CZ20013931A3 - Nové sloučeniny - Google Patents
Nové sloučeniny Download PDFInfo
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- CZ20013931A3 CZ20013931A3 CZ20013931A CZ20013931A CZ20013931A3 CZ 20013931 A3 CZ20013931 A3 CZ 20013931A3 CZ 20013931 A CZ20013931 A CZ 20013931A CZ 20013931 A CZ20013931 A CZ 20013931A CZ 20013931 A3 CZ20013931 A3 CZ 20013931A3
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- CZ
- Czechia
- Prior art keywords
- group
- alkyl
- compound
- amino
- tert
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 142
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 239000012453 solvate Substances 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 27
- 108090000201 Carboxypeptidase B2 Proteins 0.000 claims abstract description 22
- 102000003847 Carboxypeptidase B2 Human genes 0.000 claims abstract description 21
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 239000004480 active ingredient Substances 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 230000008569 process Effects 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 4
- -1 amino, amidino Chemical group 0.000 claims description 84
- 239000000203 mixture Substances 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 229910052760 oxygen Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 239000001301 oxygen Chemical group 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 239000003112 inhibitor Substances 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- 125000005110 aryl thio group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 239000003146 anticoagulant agent Substances 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 230000007246 mechanism Effects 0.000 claims description 6
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004442 acylamino group Chemical group 0.000 claims description 5
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000005239 aroylamino group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 239000012312 sodium hydride Substances 0.000 claims description 5
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 4
- 102000003938 Thromboxane Receptors Human genes 0.000 claims description 4
- 108090000300 Thromboxane Receptors Proteins 0.000 claims description 4
- 108010069102 Thromboxane-A synthase Proteins 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229940127218 antiplatelet drug Drugs 0.000 claims description 4
- 229960004676 antithrombotic agent Drugs 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 claims description 4
- 229960001123 epoprostenol Drugs 0.000 claims description 4
- 239000002319 fibrinogen receptor antagonist Substances 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 claims description 4
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 150000003536 tetrazoles Chemical class 0.000 claims description 2
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims 3
- 102000007466 Purinergic P2 Receptors Human genes 0.000 claims 3
- 108010085249 Purinergic P2 Receptors Proteins 0.000 claims 3
- 239000005557 antagonist Substances 0.000 claims 2
- 230000002785 anti-thrombosis Effects 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 230000010534 mechanism of action Effects 0.000 claims 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 229940044551 receptor antagonist Drugs 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
- 239000000243 solution Substances 0.000 description 95
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 17
- 239000012267 brine Substances 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- 229960001701 chloroform Drugs 0.000 description 9
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 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 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 230000020764 fibrinolysis Effects 0.000 description 8
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 229940012957 plasmin Drugs 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 235000019260 propionic acid Nutrition 0.000 description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- FINBILACHLBQQI-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-3-methylbutanedioic acid Chemical compound OC(=O)C(C)C(C(O)=O)CC1=CC=C(N)N=C1 FINBILACHLBQQI-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 102000013566 Plasminogen Human genes 0.000 description 4
- 108010051456 Plasminogen Proteins 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- SXRIHRGQDXYDBS-UHFFFAOYSA-N methyl 2-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate Chemical compound COC(=O)C(O)CCCNC(=O)OC(C)(C)C SXRIHRGQDXYDBS-UHFFFAOYSA-N 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- GPDBIGSFXXKWQR-UHFFFAOYSA-N tert-butyl n-(4-formylcyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(C=O)CC1 GPDBIGSFXXKWQR-UHFFFAOYSA-N 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 3
- XGFNIBFPQHGAQO-UHFFFAOYSA-N 2-[[hydroxy(3-phenylpropyl)phosphoryl]methyl]-3-[6-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-3-yl]propanoic acid Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC=C1CC(C(O)=O)CP(O)(=O)CCCC1=CC=CC=C1 XGFNIBFPQHGAQO-UHFFFAOYSA-N 0.000 description 3
- HUIRFPGTLVLDIV-UHFFFAOYSA-N 2-[hydroxy-[2-methyl-1-[[3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]propyl]phosphoryl]oxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound C=1C=CC=CC=1COC(=O)NC(C(=O)NC(C(C)C)P(O)(=O)OC(CCCNC(=O)OC(C)(C)C)C(O)=O)CC1=CC=CC=C1 HUIRFPGTLVLDIV-UHFFFAOYSA-N 0.000 description 3
- ORSAWGFRKAADJV-UHFFFAOYSA-N 2-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC(O)C(O)=O ORSAWGFRKAADJV-UHFFFAOYSA-N 0.000 description 3
- JBWXFZGQNXBJJO-UHFFFAOYSA-N 3-O-tert-butyl 1-O-methyl 2-hydroxy-2-propylpropanedioate Chemical compound CCCC(O)(C(=O)OC)C(=O)OC(C)(C)C JBWXFZGQNXBJJO-UHFFFAOYSA-N 0.000 description 3
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 3
- XXWKRRIGSWTRJG-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxy]-3-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-4-yl]methyl]-4-oxobutanoic acid Chemical compound CC(C)(C)OC(=O)NC1=CC(CC(CC(O)=O)C(=O)OC(C)(C)C)=CC=N1 XXWKRRIGSWTRJG-UHFFFAOYSA-N 0.000 description 3
- KXMRDHPZQHAXML-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1CCC(C(O)=O)CC1 KXMRDHPZQHAXML-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 102000005367 Carboxypeptidases Human genes 0.000 description 3
- 108010006303 Carboxypeptidases Proteins 0.000 description 3
- 206010053567 Coagulopathies Diseases 0.000 description 3
- 102000009123 Fibrin Human genes 0.000 description 3
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- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 108010087750 lysyl-plasminogen Proteins 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- OBPGMLSEPRREAR-UHFFFAOYSA-N methoxy-[2-methyl-1-(phenylmethoxycarbonylamino)propyl]phosphinic acid Chemical compound COP(O)(=O)C(C(C)C)NC(=O)OCC1=CC=CC=C1 OBPGMLSEPRREAR-UHFFFAOYSA-N 0.000 description 1
- VHHLYIMUUOVLLE-UHFFFAOYSA-N methyl 2-[methoxy-[2-methyl-1-(phenylmethoxycarbonylamino)propyl]phosphoryl]oxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate Chemical compound CC(C)(C)OC(=O)NCCCC(C(=O)OC)OP(=O)(OC)C(C(C)C)NC(=O)OCC1=CC=CC=C1 VHHLYIMUUOVLLE-UHFFFAOYSA-N 0.000 description 1
- NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- IVMHDOBGNQOUHO-UHFFFAOYSA-N oxathiane Chemical compound C1CCSOC1 IVMHDOBGNQOUHO-UHFFFAOYSA-N 0.000 description 1
- OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical compound OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 1
- 230000033885 plasminogen activation Effects 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 230000009124 positive feedback regulation Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000000719 purinergic P2Y receptor antagonist Substances 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 108010073863 saruplase Proteins 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Chemical class 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- VYSGYNGIGPQSJG-UHFFFAOYSA-N tert-butyl 3-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)methyl]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC1CC1C(=O)OC(C)(C)OC1=O VYSGYNGIGPQSJG-UHFFFAOYSA-N 0.000 description 1
- PSRHRFNKESVOEL-UHFFFAOYSA-N tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC=O)CC1 PSRHRFNKESVOEL-UHFFFAOYSA-N 0.000 description 1
- VDWPAQLWZPPAHB-UHFFFAOYSA-N tert-butyl 4-[benzyl(phenylmethoxy)amino]-2-[[6-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-3-yl]methyl]-4-oxobutanoate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC=C1CC(C(=O)OC(C)(C)C)CC(=O)N(OCC=1C=CC=CC=1)CC1=CC=CC=C1 VDWPAQLWZPPAHB-UHFFFAOYSA-N 0.000 description 1
- WZROBBWIJBBWQP-UHFFFAOYSA-N tert-butyl n-(5-formylpyridin-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C=O)C=N1 WZROBBWIJBBWQP-UHFFFAOYSA-N 0.000 description 1
- DRDOWHZVHJBWFU-UHFFFAOYSA-N tert-butyl n-[4-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)methyl]pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC(CC2C(OC(C)(C)OC2=O)=O)=C1 DRDOWHZVHJBWFU-UHFFFAOYSA-N 0.000 description 1
- VCYMEIIREZLGFN-UHFFFAOYSA-N tert-butyl n-[4-[methoxy(methyl)carbamoyl]cyclohexyl]carbamate Chemical compound CON(C)C(=O)C1CCC(NC(=O)OC(C)(C)C)CC1 VCYMEIIREZLGFN-UHFFFAOYSA-N 0.000 description 1
- BODGQAXTVKKESN-UHFFFAOYSA-N tert-butyl n-[5-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)methyl]pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC=C1CC1C(=O)OC(C)(C)OC1=O BODGQAXTVKKESN-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- QRQYWLSTYOAOQW-UHFFFAOYSA-N triethyl 1-[[6-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-3-yl]methyl]hexane-1,1,2-tricarboxylate Chemical compound CCCCC(C(=O)OCC)C(C(=O)OCC)(C(=O)OCC)CC1=CC=C(NC(=O)OC(C)(C)C)N=C1 QRQYWLSTYOAOQW-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- 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
- C07D211/34—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- 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
- A61K31/13—Amines
- A61K31/132—Amines having two or more amino groups, e.g. spermidine, putrescine
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/09—Diamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Hematology (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)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9901572A SE9901572D0 (sv) | 1999-05-03 | 1999-05-03 | New compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ20013931A3 true CZ20013931A3 (cs) | 2002-04-17 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20013931A CZ20013931A3 (cs) | 1999-05-03 | 2000-05-03 | Nové sloučeniny |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US7354895B1 (enExample) |
| EP (1) | EP1180099A1 (enExample) |
| JP (1) | JP4270759B2 (enExample) |
| KR (1) | KR20020010631A (enExample) |
| CN (1) | CN1358187A (enExample) |
| AR (1) | AR028826A1 (enExample) |
| AU (1) | AU4447100A (enExample) |
| BR (1) | BR0010256A (enExample) |
| CA (1) | CA2371215A1 (enExample) |
| CZ (1) | CZ20013931A3 (enExample) |
| EE (1) | EE200100573A (enExample) |
| HK (1) | HK1042493A1 (enExample) |
| HU (1) | HUP0202379A3 (enExample) |
| IL (1) | IL145953A0 (enExample) |
| IS (1) | IS6141A (enExample) |
| MX (1) | MXPA01011043A (enExample) |
| NO (1) | NO20015374L (enExample) |
| PL (1) | PL356140A1 (enExample) |
| SE (1) | SE9901572D0 (enExample) |
| SK (1) | SK15662001A3 (enExample) |
| TR (1) | TR200103144T2 (enExample) |
| WO (1) | WO2000066550A1 (enExample) |
| ZA (2) | ZA200108967B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1187360C (zh) * | 1999-09-14 | 2005-02-02 | 明治制果株式会社 | 有羧基肽酶b抑制活性的膦酸衍生物 |
| PL361054A1 (en) * | 2000-08-17 | 2004-09-20 | Pfizer Inc. | Substituted imidazoles as tafia inhibitors |
| SE0103272D0 (sv) * | 2001-09-28 | 2001-09-28 | Astrazeneca Ab | Chemical compounds |
| US6713496B2 (en) | 2002-01-22 | 2004-03-30 | Pfizer Inc | 3-(imidazolyl)-2-alkoxypropanoic acids |
| JP2005520811A (ja) * | 2002-01-22 | 2005-07-14 | ファイザー・インク | ＴＡＦＩａインヒビターとしての３−（イミダゾリル）−２−アルコキシプロパン酸 |
| MXPA04005940A (es) | 2002-01-22 | 2004-09-13 | Pfizer | Acidos 3-(imidazolil)-2-aminopropanoicos. |
| RU2323223C2 (ru) | 2002-03-21 | 2008-04-27 | Шеринг Акциенгезельшафт | Ингибиторы карбоксипептидазы b плазмы (крови) |
| AU2009310841A1 (en) | 2008-10-29 | 2010-05-06 | Taisho Pharmaceutical Co., Ltd. | Compounds having TAFIa inhibitory activity |
| IL285108B2 (en) | 2019-02-08 | 2024-10-01 | Astrazeneca Ab | Arginase inhibitors and methods of use thereof |
| CN111110837B (zh) * | 2020-01-06 | 2022-11-25 | 中国人民解放军陆军军医大学 | 一种羧肽酶抑制剂在制备预防重症致死性轮状病毒感染药物中的应用 |
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| US2516307A (en) * | 1949-01-06 | 1950-07-25 | Gen Mills Inc | Vinyl resins plasticized with cyano esters |
| US4560680A (en) * | 1982-03-15 | 1985-12-24 | E. R. Squibb & Sons, Inc. | Aminoalkyl and related substituted phosphinic acid angiotensin converting enzyme inhibitors |
| US4849414A (en) * | 1986-06-11 | 1989-07-18 | E. R. Squibb & Sons, Inc. | Substituted aminoalkanoylaminoalkyl phosphonate angiotensin converting enzyme inhibitors |
| FR2610951B1 (fr) * | 1987-02-17 | 1989-05-05 | Aerospatiale | Armature tissee pour materiau composite |
| IL86951A (en) * | 1987-07-06 | 1996-07-23 | Procter & Gamble Pharma | Methylene phosphonoalkylphosphinates and pharmaceutical preparations containing them |
| HUT68010A (en) * | 1991-12-17 | 1995-05-29 | Procter & Gamble Pharma | The use of bisphonates and parathyroid hormone for the treatment of osteoporosis |
| US5550119A (en) * | 1995-03-02 | 1996-08-27 | Ciba-Geigy Corporation | Phosphono substituted tetrazole derivatives as ECE inhibitors |
| US5672592A (en) * | 1996-06-17 | 1997-09-30 | Guilford Pharmaceuticals Inc. | Certain phosphonomethyl-pentanedioic acid derivatives thereof |
| JP3440305B2 (ja) * | 1997-04-02 | 2003-08-25 | 高砂香料工業株式会社 | ７−（ｎ−置換アミノ）−２−フェニルヘプタン酸 エステル誘導体及び該誘導体の製造方法 |
| EE04295B1 (et) | 1997-02-27 | 2004-06-15 | American Cyanamid Company | N-hüdroksü-2-(alküül-, arüül- või heteroarüülsulfanüül-, -sulfinüül- või-sulfonüül-)-3-asendatud-alküülamiidid, -arüülamiidid või -heteroarüülamiididkui maatriksmetalloproteinaasi inhibiitorid |
| SE9901573D0 (sv) * | 1999-05-03 | 1999-05-03 | Astra Ab | New compounds |
| AR023819A1 (es) * | 1999-05-03 | 2002-09-04 | Astrazeneca Ab | FORMULACIoN FARMACEUTICA, KIT DE PARTES Y UTILIZACION DE DICHA FORMULACION |
| CN1187360C (zh) * | 1999-09-14 | 2005-02-02 | 明治制果株式会社 | 有羧基肽酶b抑制活性的膦酸衍生物 |
-
1999
- 1999-05-03 SE SE9901572A patent/SE9901572D0/xx unknown
-
2000
- 2000-04-28 AR ARP000102082A patent/AR028826A1/es not_active Application Discontinuation
- 2000-05-03 AU AU44471/00A patent/AU4447100A/en not_active Abandoned
- 2000-05-03 MX MXPA01011043A patent/MXPA01011043A/es unknown
- 2000-05-03 CN CN00809484A patent/CN1358187A/zh active Pending
- 2000-05-03 HK HK02104304.1A patent/HK1042493A1/zh unknown
- 2000-05-03 EP EP00925844A patent/EP1180099A1/en not_active Ceased
- 2000-05-03 KR KR1020017014014A patent/KR20020010631A/ko not_active Withdrawn
- 2000-05-03 SK SK1566-2001A patent/SK15662001A3/sk unknown
- 2000-05-03 TR TR2001/03144T patent/TR200103144T2/xx unknown
- 2000-05-03 IL IL14595300A patent/IL145953A0/xx unknown
- 2000-05-03 CZ CZ20013931A patent/CZ20013931A3/cs unknown
- 2000-05-03 PL PL00356140A patent/PL356140A1/xx not_active Application Discontinuation
- 2000-05-03 EE EEP200100573A patent/EE200100573A/xx unknown
- 2000-05-03 WO PCT/SE2000/000846 patent/WO2000066550A1/en not_active Ceased
- 2000-05-03 US US09/600,660 patent/US7354895B1/en not_active Expired - Fee Related
- 2000-05-03 JP JP2000615381A patent/JP4270759B2/ja not_active Expired - Fee Related
- 2000-05-03 BR BR0010256-3A patent/BR0010256A/pt not_active Application Discontinuation
- 2000-05-03 CA CA002371215A patent/CA2371215A1/en not_active Abandoned
- 2000-05-03 HU HU0202379A patent/HUP0202379A3/hu unknown
-
2001
- 2001-10-30 ZA ZA200108967A patent/ZA200108967B/en unknown
- 2001-10-30 ZA ZA200108966A patent/ZA200108966B/en unknown
- 2001-11-01 IS IS6141A patent/IS6141A/is unknown
- 2001-11-02 NO NO20015374A patent/NO20015374L/no not_active Application Discontinuation
-
2005
- 2005-12-02 US US11/293,060 patent/US7423012B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| PL356140A1 (en) | 2004-06-14 |
| NO20015374D0 (no) | 2001-11-02 |
| US7354895B1 (en) | 2008-04-08 |
| KR20020010631A (ko) | 2002-02-04 |
| WO2000066550A8 (en) | 2001-01-25 |
| HUP0202379A2 (hu) | 2002-12-28 |
| JP4270759B2 (ja) | 2009-06-03 |
| EP1180099A1 (en) | 2002-02-20 |
| NO20015374L (no) | 2001-11-02 |
| HUP0202379A3 (en) | 2003-04-28 |
| WO2000066550A1 (en) | 2000-11-09 |
| MXPA01011043A (es) | 2002-06-04 |
| TR200103144T2 (tr) | 2004-11-22 |
| CA2371215A1 (en) | 2000-11-09 |
| ZA200108967B (en) | 2003-01-30 |
| US20060079484A1 (en) | 2006-04-13 |
| SK15662001A3 (sk) | 2002-09-10 |
| EE200100573A (et) | 2003-02-17 |
| US7423012B2 (en) | 2008-09-09 |
| CN1358187A (zh) | 2002-07-10 |
| AU4447100A (en) | 2000-11-17 |
| BR0010256A (pt) | 2002-02-13 |
| SE9901572D0 (sv) | 1999-05-03 |
| ZA200108966B (en) | 2003-01-30 |
| JP2002543179A (ja) | 2002-12-17 |
| HK1042493A1 (zh) | 2002-08-16 |
| AR028826A1 (es) | 2003-05-28 |
| IL145953A0 (en) | 2002-11-10 |
| IS6141A (is) | 2001-11-01 |
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