NO321377B1 - Nye forbindelser - Google Patents
Nye forbindelser Download PDFInfo
- Publication number
- NO321377B1 NO321377B1 NO20015383A NO20015383A NO321377B1 NO 321377 B1 NO321377 B1 NO 321377B1 NO 20015383 A NO20015383 A NO 20015383A NO 20015383 A NO20015383 A NO 20015383A NO 321377 B1 NO321377 B1 NO 321377B1
- Authority
- NO
- Norway
- Prior art keywords
- tert
- mmol
- pyridin
- amino
- added
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 145
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 102
- -1 aminopyridyl group Chemical group 0.000 claims description 46
- 239000002253 acid Substances 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 27
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 108090000201 Carboxypeptidase B2 Proteins 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 102000003847 Carboxypeptidase B2 Human genes 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 239000003112 inhibitor Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 7
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 claims description 4
- DKLMDFWCRUWOSL-UHFFFAOYSA-N 3-piperidin-4-yl-2-(sulfanylmethyl)butanoic acid Chemical compound SCC(C(O)=O)C(C)C1CCNCC1 DKLMDFWCRUWOSL-UHFFFAOYSA-N 0.000 claims description 3
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 claims description 3
- 102000007466 Purinergic P2 Receptors Human genes 0.000 claims description 3
- 108010085249 Purinergic P2 Receptors Proteins 0.000 claims description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 102000003938 Thromboxane Receptors Human genes 0.000 claims description 3
- 108090000300 Thromboxane Receptors Proteins 0.000 claims description 3
- 239000005557 antagonist Substances 0.000 claims description 3
- 239000003146 anticoagulant agent Substances 0.000 claims description 3
- 229940127218 antiplatelet drug Drugs 0.000 claims description 3
- 229960004676 antithrombotic agent Drugs 0.000 claims description 3
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000002319 fibrinogen receptor antagonist Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 239000003999 initiator Substances 0.000 claims description 3
- 230000010534 mechanism of action Effects 0.000 claims description 3
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 3
- 150000003815 prostacyclins Chemical class 0.000 claims description 3
- QCFBHSCPFQJTRX-UHFFFAOYSA-N 2-(piperazin-1-ylmethyl)-3-sulfanylpropanoic acid Chemical compound OC(=O)C(CS)CN1CCNCC1 QCFBHSCPFQJTRX-UHFFFAOYSA-N 0.000 claims description 2
- ZYVSJXROQJSTDA-UHFFFAOYSA-N 2-(piperidin-4-ylmethyl)-3-sulfanylpropanoic acid Chemical compound OC(=O)C(CS)CC1CCNCC1 ZYVSJXROQJSTDA-UHFFFAOYSA-N 0.000 claims description 2
- HDTSLVJNIQOOLA-UHFFFAOYSA-N 2-[(1-acetylpiperidin-4-yl)methyl]-3-sulfanylpropanoic acid Chemical compound CC(=O)N1CCC(CC(CS)C(O)=O)CC1 HDTSLVJNIQOOLA-UHFFFAOYSA-N 0.000 claims description 2
- APAFTGBGIRHBQC-UHFFFAOYSA-N 2-[(2-amino-1,3-thiazol-5-yl)methyl]-3-sulfanylpropanoic acid Chemical compound NC1=NC=C(CC(CS)C(O)=O)S1 APAFTGBGIRHBQC-UHFFFAOYSA-N 0.000 claims description 2
- FQKZXZOZDCPEQN-UHFFFAOYSA-N 2-[(6-amino-5-chloropyridin-3-yl)methyl]-3-sulfanylpropanoic acid Chemical compound NC1=NC=C(CC(CS)C(O)=O)C=C1Cl FQKZXZOZDCPEQN-UHFFFAOYSA-N 0.000 claims description 2
- ZBBLYHBYJXJMRX-UHFFFAOYSA-N 2-[(6-amino-5-methylpyridin-3-yl)methyl]-3-sulfanylpropanoic acid Chemical compound CC1=CC(CC(CS)C(O)=O)=CN=C1N ZBBLYHBYJXJMRX-UHFFFAOYSA-N 0.000 claims description 2
- BBQCDPWTTKUXAP-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-2-(sulfanylmethyl)butanoic acid Chemical compound CCC(CS)(C(O)=O)CC1=CC=C(N)N=C1 BBQCDPWTTKUXAP-UHFFFAOYSA-N 0.000 claims description 2
- OTZWVYSKISQVDL-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-2-methyl-3-sulfanylpropanoic acid Chemical compound SCC(C)(C(O)=O)CC1=CC=C(N)N=C1 OTZWVYSKISQVDL-UHFFFAOYSA-N 0.000 claims description 2
- ARYOFLBXDDTAEO-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-3-sulfanylpentanoic acid Chemical compound CCC(S)C(C(O)=O)CC1=CC=C(N)N=C1 ARYOFLBXDDTAEO-UHFFFAOYSA-N 0.000 claims description 2
- VYLXBPDZIRSBPV-UHFFFAOYSA-N 3-(6-aminopyridin-3-yl)-2-(sulfanylmethyl)hexanoic acid Chemical compound CCCC(C(CS)C(O)=O)C1=CC=C(N)N=C1 VYLXBPDZIRSBPV-UHFFFAOYSA-N 0.000 claims description 2
- SOUYBVCPFHGOIJ-UHFFFAOYSA-N 5-methyl-2-(piperidin-4-ylmethyl)-3-sulfanylhexanoic acid Chemical compound CC(C)CC(S)C(C(O)=O)CC1CCNCC1 SOUYBVCPFHGOIJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 5
- 102000003960 Ligases Human genes 0.000 claims 2
- 108090000364 Ligases Proteins 0.000 claims 2
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims 2
- SONFPPSNMCSISZ-UHFFFAOYSA-N 2-[(6-amino-4-methylpyridin-3-yl)methyl]-3-sulfanylpropanoic acid Chemical compound CC1=CC(N)=NC=C1CC(CS)C(O)=O SONFPPSNMCSISZ-UHFFFAOYSA-N 0.000 claims 1
- ZTHVRWJTWHUJHD-UHFFFAOYSA-N 2-[(6-amino-5-methylpyridin-3-yl)methyl]-2-methyl-3-sulfanylpropanoic acid Chemical compound CC1=CC(CC(C)(CS)C(O)=O)=CN=C1N ZTHVRWJTWHUJHD-UHFFFAOYSA-N 0.000 claims 1
- KDYLKSWVJIFALL-UHFFFAOYSA-N 2-[(6-aminopyridin-3-yl)methyl]-3-sulfanylpropanoic acid Chemical compound NC1=CC=C(CC(CS)C(O)=O)C=N1 KDYLKSWVJIFALL-UHFFFAOYSA-N 0.000 claims 1
- QRAJKOYCAQBLBC-UHFFFAOYSA-N 3-(6-aminopyridin-3-yl)-2-(sulfanylmethyl)butanoic acid Chemical compound SCC(C(O)=O)C(C)C1=CC=C(N)N=C1 QRAJKOYCAQBLBC-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 303
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 279
- 239000000243 solution Substances 0.000 description 238
- 239000000203 mixture Substances 0.000 description 232
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 185
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 146
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 142
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 132
- 235000019439 ethyl acetate Nutrition 0.000 description 126
- 239000011541 reaction mixture Substances 0.000 description 124
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 114
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 109
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 94
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 76
- 239000000460 chlorine Substances 0.000 description 75
- 239000012267 brine Substances 0.000 description 71
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 71
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 69
- 238000003818 flash chromatography Methods 0.000 description 68
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
- 229910052786 argon Inorganic materials 0.000 description 66
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 60
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 60
- 150000002148 esters Chemical class 0.000 description 54
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 53
- 239000012043 crude product Substances 0.000 description 52
- 239000012044 organic layer Substances 0.000 description 49
- 239000012074 organic phase Substances 0.000 description 49
- 238000005481 NMR spectroscopy Methods 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- 229920006395 saturated elastomer Polymers 0.000 description 41
- 238000003756 stirring Methods 0.000 description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 30
- 239000000725 suspension Substances 0.000 description 29
- 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 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 28
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 27
- 239000010410 layer Substances 0.000 description 27
- 229940086542 triethylamine Drugs 0.000 description 26
- 238000001914 filtration Methods 0.000 description 25
- 229910000104 sodium hydride Inorganic materials 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 21
- 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 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 17
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 17
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 16
- 239000005457 ice water Substances 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 15
- 125000004494 ethyl ester group Chemical group 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- CNJLVGGYAPLKSK-UHFFFAOYSA-N ethyl 3-acetylsulfanyl-2-[[6-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-3-yl]methyl]butanoate Chemical compound CCOC(=O)C(C(C)SC(C)=O)CC1=CC=C(NC(=O)OC(C)(C)C)N=C1 CNJLVGGYAPLKSK-UHFFFAOYSA-N 0.000 description 14
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 14
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 12
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 102000013566 Plasminogen Human genes 0.000 description 8
- 108010051456 Plasminogen Proteins 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 230000020764 fibrinolysis Effects 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 8
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 229960001701 chloroform Drugs 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- 235000019260 propionic acid Nutrition 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
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- 230000035484 reaction time Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229910052707 ruthenium Inorganic materials 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
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
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- 239000007858 starting material Substances 0.000 description 1
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- 229960005202 streptokinase Drugs 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JJHVUCZETPMUQH-UHFFFAOYSA-N tert-butyl 2-(acetylsulfanylmethyl)-2-methyl-3-[6-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-3-yl]propanoate Chemical compound CC(=O)SCC(C)(C(=O)OC(C)(C)C)CC1=CC=C(NC(=O)OC(C)(C)C)N=C1 JJHVUCZETPMUQH-UHFFFAOYSA-N 0.000 description 1
- XMNCGYHYYHDHEK-UHFFFAOYSA-N tert-butyl 3-(trifluoromethylsulfonyloxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(COS(=O)(=O)C(F)(F)F)C1 XMNCGYHYYHDHEK-UHFFFAOYSA-N 0.000 description 1
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
- GSDWIYMZFDFEHB-UHFFFAOYSA-N tert-butyl 4-[2-(acetylsulfanylmethyl)-3-ethoxy-3-oxopropyl]piperazine-1-carboxylate Chemical compound CCOC(=O)C(CSC(C)=O)CN1CCN(C(=O)OC(C)(C)C)CC1 GSDWIYMZFDFEHB-UHFFFAOYSA-N 0.000 description 1
- BRGVPNLOCJBSAP-UHFFFAOYSA-N tert-butyl 4-[3-[(4-methoxyphenyl)methylsulfanyl]-2-[(2-methylpropan-2-yl)oxycarbonyl]-4-phenylbutyl]piperidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1CSC(C(CC1CCN(CC1)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)CC1=CC=CC=C1 BRGVPNLOCJBSAP-UHFFFAOYSA-N 0.000 description 1
- JIXGVTKDMZLHBA-UHFFFAOYSA-N tert-butyl 5-(2-ethoxycarbonyl-4-methylpent-1-en-3-yl)pyridine-2-carboxylate Chemical compound CCOC(=O)C(=C)C(C(C)C)C1=CC=C(C(=O)OC(C)(C)C)N=C1 JIXGVTKDMZLHBA-UHFFFAOYSA-N 0.000 description 1
- SBRXAMDDQXWBNU-UHFFFAOYSA-N tert-butyl N-[5-(2-tert-butylsilyloxypropan-2-yl)pyrimidin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound C(C)(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=NC=C(C=N1)C(O[SiH2]C(C)(C)C)(C)C SBRXAMDDQXWBNU-UHFFFAOYSA-N 0.000 description 1
- IRCGDNMIKIGMJT-UHFFFAOYSA-N tert-butyl n-(5-bromo-4-methylpyridin-2-yl)-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC1=CC(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=NC=C1Br IRCGDNMIKIGMJT-UHFFFAOYSA-N 0.000 description 1
- GDKYABNFMXOTAN-UHFFFAOYSA-N tert-butyl n-(5-bromopyrimidin-2-yl)-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=NC=C(Br)C=N1 GDKYABNFMXOTAN-UHFFFAOYSA-N 0.000 description 1
- BAFFUZOICRQKTQ-UHFFFAOYSA-N tert-butyl n-(5-hydroxy-6-methylpyridin-2-yl)carbamate Chemical compound CC1=NC(NC(=O)OC(C)(C)C)=CC=C1O BAFFUZOICRQKTQ-UHFFFAOYSA-N 0.000 description 1
- MVIWPMBRXBNBDX-DTWKUNHWSA-N tert-butyl n-[(1s,4r)-4-(hydroxymethyl)cyclopent-2-en-1-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1C[C@@H](CO)C=C1 MVIWPMBRXBNBDX-DTWKUNHWSA-N 0.000 description 1
- APLGUKPUXMWCPP-UHFFFAOYSA-N tert-butyl n-[3-ethenyl-5-(hydroxymethyl)pyridin-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=NC=C(CO)C=C1C=C APLGUKPUXMWCPP-UHFFFAOYSA-N 0.000 description 1
- TWFAMEOZPYPOIV-UHFFFAOYSA-N tert-butyl n-[4-(bromomethyl)pyridin-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(CBr)=CC=N1 TWFAMEOZPYPOIV-UHFFFAOYSA-N 0.000 description 1
- FDYYJRZBBAAOGW-UHFFFAOYSA-N tert-butyl n-[5-(bromomethyl)-6-methylpyridin-2-yl]carbamate Chemical compound CC1=NC(NC(=O)OC(C)(C)C)=CC=C1CBr FDYYJRZBBAAOGW-UHFFFAOYSA-N 0.000 description 1
- IJVHEEWVQYQBBN-UHFFFAOYSA-N tert-butyl n-[5-(bromomethyl)pyrimidin-2-yl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=NC=C(CBr)C=N1 IJVHEEWVQYQBBN-UHFFFAOYSA-N 0.000 description 1
- UREWGCMDFNIRIV-UHFFFAOYSA-N tert-butyl n-[5-(hydroxymethyl)-4-methylpyridin-2-yl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC1=CC(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=NC=C1CO UREWGCMDFNIRIV-UHFFFAOYSA-N 0.000 description 1
- KIYXIGMBBMTGEB-UHFFFAOYSA-N tert-butyl n-[5-(hydroxymethyl)-6-methylpyridin-2-yl]carbamate Chemical compound CC1=NC(NC(=O)OC(C)(C)C)=CC=C1CO KIYXIGMBBMTGEB-UHFFFAOYSA-N 0.000 description 1
- TZSKPWMXWYBDFJ-UHFFFAOYSA-N tert-butyl n-[5-[(5-ethyl-2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)methyl]pyridin-2-yl]carbamate Chemical compound C=1C=C(NC(=O)OC(C)(C)C)N=CC=1CC1(CC)C(=O)OC(C)(C)OC1=O TZSKPWMXWYBDFJ-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 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
- 150000003573 thiols Chemical group 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
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-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
- 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
- 238000007631 vascular surgery Methods 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
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- 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
-
- 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
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Use Of Switch Circuits For Exchanges And Methods Of Control Of Multiplex Exchanges (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9901573A SE9901573D0 (sv) | 1999-05-03 | 1999-05-03 | New compounds |
| PCT/SE2000/000834 WO2000066557A1 (fr) | 1999-05-03 | 2000-05-03 | Nouveaux composes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20015383D0 NO20015383D0 (no) | 2001-11-02 |
| NO20015383L NO20015383L (no) | 2001-12-21 |
| NO321377B1 true NO321377B1 (no) | 2006-05-02 |
Family
ID=20415426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20015383A NO321377B1 (no) | 1999-05-03 | 2001-11-02 | Nye forbindelser |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US7071175B1 (fr) |
| EP (1) | EP1180098A1 (fr) |
| JP (1) | JP2002543184A (fr) |
| KR (1) | KR100755152B1 (fr) |
| CN (1) | CN1263739C (fr) |
| AR (1) | AR034241A1 (fr) |
| AU (1) | AU771760B2 (fr) |
| BR (1) | BR0010257A (fr) |
| CA (1) | CA2371213C (fr) |
| CZ (1) | CZ20013930A3 (fr) |
| EE (1) | EE04490B1 (fr) |
| HK (1) | HK1042303A1 (fr) |
| HU (1) | HUP0202876A3 (fr) |
| IL (1) | IL145954A0 (fr) |
| IS (1) | IS6139A (fr) |
| MX (1) | MXPA01011055A (fr) |
| MY (1) | MY128014A (fr) |
| NO (1) | NO321377B1 (fr) |
| NZ (1) | NZ515062A (fr) |
| PL (1) | PL200932B1 (fr) |
| RU (1) | RU2244708C2 (fr) |
| SE (1) | SE9901573D0 (fr) |
| SK (1) | SK15462001A3 (fr) |
| TR (1) | TR200103153T2 (fr) |
| TW (1) | TWI232105B (fr) |
| WO (1) | WO2000066557A1 (fr) |
| ZA (1) | ZA200108968B (fr) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6828566B2 (en) * | 1997-07-22 | 2004-12-07 | Hitachi Ltd | Method and apparatus for specimen fabrication |
| SE9901572D0 (sv) * | 1999-05-03 | 1999-05-03 | Astra Ab | New compounds |
| KR100681632B1 (ko) | 1999-09-14 | 2007-02-09 | 메이지 세이카 가이샤 리미티드 | 카르복시펩티다아제 b 저해활성을 갖는 포스폰산 유도체 |
| SE0103272D0 (sv) | 2001-09-28 | 2001-09-28 | Astrazeneca Ab | Chemical compounds |
| WO2003061653A1 (fr) | 2002-01-22 | 2003-07-31 | Pfizer Limited | Acides 3-(imidazolyl)-2-aminopropanoiques servant d'inhibiteurs tafia pour traiter des maladies thrombotiques |
| US6713496B2 (en) | 2002-01-22 | 2004-03-30 | Pfizer Inc | 3-(imidazolyl)-2-alkoxypropanoic acids |
| EP1497300A2 (fr) * | 2002-03-21 | 2005-01-19 | Schering Aktiengesellschaft | Inhibiteurs de plasma carboxypeptidase b |
| AU2003247390A1 (en) | 2002-05-22 | 2003-12-12 | Errant Gene Therapeutics, Llc. | Histone deacetylase inhibitors based on alphachalcogenmethylcarbonyl compounds |
| SE0201837D0 (sv) * | 2002-06-14 | 2002-06-14 | Astrazeneca Ab | Chemical compounds |
| US7576206B2 (en) | 2003-08-14 | 2009-08-18 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
| US7223745B2 (en) | 2003-08-14 | 2007-05-29 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
| US7468383B2 (en) | 2005-02-11 | 2008-12-23 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
| KR101258331B1 (ko) | 2008-09-11 | 2013-04-26 | 화이자 인코포레이티드 | 헤테로아릴 아미드 유도체 및 글루코키나제 활성화제로서의 그의 용도 |
| NZ592764A (en) | 2008-10-29 | 2012-08-31 | Taisho Pharmaceutical Co Ltd | Compound having tafia inhibitory activity |
| WO2010084428A1 (fr) | 2009-01-20 | 2010-07-29 | Pfizer Inc. | Pyrazinone amides substitués |
| MY151246A (en) | 2009-03-11 | 2014-04-30 | Pfizer | Benzofuranyl derivatives |
| AU2010341530B2 (en) | 2009-12-22 | 2016-03-10 | Cephalon, Inc. | Proteasome inhibitors and processes for their preparation, purification and use |
| CN102249992A (zh) * | 2011-07-05 | 2011-11-23 | 广东工业大学 | 一种制备2-氨基异烟酸的方法 |
| CA3085086C (fr) | 2011-12-06 | 2023-08-08 | Delta Faucet Company | Distribution d'ozone dans un robinet |
| CA2914533A1 (fr) | 2013-06-10 | 2014-12-18 | Sanofi | Derives d'uree macrocycliques utiles en tant qu'inhibiteurs de tafia, leur preparation et leur utilisation en tant que produits pharmaceutiques |
| AR099134A1 (es) * | 2014-01-24 | 2016-06-29 | Hoffmann La Roche | Procedimiento para la preparación de n-[(3-aminooxetán-3-il)metil]-2-(1,1-dioxo-3,5-dihidro-1,4-benzotiazepín-4-il)-6-metil-quinazolín-4-amina |
| CN108463437B (zh) | 2015-12-21 | 2022-07-08 | 德尔塔阀门公司 | 包括消毒装置的流体输送系统 |
| USD879309S1 (en) | 2018-08-09 | 2020-03-24 | Scott Specialties, Inc. | Maternity support |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3091569A (en) | 1960-08-26 | 1963-05-28 | Mead Johnson & Co | Mucolytic-nu-acylated sulfhydryl compositions and process for treating animal mucus |
| FR1393338A (fr) | 1964-01-08 | 1965-03-26 | Rech S Pharma Et Scient | Nouveau dérivé de la cystéine et sa préparation |
| US3766206A (en) | 1971-11-03 | 1973-10-16 | Pfizer | 18beta-glycyrrheting acid amides useful as antiulcer agents |
| FR2266502A1 (en) | 1974-04-08 | 1975-10-31 | Synpharm Sa | N-(2-thenoyl)-cysteine and esters - with mucolytic activity, prepd. from cysteine (esters) and thenoyl chloride |
| US4177277A (en) | 1977-01-17 | 1979-12-04 | E. R. Squibb & Sons, Inc. | Method for alleviating hypertension |
| US4113715A (en) | 1977-01-17 | 1978-09-12 | E. R. Squibb & Sons, Inc. | Amino acid derivatives |
| JPS545949A (en) | 1977-06-16 | 1979-01-17 | Hisamitsu Pharmaceut Co Inc | Novel cyclohexanecarboxylic acid and its derivatives |
| FR2430945A2 (fr) | 1978-07-12 | 1980-02-08 | Chauvin Blache Lab | Nouveaux derives de la cysteine, leur procede de fabrication et leur application en therapeutique |
| US4537727A (en) | 1982-11-12 | 1985-08-27 | Eli Lilly And Company | Process for recovering 2-acetylthiomethyl-5-aminopentanoic acid |
| DE3467754D1 (de) * | 1983-10-03 | 1988-01-07 | Squibb & Sons Inc | Enkephalinase inhibitors |
| WO1986004580A1 (fr) * | 1985-02-08 | 1986-08-14 | Takeda Chemical Industries, Ltd. | Derives de piperidine |
| US4708965A (en) | 1985-09-16 | 1987-11-24 | Morgan Lee R | Method of treating herpes virus infections with N,N'-diacetylcystine and derivatives |
| JPS62270555A (ja) * | 1986-05-19 | 1987-11-24 | Dainippon Pharmaceut Co Ltd | スルホン酸誘導体およびその塩 |
| EP0318859A3 (fr) | 1987-12-03 | 1990-08-16 | Dainippon Pharmaceutical Co., Ltd. | Dérivés N-substitués de mercaptopropionamide |
| JPH01254654A (ja) * | 1988-04-01 | 1989-10-11 | Dainippon Pharmaceut Co Ltd | スルホン酸の誘導体及びその塩 |
| EP0361365A1 (fr) * | 1988-09-30 | 1990-04-04 | E.R. SQUIBB & SONS, INC. | Composés d'acides aminobenzoiques et aminocyclohexane carboxyliques, compositions, et méthode d'application |
| DE3838467C2 (de) | 1988-11-12 | 1998-12-10 | Agfa Gevaert Ag | Fotografisches Aufzeichnungsmaterial |
| TW230771B (fr) * | 1990-08-09 | 1994-09-21 | Sankyo Co | |
| IT1249650B (it) | 1991-05-29 | 1995-03-09 | Poli Ind Chimica Spa | N-(5-tioxo-l-prolil)-l-cisteina e suoi derivati, loro preparazione ed impiego terapeutico |
| GB9122016D0 (en) * | 1991-10-16 | 1991-11-27 | Glaxo Group Ltd | Chemical compounds |
| IT1266571B1 (it) | 1993-07-30 | 1997-01-09 | Zambon Spa | Derivati della beta-mercapto-propanammide utili nel trattamento delle malattie cardiovascolari |
| US5470834A (en) * | 1993-10-06 | 1995-11-28 | Florida State University | Sulfoximine and suldodiimine matrix metalloproteinase inhibitors |
| DE4441873A1 (de) * | 1994-11-24 | 1996-05-30 | Wella Ag | Mittel zur dauerhaften Haarverformung |
| JP3874455B2 (ja) * | 1996-06-27 | 2007-01-31 | 新日本製鐵株式会社 | フィブリノーゲン受容体拮抗物質およびそれを有効成分とする医薬製剤 |
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