CA2044636A1 - Guanidines - Google Patents
GuanidinesInfo
- Publication number
- CA2044636A1 CA2044636A1 CA002044636A CA2044636A CA2044636A1 CA 2044636 A1 CA2044636 A1 CA 2044636A1 CA 002044636 A CA002044636 A CA 002044636A CA 2044636 A CA2044636 A CA 2044636A CA 2044636 A1 CA2044636 A1 CA 2044636A1
- Authority
- CA
- Canada
- Prior art keywords
- amidino
- methyl
- group
- fab
- piperidinylmethyl
- 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.)
- Abandoned
Links
- 150000002357 guanidines Chemical class 0.000 title claims abstract description 28
- 108090000190 Thrombin Proteins 0.000 claims abstract description 9
- 229960004072 thrombin Drugs 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 239000012453 solvate Substances 0.000 claims abstract description 8
- 150000004677 hydrates Chemical class 0.000 claims abstract description 5
- 206010053567 Coagulopathies Diseases 0.000 claims abstract description 4
- 108010049003 Fibrinogen Proteins 0.000 claims abstract description 4
- 102000008946 Fibrinogen Human genes 0.000 claims abstract description 4
- 230000035602 clotting Effects 0.000 claims abstract description 4
- 229940012952 fibrinogen Drugs 0.000 claims abstract description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 3
- -1 heptamethyleneimino Chemical group 0.000 claims description 143
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 93
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 80
- 150000001875 compounds Chemical class 0.000 claims description 54
- 239000002253 acid Substances 0.000 claims description 34
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- OTVHXWFANORBAK-UHFFFAOYSA-N 3-(1h-indol-3-yl)propanamide Chemical compound C1=CC=C2C(CCC(=O)N)=CNC2=C1 OTVHXWFANORBAK-UHFFFAOYSA-N 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 239000005977 Ethylene Substances 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000006303 iodophenyl group Chemical group 0.000 claims description 4
- PQJZHMCWDKOPQG-UHFFFAOYSA-N 2-anilino-2-oxoacetic acid Chemical compound OC(=O)C(=O)NC1=CC=CC=C1 PQJZHMCWDKOPQG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 210000002381 plasma Anatomy 0.000 claims description 3
- VTVXFXXWNRYTJO-VCUSLETLSA-N (2r)-4-(2-aminophenyl)-n-[(1-carbamimidoylpiperidin-3-yl)methyl]-2-(naphthalen-2-ylsulfonylamino)-4-oxobutanamide Chemical compound C1N(C(=N)N)CCCC1CNC(=O)[C@H](NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)CC(=O)C1=CC=CC=C1N VTVXFXXWNRYTJO-VCUSLETLSA-N 0.000 claims description 2
- DNRSDTTWBDTSTQ-UHFFFAOYSA-N 2-prop-2-enoyl-1,4-oxazepane-3-carboxylic acid Chemical group OC(=O)C1NCCCOC1C(=O)C=C DNRSDTTWBDTSTQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000748 anthracen-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C([H])=C([*])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 2
- 125000003435 aroyl group Chemical group 0.000 claims description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- YZINREIXJRZNBY-UHFFFAOYSA-N n-ethenylpiperidine-2-carboxamide Chemical group C=CNC(=O)C1CCCCN1 YZINREIXJRZNBY-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000011282 treatment Methods 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 8
- WFNIHQZMCAGWQO-UQBPGWFLSA-N (3r)-n-[[(3s)-1-carbamimidoylpiperidin-3-yl]methyl]-2-naphthalen-2-ylsulfonyl-3,4-dihydro-1h-isoquinoline-3-carboxamide Chemical compound C1N(C(=N)N)CCC[C@H]1CNC(=O)[C@@H]1N(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CC2=CC=CC=C2C1 WFNIHQZMCAGWQO-UQBPGWFLSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 238000010640 amide synthesis reaction Methods 0.000 abstract 1
- 230000032050 esterification Effects 0.000 abstract 1
- 238000005886 esterification reaction Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 264
- 239000000243 solution Substances 0.000 description 160
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 144
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 90
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 88
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 81
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 81
- 239000000047 product Substances 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 74
- 239000011541 reaction mixture Substances 0.000 description 64
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- 229940073584 methylene chloride Drugs 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 238000001704 evaporation Methods 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 37
- 229910002027 silica gel Inorganic materials 0.000 description 37
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 36
- 230000008020 evaporation Effects 0.000 description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 31
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 26
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000007792 addition Methods 0.000 description 21
- 238000001035 drying Methods 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 229960000443 hydrochloric acid Drugs 0.000 description 20
- 235000011167 hydrochloric acid Nutrition 0.000 description 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 229940086542 triethylamine Drugs 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 230000000875 corresponding effect Effects 0.000 description 11
- 229940080818 propionamide Drugs 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 10
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- VYIBCOSBNVFEIW-UHFFFAOYSA-N 3-phenylpropanamide Chemical compound NC(=O)CCC1=CC=CC=C1 VYIBCOSBNVFEIW-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 8
- CZOWYKOQKWYITK-HXUWFJFHSA-N (2r)-3-(1h-indol-3-yl)-2-(naphthalen-2-ylsulfonylamino)propanoic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)N[C@H](CC=3C4=CC=CC=C4NC=3)C(=O)O)=CC=C21 CZOWYKOQKWYITK-HXUWFJFHSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000001828 Gelatine Substances 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 125000003386 piperidinyl group Chemical group 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 5
- OJCLHERKFHHUTB-VIFPVBQESA-N tert-butyl (3s)-3-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H](CO)C1 OJCLHERKFHHUTB-VIFPVBQESA-N 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- UWTHONUVTLWJQP-GOSISDBHSA-N (2r)-3-(4-aminophenyl)-2-(naphthalen-2-ylsulfonylamino)propanoic acid Chemical compound C1=CC(N)=CC=C1C[C@H](C(O)=O)NS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 UWTHONUVTLWJQP-GOSISDBHSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- 239000003810 Jones reagent Substances 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 239000001120 potassium sulphate Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 3
- 235000019759 Maize starch Nutrition 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 3
- 229910005948 SO2Cl Inorganic materials 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 229960003767 alanine Drugs 0.000 description 3
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 3
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical compound OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- WPWXYQIMXTUMJB-VIFPVBQESA-N tert-butyl (3s)-3-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H](CN)C1 WPWXYQIMXTUMJB-VIFPVBQESA-N 0.000 description 3
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- UIKNYKPWABRGEP-IENPIDJESA-N tert-butyl (2S)-3-azido-2-methylpiperidine-1-carboxylate Chemical compound N(=[N+]=[N-])C1[C@@H](N(CCC1)C(=O)OC(C)(C)C)C UIKNYKPWABRGEP-IENPIDJESA-N 0.000 description 1
- ACZCGPCKRWNVEX-MZOAHBAQSA-N tert-butyl (2r)-2-[[(2s)-1-[(1-carbamimidoylpiperidin-3-yl)methylamino]-3-(naphthalen-2-ylsulfonylamino)-1-oxopropan-2-yl]carbamoyl]piperidine-1-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC(C)(C)OC(=O)N1CCCC[C@@H]1C(=O)N[C@H](C(=O)NCC1CN(CCC1)C(N)=N)CNS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 ACZCGPCKRWNVEX-MZOAHBAQSA-N 0.000 description 1
- SNCLDRJCUJCDQI-ZDUSSCGKSA-N tert-butyl (3S)-3-[(4-chlorophenyl)sulfonyloxymethyl]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@@H]1COS(=O)(=O)C1=CC=C(Cl)C=C1 SNCLDRJCUJCDQI-ZDUSSCGKSA-N 0.000 description 1
- WPWXYQIMXTUMJB-SECBINFHSA-N tert-butyl (3r)-3-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H](CN)C1 WPWXYQIMXTUMJB-SECBINFHSA-N 0.000 description 1
- WZUVETOACDLIHB-GFCCVEGCSA-N tert-butyl (3r)-3-(butanoyloxymethyl)piperidine-1-carboxylate Chemical compound CCCC(=O)OC[C@@H]1CCCN(C(=O)OC(C)(C)C)C1 WZUVETOACDLIHB-GFCCVEGCSA-N 0.000 description 1
- KLUCUVWOMVXUKZ-LBPRGKRZSA-N tert-butyl (3s)-3-(2-methylpropanoyloxymethyl)piperidine-1-carboxylate Chemical compound CC(C)C(=O)OC[C@H]1CCCN(C(=O)OC(C)(C)C)C1 KLUCUVWOMVXUKZ-LBPRGKRZSA-N 0.000 description 1
- IKKHJUNAQMPJBI-INIZCTEOSA-N tert-butyl (3s)-3-(phenylmethoxycarbonylaminomethyl)piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@H]1CNC(=O)OCC1=CC=CC=C1 IKKHJUNAQMPJBI-INIZCTEOSA-N 0.000 description 1
- YKQKKWXIIRRHLJ-VIFPVBQESA-N tert-butyl (4S)-2,2-dimethyl-4-(methylsulfonyloxymethyl)-1,3-oxazolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)N1[C@H](COS(C)(=O)=O)COC1(C)C YKQKKWXIIRRHLJ-VIFPVBQESA-N 0.000 description 1
- BMOFQGPNVWTCRM-CQSZACIVSA-N tert-butyl (4r)-2,2-dimethyl-4-[(4-methyl-2,5-dioxo-3h-1,4-benzodiazepin-1-yl)methyl]-1,3-oxazolidine-3-carboxylate Chemical compound C12=CC=CC=C2C(=O)N(C)CC(=O)N1C[C@@H]1COC(C)(C)N1C(=O)OC(C)(C)C BMOFQGPNVWTCRM-CQSZACIVSA-N 0.000 description 1
- DWFOEHLGMZJBAA-MRVPVSSYSA-N tert-butyl (4r)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)N1[C@H](CO)COC1(C)C DWFOEHLGMZJBAA-MRVPVSSYSA-N 0.000 description 1
- KBDJCRUNHXFKLI-AWEZNQCLSA-N tert-butyl (4s)-2,2-dimethyl-4-[(4-methylphenyl)sulfonyloxymethyl]-1,3-oxazolidine-3-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@H]1N(C(=O)OC(C)(C)C)C(C)(C)OC1 KBDJCRUNHXFKLI-AWEZNQCLSA-N 0.000 description 1
- HRAQVANQBLAPFF-UHFFFAOYSA-N tert-butyl 1-(aminomethyl)piperidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1CCCN(CN)C1 HRAQVANQBLAPFF-UHFFFAOYSA-N 0.000 description 1
- MTMBHUYOIZWQAJ-UHFFFAOYSA-N tert-butyl 2-(aminomethyl)morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOC(CN)C1 MTMBHUYOIZWQAJ-UHFFFAOYSA-N 0.000 description 1
- XXLGVNOSUFGGID-UHFFFAOYSA-N tert-butyl 2-(azidomethyl)morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOC(CN=[N+]=[N-])C1 XXLGVNOSUFGGID-UHFFFAOYSA-N 0.000 description 1
- FJYBLMJHXRWDAQ-UHFFFAOYSA-N tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOC(CO)C1 FJYBLMJHXRWDAQ-UHFFFAOYSA-N 0.000 description 1
- KECCCNNRVKAUBS-UHFFFAOYSA-N tert-butyl 2-(phenylmethoxymethyl)morpholine-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCOC1COCC1=CC=CC=C1 KECCCNNRVKAUBS-UHFFFAOYSA-N 0.000 description 1
- PGJRRUATHAJQTQ-UHFFFAOYSA-N tert-butyl 2-[(4-chlorophenyl)sulfonyloxymethyl]morpholine-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCOC1COS(=O)(=O)C1=CC=C(Cl)C=C1 PGJRRUATHAJQTQ-UHFFFAOYSA-N 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
- WZUVETOACDLIHB-UHFFFAOYSA-N tert-butyl 3-(butanoyloxymethyl)piperidine-1-carboxylate Chemical compound CCCC(=O)OCC1CCCN(C(=O)OC(C)(C)C)C1 WZUVETOACDLIHB-UHFFFAOYSA-N 0.000 description 1
- OJCLHERKFHHUTB-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(CO)C1 OJCLHERKFHHUTB-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/12—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- C07D265/32—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH225090 | 1990-07-05 | ||
CH2250/90 | 1990-07-05 | ||
CH1315/91 | 1991-05-02 | ||
CH131591 | 1991-05-02 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2044636A1 true CA2044636A1 (en) | 1992-01-06 |
Family
ID=25687300
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002044636A Abandoned CA2044636A1 (en) | 1990-07-05 | 1991-06-14 | Guanidines |
Country Status (19)
Country | Link |
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US (6) | US5260307A (en, 2012) |
EP (1) | EP0468231B1 (en, 2012) |
JP (1) | JPH0730022B2 (en, 2012) |
KR (1) | KR100218600B1 (en, 2012) |
AT (1) | ATE111890T1 (en, 2012) |
AU (1) | AU650458B2 (en, 2012) |
CA (1) | CA2044636A1 (en, 2012) |
DE (1) | DE59103021D1 (en, 2012) |
DK (1) | DK0468231T3 (en, 2012) |
ES (1) | ES2061125T3 (en, 2012) |
FI (1) | FI102966B (en, 2012) |
HU (1) | HU217815B (en, 2012) |
IE (1) | IE66047B1 (en, 2012) |
IL (3) | IL98690A (en, 2012) |
MC (1) | MC2261A1 (en, 2012) |
NO (1) | NO177704C (en, 2012) |
NZ (1) | NZ238773A (en, 2012) |
PT (1) | PT98221B (en, 2012) |
TW (1) | TW201303B (en, 2012) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5847125A (en) * | 1992-01-09 | 1998-12-08 | James Black Foundation Limited | Amino acid derivatives with anticholecystokinin activity |
Families Citing this family (87)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW201303B (en, 2012) * | 1990-07-05 | 1993-03-01 | Hoffmann La Roche | |
SE9103612D0 (sv) * | 1991-12-04 | 1991-12-04 | Astra Ab | New peptide derivatives |
SG48063A1 (en) * | 1992-03-06 | 1998-04-17 | Hoffmann La Roche | Sulfonamidocarboxamides |
TW223629B (en, 2012) * | 1992-03-06 | 1994-05-11 | Hoffmann La Roche | |
DE4242655A1 (de) * | 1992-12-17 | 1994-06-23 | Behringwerke Ag | Verwendung von Thrombin-Inhibitoren zur Inhibition okularer Fibrinbildung |
CA2122397A1 (en) * | 1993-05-03 | 1994-11-04 | Spencer D. Kimball | Guanidinyl- or amidinyl-substituted heterocyclic thrombin inhibitors |
JPH06340619A (ja) * | 1993-05-03 | 1994-12-13 | Bristol Myers Squibb Co | グアニジニルまたはアミジニル置換メチルアミノ複素環トロンビン抑制剤 |
US5783563A (en) * | 1993-06-03 | 1998-07-21 | Astra Aktiebolag | Method for treatment or prophylaxis of venous thrombosis |
US6984627B1 (en) | 1993-06-03 | 2006-01-10 | Astrazeneca Ab | Peptide derivatives |
SE9301916D0 (sv) * | 1993-06-03 | 1993-06-03 | Ab Astra | New peptides derivatives |
TW394760B (en) * | 1993-09-07 | 2000-06-21 | Hoffmann La Roche | Novel Carboxamides, process for their preparation and pharmaceutical composition containing the same |
US5770575A (en) * | 1994-03-16 | 1998-06-23 | Ortho Pharmaceutical Corporation | Nipecotic acid derivatives as antithrombotic compounds |
EP0684238A3 (en) * | 1994-04-27 | 1997-01-15 | Hoffmann La Roche | Process for the preparation of dicarboxamides. |
US5536867A (en) * | 1994-04-27 | 1996-07-16 | Hoffmann-La Roche Inc. | Process for the manufacture of dicarboxamides |
US5637599A (en) * | 1994-06-17 | 1997-06-10 | Corvas International, Inc. | Arginine mimic derivatives as enzyme inhibitors |
SE9404196D0 (sv) * | 1994-12-02 | 1994-12-02 | Astra Ab | New antithrombotic formulation |
US5731439A (en) * | 1995-03-24 | 1998-03-24 | The Dupont Merck Pharmaceutical Company | Piperidine containing aminobornic acids |
SA96170106A (ar) | 1995-07-06 | 2005-12-03 | أسترا أكتيبولاج | مشتقات حامض أميني جديدة |
DE69625505T2 (de) * | 1995-09-29 | 2003-11-13 | 3-Dimensional Pharmaceuticals, Inc. | Guanidino proteiase inhibitoren |
US5792769A (en) * | 1995-09-29 | 1998-08-11 | 3-Dimensional Pharmaceuticals, Inc. | Guanidino protease inhibitors |
BR9611479B1 (pt) * | 1995-11-13 | 2009-01-13 | Ácidos alfa-iminoidroxÂmicos e carboxÍlicos n-substituÍdos cÍclicos e heterocÍclicos. | |
AR005245A1 (es) | 1995-12-21 | 1999-04-28 | Astrazeneca Ab | Prodrogas de inhibidores de trombina, una formulación farmaceutica que las comprende, el uso de dichas prodrogas para la manufactura de un medicamento y un procedimiento para su preparacion |
BR9612360A (pt) | 1995-12-29 | 1999-07-13 | Dimensional Pharm Inc | Inibidores de amidino protease |
ZA9756B (en) * | 1996-01-16 | 1997-07-17 | Warner Lambert Co | Process for preparing 4,6-disubstituted pyrido[3,4-d]-pyrimidines |
US6919375B1 (en) | 1996-01-23 | 2005-07-19 | Shionogi & Co., Ltd. | Sulfonated amino acid derivatives and metalloproteinase inhibitors containing the same |
AU715764B2 (en) | 1996-01-23 | 2000-02-10 | Shionogi & Co., Ltd. | Sulfonated amino acid derivatives and metalloproteinase inhibitors containing the same |
CA2242416C (en) * | 1996-01-23 | 2006-03-21 | Shionogi & Co., Ltd. | Sulfonated amino acid derivatives and metalloproteinase inhibitors containing the same |
US6025355A (en) | 1997-05-19 | 2000-02-15 | Cambridge Neuroscience, Inc. | Pharmaceutically active compounds and methods of use |
US5780480A (en) * | 1996-02-28 | 1998-07-14 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
SE9602263D0 (sv) * | 1996-06-07 | 1996-06-07 | Astra Ab | New amino acid derivatives |
US5668289A (en) * | 1996-06-24 | 1997-09-16 | Merck & Co., Inc. | Pyridinone thrombin inhibitors |
SE9602646D0 (sv) | 1996-07-04 | 1996-07-04 | Astra Ab | Pharmaceutically-useful compounds |
US6242198B1 (en) | 1996-07-25 | 2001-06-05 | Cambridge Neuroscience, Inc. | Methods of treatment of eye trauma and disorders |
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1991
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- 1991-06-14 CA CA002044636A patent/CA2044636A1/en not_active Abandoned
- 1991-06-24 US US07/719,429 patent/US5260307A/en not_active Expired - Fee Related
- 1991-06-27 MC MC912199A patent/MC2261A1/xx unknown
- 1991-06-28 NZ NZ238773A patent/NZ238773A/en unknown
- 1991-07-01 JP JP3185774A patent/JPH0730022B2/ja not_active Expired - Lifetime
- 1991-07-01 IL IL9869091A patent/IL98690A/en unknown
- 1991-07-01 IL IL11271291A patent/IL112712A/en not_active IP Right Cessation
- 1991-07-01 HU HU206/91A patent/HU217815B/hu not_active IP Right Cessation
- 1991-07-01 AU AU79490/91A patent/AU650458B2/en not_active Ceased
- 1991-07-02 EP EP91110928A patent/EP0468231B1/de not_active Expired - Lifetime
- 1991-07-02 ES ES91110928T patent/ES2061125T3/es not_active Expired - Lifetime
- 1991-07-02 AT AT91110928T patent/ATE111890T1/de active
- 1991-07-02 DE DE59103021T patent/DE59103021D1/de not_active Expired - Fee Related
- 1991-07-02 DK DK91110928.8T patent/DK0468231T3/da not_active Application Discontinuation
- 1991-07-04 IE IE234491A patent/IE66047B1/en not_active IP Right Cessation
- 1991-07-04 PT PT98221A patent/PT98221B/pt not_active IP Right Cessation
- 1991-07-04 KR KR1019910011300A patent/KR100218600B1/ko not_active Expired - Fee Related
- 1991-07-04 NO NO912626A patent/NO177704C/no not_active IP Right Cessation
- 1991-07-05 FI FI913282A patent/FI102966B/fi active
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1993
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1994
- 1994-11-22 US US08/343,168 patent/US5532232A/en not_active Expired - Fee Related
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1995
- 1995-02-21 IL IL11271295A patent/IL112712A0/xx unknown
- 1995-06-07 US US08/473,060 patent/US5595999A/en not_active Expired - Fee Related
- 1995-08-04 US US08/511,428 patent/US5583133A/en not_active Expired - Fee Related
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1996
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US5847125A (en) * | 1992-01-09 | 1998-12-08 | James Black Foundation Limited | Amino acid derivatives with anticholecystokinin activity |
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