 0.000 description 2
- CVUIHKMGZPCPKV-UHFFFAOYSA-N n-[[1-(6-chloro-1h-benzimidazol-2-yl)cyclohexa-2,4-dien-1-yl]methyl]-4-(2,5-dihydropyrrole-1-carbonyl)-3-methylbenzamide Chemical compound CC1=CC(C(=O)NCC2(C=CC=CC2)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CC=CC1 CVUIHKMGZPCPKV-UHFFFAOYSA-N 0.000 description 2
- XNCLAXZMCGEFKA-UHFFFAOYSA-N n-benzyl-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NCC1=CC=CC=C1 XNCLAXZMCGEFKA-UHFFFAOYSA-N 0.000 description 2
- 229960000899 nadroparin Drugs 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- DQDAYGNAKTZFIW-UHFFFAOYSA-N phenprocoumon Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC)C1=CC=CC=C1 DQDAYGNAKTZFIW-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- OUMVYGWUYKOJFH-UVMFRMCBSA-N tert-butyl (2R)-2-(aminomethyl)-1-[(4S)-4-(6-chloro-1H-benzimidazol-2-yl)-4-[[3-methyl-4-(pyrrolidine-1-carbonyl)benzoyl]amino]butanoyl]pyrrolidine-2-carboxylate Chemical compound ClC1=CC2=C(NC(=N2)[C@H](CCC(=O)N2[C@@](CCC2)(C(=O)OC(C)(C)C)CN)NC(C2=CC(=C(C=C2)C(=O)N2CCCC2)C)=O)C=C1 OUMVYGWUYKOJFH-UVMFRMCBSA-N 0.000 description 2
- YXBBWNRAGIDXKC-QHCPKHFHSA-N tert-butyl 2-[(2r)-2-(6-chloro-1h-benzimidazol-2-yl)-2-[[3-methyl-4-(pyrrolidine-1-carbonyl)benzoyl]amino]ethoxy]acetate Chemical compound CC1=CC(C(=O)N[C@@H](COCC(=O)OC(C)(C)C)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 YXBBWNRAGIDXKC-QHCPKHFHSA-N 0.000 description 2
- RDMOQHCBQBXEBZ-CVDCTZTESA-N tert-butyl n-[[(2s)-1-[2-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]carbamoyl]benzoyl]pyrrolidin-2-yl]methyl]carbamate Chemical compound N([C@@H](CCSC)C=1NC2=CC(Cl)=CC=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CCC[C@H]1CNC(=O)OC(C)(C)C RDMOQHCBQBXEBZ-CVDCTZTESA-N 0.000 description 2
- 229960005062 tinzaparin Drugs 0.000 description 2
- 229960003425 tirofiban Drugs 0.000 description 2
- 229960005080 warfarin Drugs 0.000 description 2
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- OHHAYGMJNFSKNG-LIRRHRJNSA-N (4s)-4-[[7-[(2s)-2-(aminomethyl)pyrrolidine-1-carbonyl]-6-chloroquinazolin-4-yl]amino]-4-(6-chloro-1h-benzimidazol-2-yl)butanoic acid Chemical compound NC[C@@H]1CCCN1C(=O)C1=CC2=NC=NC(N[C@@H](CCC(O)=O)C=3NC4=CC=C(Cl)C=C4N=3)=C2C=C1Cl OHHAYGMJNFSKNG-LIRRHRJNSA-N 0.000 description 1
- DMJDEZUEYXVYNO-DHZHZOJOSA-N (e)-3-(4-phenylphenyl)prop-2-enoic acid Chemical compound C1=CC(/C=C/C(=O)O)=CC=C1C1=CC=CC=C1 DMJDEZUEYXVYNO-DHZHZOJOSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- DMDZXHOBZWZWMI-UHFFFAOYSA-N 2-(3-carbamimidoylphenyl)-2-methyl-n-[3-methyl-4-(pyrrolidine-1-carbonyl)phenyl]propanamide Chemical compound C=1C=C(C(=O)N2CCCC2)C(C)=CC=1NC(=O)C(C)(C)C1=CC=CC(C(N)=N)=C1 DMDZXHOBZWZWMI-UHFFFAOYSA-N 0.000 description 1
- ACFLXQIWOZPFDW-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-3-phenyl-N-[4-(pyrrolidine-1-carbonyl)-3-(trifluoromethyl)phenyl]propanamide Chemical compound NC(=N)C1=CC=C(O)C(C(CC=2C=CC=CC=2)C(=O)NC=2C=C(C(C(=O)N3CCCC3)=CC=2)C(F)(F)F)=C1 ACFLXQIWOZPFDW-UHFFFAOYSA-N 0.000 description 1
- WTPPUXIHAAIFEF-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[3-methyl-4-(pyrrolidine-1-carbonyl)phenyl]acetamide Chemical compound C=1C=C(C(=O)N2CCCC2)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O WTPPUXIHAAIFEF-UHFFFAOYSA-N 0.000 description 1
- LJWQJTBXKYHJEE-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[4-(pyrrolidine-1-carbonyl)-3-(trifluoromethyl)phenyl]propanamide Chemical compound C=1C(C(N)=N)=CC=C(O)C=1C(C)C(=O)NC(C=C1C(F)(F)F)=CC=C1C(=O)N1CCCC1 LJWQJTBXKYHJEE-UHFFFAOYSA-N 0.000 description 1
- MAOALPSHCIBFJZ-RUZDIDTESA-N 2-[[(2r)-2-[2-[[4-[amino(azaniumylidene)methyl]anilino]methyl]-1-methylbenzimidazol-5-yl]-1-oxo-1-pyrrolidin-1-ylpropan-2-yl]amino]acetate Chemical compound N=1C2=CC([C@@](C)(NCC(O)=O)C(=O)N3CCCC3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 MAOALPSHCIBFJZ-RUZDIDTESA-N 0.000 description 1
- ZHXGXULYUZVCBR-UHFFFAOYSA-N 2-[[2-[(4-carbamimidoylanilino)methyl]-1-methylbenzimidazol-5-yl]-quinolin-8-ylsulfonylamino]acetic acid Chemical compound N=1C2=CC(N(CC(O)=O)S(=O)(=O)C=3C4=NC=CC=C4C=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 ZHXGXULYUZVCBR-UHFFFAOYSA-N 0.000 description 1
- UDXBFVFGUYSOME-UHFFFAOYSA-N 2-[[2-[2-[(4-carbamimidoylanilino)methyl]-1-methylbenzimidazol-5-yl]-2-methyl-3-oxo-3-pyrrolidin-1-ylpropyl]amino]acetic acid Chemical compound N=1C2=CC(C(C)(CNCC(O)=O)C(=O)N3CCCC3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 UDXBFVFGUYSOME-UHFFFAOYSA-N 0.000 description 1
- BXXAXANRYAQUAM-UHFFFAOYSA-N 2-ethyl-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound C(C)C1=C(C(=O)N)C=CC(=C1C)C(=O)N1CCCC1 BXXAXANRYAQUAM-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZMPRRFPMMJQXPP-UHFFFAOYSA-N 2-sulfobenzoic acid Chemical class OC(=O)C1=CC=CC=C1S(O)(=O)=O ZMPRRFPMMJQXPP-UHFFFAOYSA-N 0.000 description 1
- GXCKBPZTXDIIHR-UHFFFAOYSA-N 3-(3-carbamimidoylphenyl)-3-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]propanoic acid Chemical compound NC(=N)C1=CC=CC(C(CC(O)=O)NC=2C3=CC(Cl)=C(C(=O)N4CCCC4)C=C3N=CN=2)=C1 GXCKBPZTXDIIHR-UHFFFAOYSA-N 0.000 description 1
- DMJDEZUEYXVYNO-UHFFFAOYSA-N 3-(4-phenylphenyl)prop-2-enoic acid Chemical compound C1=CC(C=CC(=O)O)=CC=C1C1=CC=CC=C1 DMJDEZUEYXVYNO-UHFFFAOYSA-N 0.000 description 1
- OUUHCFQNWCARFH-UHFFFAOYSA-N 3-[[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]methyl]-4-hydroxybenzenecarboximidamide Chemical compound NC(=N)C1=CC=C(O)C(CNC=2C3=CC(Cl)=C(C(=O)N4CCCC4)C=C3N=CN=2)=C1 OUUHCFQNWCARFH-UHFFFAOYSA-N 0.000 description 1
- WUGBZNHVMYDJSZ-SFHVURJKSA-N 3-bromo-n-[(1r)-1-(6-bromo-1h-benzimidazol-2-yl)-2-hydroxyethyl]-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N([C@@H](CO)C=1NC2=CC=C(Br)C=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CCCC1 WUGBZNHVMYDJSZ-SFHVURJKSA-N 0.000 description 1
- WYECXFDVPXRPKQ-IBGZPJMESA-N 3-bromo-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound N([C@@H](CCS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Br)=CC=C1C(=O)N1CCCC1 WYECXFDVPXRPKQ-IBGZPJMESA-N 0.000 description 1
- GVXOZSSQJWKTPN-SFHVURJKSA-N 3-chloro-n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](CO)C=1NC2=CC(Cl)=CC=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CC=CC1 GVXOZSSQJWKTPN-SFHVURJKSA-N 0.000 description 1
- PJHBCFOYSQUKEE-IBGZPJMESA-N 3-chloro-n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrole-1-carbonyl)benzamide Chemical compound N([C@@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1Cl)=CC=C1C(=O)N1CC=CC1 PJHBCFOYSQUKEE-IBGZPJMESA-N 0.000 description 1
- WGVMKLYIWWIIIX-QFBILLFUSA-N 3-chloro-n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]-4-[(2r)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]benzamide Chemical compound C([C@H]1CCCN1C(=O)C1=CC=C(C=C1Cl)C(=O)N[C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)N1CCCC1 WGVMKLYIWWIIIX-QFBILLFUSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ALKOINOBWCYBTA-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-methyl-n-[2-(methylamino)-2-oxoethyl]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)N(C)CC(=O)NC)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 ALKOINOBWCYBTA-UHFFFAOYSA-N 0.000 description 1
- MAGBCZBHOVIDJU-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-methyl-n-piperidin-4-ylbutanamide Chemical compound N=1C=NC2=CC(C(=O)N3CCCC3)=C(Cl)C=C2C=1NC(C=1NC2=CC(Cl)=CC=C2N=1)CCC(=O)N(C)C1CCNCC1 MAGBCZBHOVIDJU-UHFFFAOYSA-N 0.000 description 1
- WQZNLXOLFPLAMV-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-piperidin-4-ylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NC1CCNCC1 WQZNLXOLFPLAMV-UHFFFAOYSA-N 0.000 description 1
- DEJXXVQJMXTPLQ-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoic acid Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)O)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 DEJXXVQJMXTPLQ-UHFFFAOYSA-N 0.000 description 1
- ZWGRFVIVQYBHJY-UHFFFAOYSA-N 4-hydroxy-3-[2-phenyl-1-[[7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]ethyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=C(O)C(C(CC=2C=CC=CC=2)NC=2C3=CC=C(C=C3N=CN=2)C(=O)N2CCCC2)=C1 ZWGRFVIVQYBHJY-UHFFFAOYSA-N 0.000 description 1
- IJPMONDQLMWKGE-UHFFFAOYSA-N 4-hydroxy-3-[[[6-methyl-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]methyl]benzenecarboximidamide Chemical compound N1=CN=C2C=C(C(=O)N3CCCC3)C(C)=CC2=C1NCC1=CC(C(N)=N)=CC=C1O IJPMONDQLMWKGE-UHFFFAOYSA-N 0.000 description 1
- LEKPHEUTAHOLKA-UHFFFAOYSA-N 4-hydroxy-3-[[[7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]methyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=C(O)C(CNC=2C3=CC=C(C=C3N=CN=2)C(=O)N2CCCC2)=C1 LEKPHEUTAHOLKA-UHFFFAOYSA-N 0.000 description 1
- ZOTPACDGKSMJRN-UHFFFAOYSA-N 4-hydroxy-3-[[[7-methoxy-6-(pyrrolidine-1-carbonyl)isoquinolin-1-yl]amino]methyl]benzenecarboximidamide Chemical compound N1=CC=C2C=C(C(=O)N3CCCC3)C(OC)=CC2=C1NCC1=CC(C(N)=N)=CC=C1O ZOTPACDGKSMJRN-UHFFFAOYSA-N 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
- GPUHJPCLUJUQCD-UHFFFAOYSA-N 8-[4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)N(CC1)CCC21CNC(=O)O2 GPUHJPCLUJUQCD-UHFFFAOYSA-N 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- DMOFVXGTPDDTCI-SMSORMJASA-N ClC=1C=C2C(=NC=NC2=CC1C(=O)N1[C@@](CCC1)(C(=O)OC(C)(C)C)CN)N[C@@H](CCSC)C1=NC2=C(N1)C=CC(=C2)Cl Chemical compound ClC=1C=C2C(=NC=NC2=CC1C(=O)N1[C@@](CCC1)(C(=O)OC(C)(C)C)CN)N[C@@H](CCSC)C1=NC2=C(N1)C=CC(=C2)Cl DMOFVXGTPDDTCI-SMSORMJASA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- KDRBRQMQRZFBKA-UHFFFAOYSA-N N',4-dihydroxy-3-[[[6-methyl-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]methyl]benzenecarboximidamide Chemical compound N1=CN=C2C=C(C(=O)N3CCCC3)C(C)=CC2=C1NCC1=CC(C(=N)NO)=CC=C1O KDRBRQMQRZFBKA-UHFFFAOYSA-N 0.000 description 1
- ONXPDKGXOOORHB-BYPYZUCNSA-N N(5)-methyl-L-glutamine Chemical compound CNC(=O)CC[C@H](N)C(O)=O ONXPDKGXOOORHB-BYPYZUCNSA-N 0.000 description 1
- QQNVASVDTBYOPI-UHFFFAOYSA-N N-[(5-carbamimidoyl-2-hydroxyphenyl)methyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)NCC=2C(=CC=C(C=2)C(N)=N)O)=CC=C1C(=O)N1CCCC1 QQNVASVDTBYOPI-UHFFFAOYSA-N 0.000 description 1
- JZMTYDXWWYFOIV-UHFFFAOYSA-N N-[(5-carbamimidoyl-2-hydroxyphenyl)methyl]-4-(3-methyl-5,6-dihydro-4H-cyclopenta[c]pyrazol-1-yl)-3-(trifluoromethyl)benzamide Chemical compound C1=2CCCC=2C(C)=NN1C(C(=C1)C(F)(F)F)=CC=C1C(=O)NCC1=CC(C(N)=N)=CC=C1O JZMTYDXWWYFOIV-UHFFFAOYSA-N 0.000 description 1
- QFFOOGRFLKTZFW-UHFFFAOYSA-N N-[1-(5-carbamimidoyl-2-hydroxyphenyl)ethyl]-4-(4,5,6,7-tetrahydrobenzimidazol-1-yl)-3-(trifluoromethyl)benzamide Chemical compound C=1C=C(N2C=3CCCCC=3N=C2)C(C(F)(F)F)=CC=1C(=O)NC(C)C1=CC(C(N)=N)=CC=C1O QFFOOGRFLKTZFW-UHFFFAOYSA-N 0.000 description 1
- KOBZYVWAIIENIO-UHFFFAOYSA-N N-[1-[(5-carbamimidoyl-2-hydroxyphenyl)methylamino]-7-methylisoquinolin-6-yl]-N-cyclopentylacetamide Chemical compound C=1C2=CC=NC(NCC=3C(=CC=C(C=3)C(N)=N)O)=C2C=C(C)C=1N(C(=O)C)C1CCCC1 KOBZYVWAIIENIO-UHFFFAOYSA-N 0.000 description 1
- IMTCKVSOUDKQSW-UHFFFAOYSA-N N-[amino-[4-hydroxy-3-[[[7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]methyl]phenyl]methylidene]benzamide Chemical compound OC1=CC=C(C(=N)NC(=O)C=2C=CC=CC=2)C=C1CNC(C1=CC=2)=NC=NC1=CC=2C(=O)N1CCCC1 IMTCKVSOUDKQSW-UHFFFAOYSA-N 0.000 description 1
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- ZZBSAXFWOZVWOG-OMOCHNIRSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]-6-methylquinolin-7-yl]methanone Chemical compound N=1C2=CC=C(Cl)C=C2NC=1C(C)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCC[C@@H]1CN ZZBSAXFWOZVWOG-OMOCHNIRSA-N 0.000 description 1
- CBRMMAPWXKYFOY-UHFFFAOYSA-N [(Z)-[amino-[4-hydroxy-3-[[[6-methyl-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]methyl]phenyl]methylidene]carbamoyl]oxymethyl acetate Chemical compound CC(=O)OCOC(=O)NC(=N)C1=CC=C(O)C(CNC=2C3=CC(C)=C(C(=O)N4CCCC4)C=C3N=CN=2)=C1 CBRMMAPWXKYFOY-UHFFFAOYSA-N 0.000 description 1
- YLMSXNRSXYNMJV-UHFFFAOYSA-N [2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]quinazolin-7-yl]methanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1CN YLMSXNRSXYNMJV-UHFFFAOYSA-N 0.000 description 1
- ZZHRRQMWVFZPLU-UUSAFJCLSA-N [4-[[(1s)-1-(6-bromo-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]-6-chloroquinazolin-7-yl]-(2,5-dihydro-1h-pyrrol-2-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC(Br)=CC=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)C1NCC=C1 ZZHRRQMWVFZPLU-UUSAFJCLSA-N 0.000 description 1
- IQKAOIBKAHJEBY-PIJUOJQZSA-N [4-[[(1s)-1-(6-bromo-1h-benzimidazol-2-yl)ethyl]amino]-6-chloroquinazolin-7-yl]-(2,5-dihydro-1h-pyrrol-2-yl)methanone Chemical compound N([C@@H](C)C=1NC2=CC(Br)=CC=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)C1NCC=C1 IQKAOIBKAHJEBY-PIJUOJQZSA-N 0.000 description 1
- WVUUBWGNSHRFJO-HWYAHNCWSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]-6-methylquinazolin-7-yl]-(1,3-thiazolidin-2-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2C)=NC=NC1=CC=2C(=O)C1NCCS1 WVUUBWGNSHRFJO-HWYAHNCWSA-N 0.000 description 1
- BYOCAOZUUVQFAV-OAQYLSRUSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]-6-methylquinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2C)=NC=NC1=CC=2C(=O)N1CC=CC1 BYOCAOZUUVQFAV-OAQYLSRUSA-N 0.000 description 1
- NXKZJYBXDNTGTI-FQEVSTJZSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]-6-methylquinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2C)=NC=NC1=CC=2C(=O)N1CC=CC1 NXKZJYBXDNTGTI-FQEVSTJZSA-N 0.000 description 1
- WVBUFIWRIFMHHI-UHFFFAOYSA-N [4-[[1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]-6-methylquinolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCSC)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCCC1 WVBUFIWRIFMHHI-UHFFFAOYSA-N 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- TVRYMMKZRZBXBH-UHFFFAOYSA-N benzyl 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoate Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)OCC1=CC=CC=C1 TVRYMMKZRZBXBH-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- VOSKZNBRDMQPDA-UHFFFAOYSA-N ethyl 3-(3-carbamimidoylphenyl)-3-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]propanoate Chemical compound C=1C=CC(C(N)=N)=CC=1C(CC(=O)OCC)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 VOSKZNBRDMQPDA-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- 229940056984 integrilin Drugs 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical class OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- FMSAVQSHZTZMTE-UHFFFAOYSA-N n-(2-aminoethyl)-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCCN)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 FMSAVQSHZTZMTE-UHFFFAOYSA-N 0.000 description 1
- DLEQLZVAWNSMGJ-IBGZPJMESA-N n-[(1r)-1-(6-bromo-1h-benzimidazol-2-yl)-2-hydroxyethyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CO)C=2NC3=CC=C(Br)C=C3N=2)=CC=C1C(=O)N1CCCC1 DLEQLZVAWNSMGJ-IBGZPJMESA-N 0.000 description 1
- PKQZXEJOUIKZGR-IBGZPJMESA-N n-[(1r)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]-4-(pyrrolidine-1-carbonyl)-3-(trifluoromethyl)benzamide Chemical compound N([C@@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(=O)C(C=C1C(F)(F)F)=CC=C1C(=O)N1CCCC1 PKQZXEJOUIKZGR-IBGZPJMESA-N 0.000 description 1
- IELNPIPUEPYPPR-SQLGYAFXSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfinylpropyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCS(C)=O)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 IELNPIPUEPYPPR-SQLGYAFXSA-N 0.000 description 1
- CREMJYSQFJTZSD-VWLOTQADSA-N n-[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-phenylpropyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide Chemical compound CC1=CC(C(=O)N[C@@H](CCC=2C=CC=CC=2)C=2NC3=CC=C(Cl)C=C3N=2)=CC=C1C(=O)N1CCCC1 CREMJYSQFJTZSD-VWLOTQADSA-N 0.000 description 1
- SXZNYIIOWDSYJU-UHFFFAOYSA-N n-[1-(6-chloro-1h-benzimidazol-2-yl)ethyl]-4-(2,5-dihydropyrrole-1-carbonyl)-3-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(=O)C(C=C1C)=CC=C1C(=O)N1CC=CC1 SXZNYIIOWDSYJU-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- MXSUKUHNZNKHBL-UHFFFAOYSA-N n-[4-bromo-2-[(5-chloropyridin-2-yl)carbamoyl]-6-hydroxyphenyl]-1-propan-2-ylpiperidine-4-carboxamide Chemical compound C1CN(C(C)C)CCC1C(=O)NC1=C(O)C=C(Br)C=C1C(=O)NC1=CC=C(Cl)C=N1 MXSUKUHNZNKHBL-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 125000005547 pivalate group Chemical group 0.000 description 1
- 229940020573 plavix Drugs 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229950010535 razaxaban Drugs 0.000 description 1
- 229960001148 rivaroxaban Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- RCOSUMRTSQULBK-UHFFFAOYSA-N sodium;propan-1-olate Chemical compound [Na+].CCC[O-] RCOSUMRTSQULBK-UHFFFAOYSA-N 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229950000339 xinafoate Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
- A61K38/58—Protease inhibitors from animals; from humans from leeches, e.g. hirudin, eglin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05006711 | 2005-03-29 | ||
| PCT/EP2006/061046 WO2006103206A2 (en) | 2005-03-29 | 2006-03-27 | Combinations comprising at least one direct thrombin inhibitor for the treatment of thrombosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008534552A true JP2008534552A (ja) | 2008-08-28 |
| JP2008534552A5 JP2008534552A5 (OSRAM) | 2009-05-21 |
Family
ID=36423564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008503489A Pending JP2008534552A (ja) | 2005-03-29 | 2006-03-27 | 血栓症治療用の新規な医薬組成物 |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US20060222640A1 (OSRAM) |
| EP (1) | EP1885354A2 (OSRAM) |
| JP (1) | JP2008534552A (OSRAM) |
| KR (1) | KR20070116936A (OSRAM) |
| CN (1) | CN101151030A (OSRAM) |
| AR (1) | AR056291A1 (OSRAM) |
| AU (1) | AU2006228600A1 (OSRAM) |
| BR (1) | BRPI0608656A2 (OSRAM) |
| CA (1) | CA2602563A1 (OSRAM) |
| CL (1) | CL2010000395A1 (OSRAM) |
| EA (1) | EA015122B1 (OSRAM) |
| IL (1) | IL186267A0 (OSRAM) |
| MX (1) | MX2007010664A (OSRAM) |
| NO (1) | NO20074149L (OSRAM) |
| NZ (1) | NZ562775A (OSRAM) |
| TW (1) | TW200722089A (OSRAM) |
| UA (1) | UA92603C2 (OSRAM) |
| WO (1) | WO2006103206A2 (OSRAM) |
| ZA (1) | ZA200706698B (OSRAM) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014508138A (ja) * | 2011-01-25 | 2014-04-03 | ユニヴェルシテ カソリック ド ルーヴァン | 細胞移植のための組成物および方法 |
| JP2015508054A (ja) * | 2012-01-25 | 2015-03-16 | ユニヴェルシテ カソリック ド ルーヴァンＵｎｉｖｅｒｓｉｔｅ Ｃａｔｈｏｌｉｑｕｅ Ｄｅ Ｌｏｕｖａｉｎ | 細胞移植のための組成物および方法 |
| JP2019206543A (ja) * | 2014-06-11 | 2019-12-05 | グルバ, ディートリッヒGulba, Dietrich | 殺鼠剤としての抗凝血性化合物の使用 |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8906894B1 (en) | 2000-07-27 | 2014-12-09 | Thomas N. Thomas | Methods for preventing and treating thrombotic disorders |
| US20030181488A1 (en) | 2002-03-07 | 2003-09-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester and the salts thereof |
| DE10339862A1 (de) * | 2003-08-29 | 2005-03-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 3-[(2-{[4-(Hexyloxycarbonylamino-imino-methyl)- phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionsäure-ethylester-Methansulfonat und dessen Verwendung als Arzneimittel |
| IL159273A0 (en) * | 2003-12-09 | 2004-06-01 | Transpharma Medical Ltd | Transdermal delivery system for sustained release of polypeptides |
| CA2610757A1 (en) * | 2005-06-10 | 2006-12-14 | Transpharma Medical, Ltd. | Patch for transdermal drug delivery |
| EP2043632A2 (en) * | 2006-07-17 | 2009-04-08 | Boehringer Ingelheim International GmbH | New indications for direct thrombin inhibitors |
| US20100087488A1 (en) * | 2006-10-10 | 2010-04-08 | Boehringer Ingelheim International Gmgh | Physiologically Acceptable Salts of 3-[(2--1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester |
| DE102006051625A1 (de) | 2006-11-02 | 2008-05-08 | Bayer Materialscience Ag | Kombinationstherapie substituierter Oxazolidinone |
| WO2009057112A2 (en) * | 2007-10-29 | 2009-05-07 | Transpharma Medical, Ltd. | Vertical patch drying |
| WO2010013231A2 (en) * | 2008-07-29 | 2010-02-04 | Yeda Research And Development Co. Ltd. | Modulation of coagulation factors and effectors of same for control of transplant organ size |
| EP2323605A4 (en) * | 2008-09-10 | 2014-02-05 | Syneron Medical Ltd | TRANSDERMAL RELEASE OF OLIGOSACCHARIDES |
| TW201031651A (en) * | 2008-11-11 | 2010-09-01 | Boehringer Ingelheim Int | Method for treating or preventing thrombosis using dabigatran etexilate or a salt thereof with improved efficacy over conventional warfarin therapy |
| AR074313A1 (es) | 2008-11-11 | 2011-01-05 | Boehringer Ingelheim Int | Metodo para tratar o prevenir la trombosis utilizando etexilato de dabigatran o una sal del mismo. uso. kit |
| CA2738885A1 (en) * | 2008-11-11 | 2010-05-20 | Boehringer Ingelheim International Gmbh | Method for treating or preventing thrombosis using dabigatran etexilate or a salt thereof with improved efficacy over conventional warfarin therapy |
| EP2384196B1 (en) * | 2008-12-30 | 2017-09-13 | Johansson, Pär | Methods of identifying critically ill patients at increased risk of development of organ failure and compounds for the treatment hereof |
| CN102250099B (zh) * | 2011-05-16 | 2013-10-16 | 中国药科大学 | 一类非肽类抗凝血酶抑制剂、其制法以及医药用途 |
| WO2014001220A1 (en) | 2012-06-25 | 2014-01-03 | Boehringer Ingelheim International Gmbh | Method for prevention of stroke |
| EP2722034B1 (en) * | 2012-10-19 | 2020-09-16 | Sanovel Ilac Sanayi ve Ticaret A.S. | Oral pharmaceutical formulations comprising dabigatran |
| EP2722033A1 (en) * | 2012-10-19 | 2014-04-23 | Sanovel Ilac Sanayi ve Ticaret A.S. | Pharmaceutical Compositions of Dabigatran Free Base |
| JP6474394B2 (ja) | 2013-07-05 | 2019-02-27 | ユニベルシテ カトリック ドゥ ルーベン | ヒト成体肝臓幹細胞由来の馴化培地および肝臓障害の治療におけるその使用 |
| CN105250286A (zh) * | 2015-11-13 | 2016-01-20 | 谭惠娟 | 一种抗血栓组合物 |
| CN108236612A (zh) * | 2016-12-27 | 2018-07-03 | 李志忠 | 用于冠脉介入手术中抗凝的组合产品及其用途 |
| WO2020180489A1 (en) * | 2019-03-06 | 2020-09-10 | University Of Rochester | Anticoagulant compositions and uses thereof |
| US11654036B2 (en) | 2020-05-26 | 2023-05-23 | Elixir Medical Corporation | Anticoagulant compounds and methods and devices for their use |
| CN115192691B (zh) * | 2022-08-31 | 2025-03-04 | 晓恩医药包装材料(安庆)有限公司 | 一种阿加曲班注射液及预灌封注射器 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0920681A (ja) * | 1995-03-15 | 1997-01-21 | Behringwerke Ag | 血栓溶解処置を受けていない患者におけるヒルジンおよびアセチルサリチル酸による急性心筋梗塞の処置方法 |
| JP2001509815A (ja) * | 1997-02-18 | 2001-07-24 | ベーリンガー インゲルハイム ファルマ コマンディトゲゼルシャフト | 二置換二環式複素環化合物、これらの調製及び医薬組成物としてのこれらの使用 |
| JP2003513957A (ja) * | 1999-11-10 | 2003-04-15 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 第Ｘａ因子の阻害剤としてのＮ−アシルピロリジン−２−イルアルキルベンズアミジン誘導体 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6087380A (en) * | 1949-11-24 | 2000-07-11 | Boehringer Ingelheim Pharma Kg | Disubstituted bicyclic heterocycles, the preparations and the use thereof as pharmaceutical compositions |
| US5510330A (en) * | 1994-03-25 | 1996-04-23 | Boehringer Mannheim Gmbh | Combinations of thrombolytically active proteins and non-heparin anticoagulants, and uses thereof. |
| FR2744918B1 (fr) * | 1996-02-19 | 1998-05-07 | Sanofi Sa | Nouvelles associations de principes actifs contenant un derive de thieno(3,2-c)pyridine et un antithrombotique |
| US6414008B1 (en) * | 1997-04-29 | 2002-07-02 | Boehringer Ingelheim Pharma Kg | Disubstituted bicyclic heterocycles, the preparation thereof, and their use as pharmaceutical compositions |
| DE19834751A1 (de) * | 1998-08-01 | 2000-02-03 | Boehringer Ingelheim Pharma | Disubstituierte bicyclische Heterocyclen, ihre Herstellung und ihre Verwendung als Arzneimittel |
| GB0014134D0 (en) * | 2000-06-10 | 2000-08-02 | Astrazeneca Ab | Combination therapy |
| US8183206B2 (en) * | 2001-09-14 | 2012-05-22 | Mitsubishi Tanabe Pharma Corporation | Drugs comprising combination of antithrombotic agent with pyrazolone derivative |
| DK1485094T4 (da) * | 2002-03-07 | 2020-06-22 | Boehringer Ingelheim Int | Doseringsform til oral indgivelse af 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1h-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionsyre-ethylester eller dets salte |
| DE10235639A1 (de) * | 2002-08-02 | 2004-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Prodrugs von 1-Methyl-2-(4-amidinophenylaminomethyl)-benzimidazol-5-yl-carbonsäure-(N-2-pyridyl-N-2-hydroxycarbonylethyl)-amid, ihre Herstellung und ihre Verwendung als Arzneimittel |
| BRPI0409796A (pt) * | 2003-04-24 | 2006-05-30 | Boehringer Ingelheim Int | uso de dipiridamol ou mopidamol para tratamento e prevenção de doenças tromboembolìticas e distúrbios provocados pela formação excessiva de trombina e/ou pela expressão elevada de receptores de trombina |
-
2006
- 2006-03-26 US US11/277,503 patent/US20060222640A1/en not_active Abandoned
- 2006-03-27 MX MX2007010664A patent/MX2007010664A/es not_active Application Discontinuation
- 2006-03-27 CA CA002602563A patent/CA2602563A1/en not_active Abandoned
- 2006-03-27 UA UAA200711762A patent/UA92603C2/ru unknown
- 2006-03-27 KR KR1020077024953A patent/KR20070116936A/ko not_active Ceased
- 2006-03-27 CN CNA2006800108359A patent/CN101151030A/zh active Pending
- 2006-03-27 JP JP2008503489A patent/JP2008534552A/ja active Pending
- 2006-03-27 EP EP06725316A patent/EP1885354A2/en not_active Withdrawn
- 2006-03-27 BR BRPI0608656-0A patent/BRPI0608656A2/pt not_active IP Right Cessation
- 2006-03-27 NZ NZ562775A patent/NZ562775A/en unknown
- 2006-03-27 WO PCT/EP2006/061046 patent/WO2006103206A2/en not_active Ceased
- 2006-03-27 EA EA200701841A patent/EA015122B1/ru not_active IP Right Cessation
- 2006-03-27 AU AU2006228600A patent/AU2006228600A1/en not_active Abandoned
- 2006-03-28 TW TW095110732A patent/TW200722089A/zh unknown
- 2006-03-29 AR ARP060101205A patent/AR056291A1/es unknown
-
2007
- 2007-08-10 NO NO20074149A patent/NO20074149L/no not_active Application Discontinuation
- 2007-08-13 ZA ZA200706698A patent/ZA200706698B/xx unknown
- 2007-09-25 IL IL186267A patent/IL186267A0/en unknown
-
2010
- 2010-03-19 US US12/727,933 patent/US20100184729A1/en not_active Abandoned
- 2010-04-21 CL CL2010000395A patent/CL2010000395A1/es unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0920681A (ja) * | 1995-03-15 | 1997-01-21 | Behringwerke Ag | 血栓溶解処置を受けていない患者におけるヒルジンおよびアセチルサリチル酸による急性心筋梗塞の処置方法 |
| JP2001509815A (ja) * | 1997-02-18 | 2001-07-24 | ベーリンガー インゲルハイム ファルマ コマンディトゲゼルシャフト | 二置換二環式複素環化合物、これらの調製及び医薬組成物としてのこれらの使用 |
| JP2003513957A (ja) * | 1999-11-10 | 2003-04-15 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 第Ｘａ因子の阻害剤としてのＮ−アシルピロリジン−２−イルアルキルベンズアミジン誘導体 |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014508138A (ja) * | 2011-01-25 | 2014-04-03 | ユニヴェルシテ カソリック ド ルーヴァン | 細胞移植のための組成物および方法 |
| JP2015508054A (ja) * | 2012-01-25 | 2015-03-16 | ユニヴェルシテ カソリック ド ルーヴァンＵｎｉｖｅｒｓｉｔｅ Ｃａｔｈｏｌｉｑｕｅ Ｄｅ Ｌｏｕｖａｉｎ | 細胞移植のための組成物および方法 |
| JP2019206543A (ja) * | 2014-06-11 | 2019-12-05 | グルバ, ディートリッヒGulba, Dietrich | 殺鼠剤としての抗凝血性化合物の使用 |
| US11678659B2 (en) | 2014-06-11 | 2023-06-20 | Dietrich Gulba | Use as rodenticides of compounds that inhibit blood coagulation |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006103206A3 (en) | 2007-01-11 |
| CN101151030A (zh) | 2008-03-26 |
| US20100184729A1 (en) | 2010-07-22 |
| NO20074149L (no) | 2007-12-11 |
| AR056291A1 (es) | 2007-10-03 |
| US20060222640A1 (en) | 2006-10-05 |
| BRPI0608656A2 (pt) | 2010-01-19 |
| CA2602563A1 (en) | 2006-10-05 |
| IL186267A0 (en) | 2008-01-20 |
| TW200722089A (en) | 2007-06-16 |
| NZ562775A (en) | 2011-03-31 |
| MX2007010664A (es) | 2007-12-12 |
| AU2006228600A1 (en) | 2006-10-05 |
| WO2006103206A2 (en) | 2006-10-05 |
| EA200701841A1 (ru) | 2008-02-28 |
| EA015122B1 (ru) | 2011-06-30 |
| EP1885354A2 (en) | 2008-02-13 |
| KR20070116936A (ko) | 2007-12-11 |
| UA92603C2 (ru) | 2010-11-25 |
| CL2010000395A1 (es) | 2010-08-20 |
| ZA200706698B (en) | 2008-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008534552A (ja) | 血栓症治療用の新規な医薬組成物 | |
| CN103458690B (zh) | 治疗肺动脉高压的组合物和方法 | |
| EP3288558B1 (en) | Combinations of inhibitors of irak4 with inhibitors of btk | |
| CA3172586C (en) | IMATINIB AEROSOL COMPOUNDS AND RELATED USES | |
| TWI549954B (zh) | 經取代之２，３－二氫咪唑并［１，２－ｃ］喹唑啉鹽 | |
| MX2010012290A (es) | Combinaciones de inhibidores del receptor del factor de crecimiento endotelial vascular e inhibidores del factor de crecimiento de hepatocito para el tratamiento de cancer. | |
| CN102958540B (zh) | 含取代的2,3-二氢咪唑并[1,2-c]喹唑啉的组合 | |
| JP7150976B2 (ja) | 抗血小板剤と胃酸分泌阻害剤を含む医薬組成物 | |
| US12263157B2 (en) | Aldosterone synthase inhibitors for treating chronic kidney disease | |
| CN1511036B (zh) | 包含信号转导抑制剂和埃坡霉素衍生物的联合形式 | |
| CN118647379A (zh) | 用于治疗癌症的包含cdk2抑制剂和cdk4抑制剂的方法和给药方案 | |
| US20240016814A1 (en) | Method of treating hypertension | |
| WO2024102187A1 (en) | Combination therapy comprising bispecific antibodies comprising an nrp1 binding domain | |
| CN103582481A (zh) | A2b腺苷受体拮抗剂用于治疗心肌梗塞后患者的心力衰竭及心律不齐的用途 | |
| US20090075949A1 (en) | Use of dipyridamole in combination with antithrombotics for treatment and prevention of thromboembolic diseases | |
| CA2566081A1 (en) | Use of dipyridamole for treatment of resistance to platelet inhibitors | |
| CN104780921A (zh) | Hcv的大环蛋白酶抑制剂、非核苷hcv抑制剂和利托那韦的组合 | |
| HK1119932A (en) | Combinations comprising at least one direct thrombin inhibitor for the treatment of thrombosis | |
| US11185549B2 (en) | Combination of a PI3K-inhibitor with an androgen receptor antagonist | |
| US20190076441A1 (en) | Method of treating hypertension | |
| JP6851826B2 (ja) | がんの治療のためのｐｉｍキナーゼ阻害剤と組み合わせたペプチドエポキシケトンプロテアソーム阻害剤 | |
| JP2009500440A (ja) | 性欲障害治療用医薬組成物 | |
| JP2023075371A (ja) | 新型コロナウイルス感染症（ｃｏｖｉｄ－１９）の予防または治療剤および医薬組成物 | |
| CN101711155A (zh) | 用于治疗和预防肺动脉高压的噁唑烷酮 | |
| HK1182937B (en) | Substituted 2,3-dihydroimidazo[1,2-c]quinazoline-containing combinations |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090327 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090327 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120130 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120625 |