NO862373L - Fremgangsmaate for fremstilling av terapeutisk aktive tienopyridoner. - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive tienopyridoner.Info
- Publication number
- NO862373L NO862373L NO862373A NO862373A NO862373L NO 862373 L NO862373 L NO 862373L NO 862373 A NO862373 A NO 862373A NO 862373 A NO862373 A NO 862373A NO 862373 L NO862373 L NO 862373L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- give
- methyl
- mixture
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 48
- 238000002360 preparation method Methods 0.000 title claims description 10
- 230000001225 therapeutic effect Effects 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 176
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 150000001340 alkali metals Chemical class 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- LXZSEJASWJASBC-UHFFFAOYSA-N 4-methyl-6-methylsulfonylthieno[3,2-b]pyridin-7-one Chemical compound CN1C=C(S(C)(=O)=O)C(=O)C2=C1C=CS2 LXZSEJASWJASBC-UHFFFAOYSA-N 0.000 claims description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- 239000000203 mixture Substances 0.000 description 80
- 239000000243 solution Substances 0.000 description 55
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 30
- -1 methoxy, ethoxy, phenyl Chemical group 0.000 description 28
- 239000011928 denatured alcohol Substances 0.000 description 24
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 23
- 239000012265 solid product Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 238000001914 filtration Methods 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 17
- 159000000000 sodium salts Chemical class 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 229940125670 thienopyridine Drugs 0.000 description 14
- 239000002175 thienopyridine Substances 0.000 description 14
- 239000012258 stirred mixture Substances 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 11
- 230000036772 blood pressure Effects 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 11
- FONCNASJEUIDPE-UHFFFAOYSA-N methyl 3-hydroxy-2-methylsulfanylprop-2-enoate Chemical compound COC(=O)C(SC)=CO FONCNASJEUIDPE-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 238000009835 boiling Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- DLEBOPPNWGZOHU-UHFFFAOYSA-N 4-methyl-6-methylsulfinylthieno[3,2-b]pyridin-7-one Chemical compound CN1C=C(S(C)=O)C(=O)C2=C1C=CS2 DLEBOPPNWGZOHU-UHFFFAOYSA-N 0.000 description 4
- FOPVYSVQCZHLIN-UHFFFAOYSA-N CC(C=CN=C1C2=O)C1=C[S+]2S(C)=O Chemical compound CC(C=CN=C1C2=O)C1=C[S+]2S(C)=O FOPVYSVQCZHLIN-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- GKFLKOFXONRIGL-UHFFFAOYSA-N 2-(2-chlorophenyl)-4-methyl-6-methylsulfanylthieno[3,2-b]pyridin-7-one Chemical compound S1C=2C(=O)C(SC)=CN(C)C=2C=C1C1=CC=CC=C1Cl GKFLKOFXONRIGL-UHFFFAOYSA-N 0.000 description 3
- GLNQOCYQFVHIAC-UHFFFAOYSA-N 6-methylsulfanyl-4h-thieno[3,2-b]pyridin-7-one Chemical compound CSC1=CN=C2C=CSC2=C1O GLNQOCYQFVHIAC-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000004967 organic peroxy acids Chemical class 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
- BQGLRKFKFQRAHF-UHFFFAOYSA-N (5-diazonio-3-iminothiophen-2-ylidene)-methoxymethanolate Chemical compound COC(=O)C=1SC([N+]#N)=CC=1[NH-] BQGLRKFKFQRAHF-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FBNNKCQKPBXLEO-UHFFFAOYSA-N 2,4-dimethyl-6-methylsulfanylthieno[3,2-b]pyridin-7-one Chemical compound O=C1C(SC)=CN(C)C2=C1SC(C)=C2 FBNNKCQKPBXLEO-UHFFFAOYSA-N 0.000 description 2
- HULNYUGHDJWNNB-UHFFFAOYSA-N 2-(2-chlorophenyl)-4-methyl-6-methylsulfinylthieno[3,2-b]pyridin-7-one Chemical compound C=1C=2N(C)C=C(S(C)=O)C(=O)C=2SC=1C1=CC=CC=C1Cl HULNYUGHDJWNNB-UHFFFAOYSA-N 0.000 description 2
- UJQZFMIHWWTZBJ-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-methyl-6-methylsulfanylthieno[3,2-b]pyridin-7-one Chemical compound S1C=2C(=O)C(SC)=CN(C)C=2C=C1C1=CC=CC(Cl)=C1 UJQZFMIHWWTZBJ-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- DSOBSDOBPZNWNW-UHFFFAOYSA-N 3-[(3-methoxy-2-methylsulfanyl-3-oxoprop-1-enyl)amino]thiophene-2-carboxylic acid Chemical compound COC(=O)C(SC)=CNC=1C=CSC=1C(O)=O DSOBSDOBPZNWNW-UHFFFAOYSA-N 0.000 description 2
- UZRWOWQXQWKNNQ-UHFFFAOYSA-N 3-ethoxy-4-methyl-6-methylsulfanylthieno[3,2-b]pyridin-7-one Chemical compound CN1C=C(SC)C(=O)C2=C1C(OCC)=CS2 UZRWOWQXQWKNNQ-UHFFFAOYSA-N 0.000 description 2
- QMYWZMDZCWCYNH-UHFFFAOYSA-N 3-ethoxy-4-methyl-6-methylsulfinylthieno[3,2-b]pyridin-7-one Chemical compound CN1C=C(S(C)=O)C(=O)C2=C1C(OCC)=CS2 QMYWZMDZCWCYNH-UHFFFAOYSA-N 0.000 description 2
- SWALGAGZRWJLCT-UHFFFAOYSA-N 4-methyl-6-(methylsulfonylmethyl)thieno[3,2-b]pyridin-7-one Chemical compound CN1C=C(CS(C)(=O)=O)C(=O)C2=C1C=CS2 SWALGAGZRWJLCT-UHFFFAOYSA-N 0.000 description 2
- LBSXHVXQBYKMOQ-UHFFFAOYSA-N 4-methyl-6-methylsulfanyl-2-phenylthieno[3,2-b]pyridin-7-one Chemical compound S1C=2C(=O)C(SC)=CN(C)C=2C=C1C1=CC=CC=C1 LBSXHVXQBYKMOQ-UHFFFAOYSA-N 0.000 description 2
- PVQJJFKLQGNQMX-UHFFFAOYSA-N 4-methyl-6-methylsulfanylthieno[3,2-b]pyridin-7-one Chemical compound O=C1C(SC)=CN(C)C2=C1SC=C2 PVQJJFKLQGNQMX-UHFFFAOYSA-N 0.000 description 2
- SHTOXVMZRVPLBW-UHFFFAOYSA-N 4-methyl-6-methylsulfinyl-2-phenylthieno[3,2-b]pyridin-7-one Chemical compound C=1C=2N(C)C=C(S(C)=O)C(=O)C=2SC=1C1=CC=CC=C1 SHTOXVMZRVPLBW-UHFFFAOYSA-N 0.000 description 2
- AACVULYSNJAKEQ-UHFFFAOYSA-N 4h-thieno[3,2-b]pyridin-7-one Chemical compound OC1=CC=NC2=C1SC=C2 AACVULYSNJAKEQ-UHFFFAOYSA-N 0.000 description 2
- SIFNGOZBWWIMRR-UHFFFAOYSA-N 7-methyl-5-methylsulfanylthieno[2,3-b]pyridin-4-one Chemical compound O=C1C(SC)=CN(C)C2=C1C=CS2 SIFNGOZBWWIMRR-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- VBRNRDNUFZHVMD-UHFFFAOYSA-N CC(C=CN=C1C2=O)C1=C[S+]2SC Chemical compound CC(C=CN=C1C2=O)C1=C[S+]2SC VBRNRDNUFZHVMD-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 239000000538 analytical sample Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- KYIZHMXFNFGGHA-UHFFFAOYSA-N cis-beta-Chlor-alpha-phenyl-acrylnitril Natural products ClC=C(C#N)C1=CC=CC=C1 KYIZHMXFNFGGHA-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 2
- TWEQNZZOOFKOER-UHFFFAOYSA-N methyl 3-aminothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1N TWEQNZZOOFKOER-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 230000010349 pulsation Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- SMZMHUCIDGHERP-UHFFFAOYSA-N thieno[2,3-b]pyridine Chemical compound C1=CN=C2SC=CC2=C1 SMZMHUCIDGHERP-UHFFFAOYSA-N 0.000 description 2
- FKNKKPFULFAZLX-UHFFFAOYSA-N thieno[3,4-b]pyridine Chemical compound N1=CC=CC2=CSC=C21 FKNKKPFULFAZLX-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 150000003577 thiophenes Chemical class 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- ZDOYHCIRUPHUHN-UHFFFAOYSA-N 1-(2-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1Cl ZDOYHCIRUPHUHN-UHFFFAOYSA-N 0.000 description 1
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- 239000010452 phosphate Substances 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- WPEFWEIHTOLOLC-UHFFFAOYSA-M sodium;3-amino-5-methylthiophene-2-carboxylate Chemical compound [Na+].CC1=CC(N)=C(C([O-])=O)S1 WPEFWEIHTOLOLC-UHFFFAOYSA-M 0.000 description 1
- WVMADKBGYOAZKM-UHFFFAOYSA-M sodium;3-aminothiophene-2-carboxylate Chemical compound [Na+].NC=1C=CSC=1C([O-])=O WVMADKBGYOAZKM-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YCBIOFDKORLEPZ-UHFFFAOYSA-N thieno[2,3-b]pyridine 1-oxide Chemical class C1=CN=C2S(=O)C=CC2=C1 YCBIOFDKORLEPZ-UHFFFAOYSA-N 0.000 description 1
- PLFPURRZLGMMCI-UHFFFAOYSA-N thieno[3,2-b]pyridine 1-oxide Chemical class C1=CC=C2S(=O)C=CC2=N1 PLFPURRZLGMMCI-UHFFFAOYSA-N 0.000 description 1
- GWNZXHGUNFBXNX-UHFFFAOYSA-N thieno[3,4-b]pyridine 6-oxide Chemical class C1=CC=NC2=CS(=O)C=C21 GWNZXHGUNFBXNX-UHFFFAOYSA-N 0.000 description 1
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
- UIERETOOQGIECD-ONEGZZNKSA-N tiglic acid Chemical compound C\C=C(/C)C(O)=O UIERETOOQGIECD-ONEGZZNKSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB858515207A GB8515207D0 (en) | 1985-06-15 | 1985-06-15 | Therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO862373D0 NO862373D0 (no) | 1986-06-13 |
| NO862373L true NO862373L (no) | 1986-12-16 |
Family
ID=10580803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO862373A NO862373L (no) | 1985-06-15 | 1986-06-13 | Fremgangsmaate for fremstilling av terapeutisk aktive tienopyridoner. |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4710506A (da) |
| EP (1) | EP0209977A3 (da) |
| JP (1) | JPS6236382A (da) |
| KR (1) | KR870000339A (da) |
| AU (1) | AU581595B2 (da) |
| CS (1) | CS258483B2 (da) |
| DD (1) | DD253823A5 (da) |
| DK (1) | DK272486A (da) |
| ES (1) | ES8707243A1 (da) |
| FI (1) | FI862520A (da) |
| GB (1) | GB8515207D0 (da) |
| GR (1) | GR861527B (da) |
| HU (1) | HU195661B (da) |
| JO (1) | JO1482B1 (da) |
| NO (1) | NO862373L (da) |
| PH (1) | PH22293A (da) |
| PL (1) | PL266392A1 (da) |
| PT (1) | PT82759B (da) |
| YU (2) | YU99386A (da) |
| ZA (1) | ZA864396B (da) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8627698D0 (en) * | 1986-11-20 | 1986-12-17 | Boots Co Plc | Therapeutic agents |
| US4767766A (en) * | 1987-01-30 | 1988-08-30 | Merck & Co., Inc. | Derivatives of 3-hydroxyazabenzo(B)thiophene useful as 5-lipoxygenase inhibitors |
| US4904672A (en) * | 1987-01-30 | 1990-02-27 | Merck & Co., Inc. | Derivatives of 3-hydroxyazabenzo[b]thiophene useful as 5-lipoxygenase inhibitors |
| NZ230711A (en) * | 1988-09-23 | 1990-10-26 | Ortho Pharma Corp | Substituted thienopyrans as antihypertensive agents |
| AU5509099A (en) * | 1998-08-03 | 2000-02-28 | Basf Corporation | Pyridinones for the treatment of sexual dysfunction |
| US6458804B1 (en) * | 2001-01-26 | 2002-10-01 | R.T. Alamo Venturesi, Llc | Methods for the treatment of central nervous system disorders in certain patient groups |
| US6451813B1 (en) | 2001-01-26 | 2002-09-17 | R. T. Alamo Ventures I, Llc | Treatment of gastroparesis in certain patient groups |
| US6562838B2 (en) | 2001-01-26 | 2003-05-13 | R. T. Alamo Ventures I, L.L.C. | Treatment of cardiovascular disease with quinolinone enantiomers |
| US8329924B2 (en) * | 2001-06-11 | 2012-12-11 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
| CN101624391A (zh) * | 2001-06-11 | 2010-01-13 | 病毒化学医药公司 | 用作黄病毒感染抗病毒剂的噻吩衍生物 |
| US6995171B2 (en) * | 2001-06-21 | 2006-02-07 | Agouron Pharmaceuticals, Inc. | Bicyclic pyrimidine and pyrimidine derivatives useful as anticancer agents |
| CN100413861C (zh) * | 2002-12-10 | 2008-08-27 | 维勒凯姆制药股份有限公司 | 用于治疗或预防黄病毒感染的化合物 |
| US7994192B2 (en) * | 2006-09-26 | 2011-08-09 | Crestone, Inc. | Substituted thienopyridone compounds with antibacterial activity |
| US8697720B2 (en) | 2006-09-26 | 2014-04-15 | Crestone, Inc. | Substituted phenylether-thienopyridone compounds with antibacterial activity |
| US7973050B2 (en) * | 2006-09-26 | 2011-07-05 | Crestone, Inc. | Enantiomeric compounds with antibacterial activity |
| US8658670B2 (en) * | 2006-09-26 | 2014-02-25 | Crestone, Inc. | Methods and compounds for treatment of clostridium based infection |
| ES2392897T3 (es) * | 2006-09-26 | 2012-12-14 | Crestone, Inc. | Compuestos tienopiridona sustituidos con actividad antibacteriana |
| EP2559692A1 (en) | 2006-11-15 | 2013-02-20 | Virochem Pharma Inc. | Thiophene analogues for the treatment or prevention of Flavivirus infections |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3997545A (en) * | 1973-07-23 | 1976-12-14 | Takeda Chemical Industries, Ltd. | Thienopyridine-carboxylic acid derivatives |
| NZ193167A (en) * | 1979-03-27 | 1984-08-24 | Boots Co Plc | Quinoline derivatives and pharmaceutical compositions |
| JPS5742690A (en) * | 1980-08-28 | 1982-03-10 | Kanebo Ltd | Thieno 3,2-b pyridinecarboxylic acid derivative |
| GB2085441B (en) * | 1980-09-26 | 1984-10-17 | Boots The Co Ltd | Therapeutic agents |
| IE51542B1 (en) * | 1980-09-26 | 1987-01-07 | Boots Co Ltd | Therapeutic agents |
| DE3412947A1 (de) * | 1984-04-06 | 1985-10-17 | Bayer Ag, 5090 Leverkusen | Tetrahydothienopyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
-
1985
- 1985-06-15 GB GB858515207A patent/GB8515207D0/en active Pending
-
1986
- 1986-06-05 AU AU58383/86A patent/AU581595B2/en not_active Expired - Fee Related
- 1986-06-09 PH PH33869A patent/PH22293A/en unknown
- 1986-06-09 EP EP86304382A patent/EP0209977A3/en not_active Withdrawn
- 1986-06-10 DK DK272486A patent/DK272486A/da not_active Application Discontinuation
- 1986-06-10 YU YU00993/86A patent/YU99386A/xx unknown
- 1986-06-12 PT PT82759A patent/PT82759B/pt unknown
- 1986-06-12 FI FI862520A patent/FI862520A/fi not_active Application Discontinuation
- 1986-06-12 ZA ZA864396A patent/ZA864396B/xx unknown
- 1986-06-12 GR GR861527A patent/GR861527B/el unknown
- 1986-06-12 CS CS864362A patent/CS258483B2/cs unknown
- 1986-06-13 US US06/874,337 patent/US4710506A/en not_active Expired - Lifetime
- 1986-06-13 DD DD86291289A patent/DD253823A5/de unknown
- 1986-06-13 ES ES556026A patent/ES8707243A1/es not_active Expired
- 1986-06-13 HU HU862521A patent/HU195661B/hu not_active IP Right Cessation
- 1986-06-13 NO NO862373A patent/NO862373L/no unknown
- 1986-06-14 KR KR1019860004737A patent/KR870000339A/ko not_active Application Discontinuation
- 1986-06-14 JO JO19861482A patent/JO1482B1/en active
- 1986-06-16 PL PL1986266392A patent/PL266392A1/xx unknown
- 1986-06-16 JP JP61139953A patent/JPS6236382A/ja active Pending
-
1987
- 1987-06-29 YU YU01211/87A patent/YU121187A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CS436286A2 (en) | 1987-12-17 |
| DK272486D0 (da) | 1986-06-10 |
| JPS6236382A (ja) | 1987-02-17 |
| EP0209977A2 (en) | 1987-01-28 |
| HUT42775A (en) | 1987-08-28 |
| ES8707243A1 (es) | 1987-07-16 |
| GB8515207D0 (en) | 1985-07-17 |
| CS258483B2 (en) | 1988-08-16 |
| ZA864396B (en) | 1987-08-26 |
| FI862520A0 (fi) | 1986-06-12 |
| NO862373D0 (no) | 1986-06-13 |
| EP0209977A3 (en) | 1988-06-08 |
| HU195661B (en) | 1988-06-28 |
| AU581595B2 (en) | 1989-02-23 |
| DD253823A5 (de) | 1988-02-03 |
| FI862520A (fi) | 1986-12-16 |
| US4710506A (en) | 1987-12-01 |
| PL266392A1 (en) | 1988-02-18 |
| GR861527B (en) | 1986-10-14 |
| KR870000339A (ko) | 1987-02-17 |
| YU99386A (en) | 1988-04-30 |
| AU5838386A (en) | 1986-12-18 |
| JO1482B1 (en) | 1988-03-10 |
| YU121187A (en) | 1988-04-30 |
| PT82759A (en) | 1986-07-01 |
| PH22293A (en) | 1988-07-22 |
| DK272486A (da) | 1986-12-16 |
| ES556026A0 (es) | 1987-07-16 |
| PT82759B (en) | 1988-05-12 |
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