CA1060024A - Thiazoline derivatives and production thereof - Google Patents
Thiazoline derivatives and production thereofInfo
- Publication number
- CA1060024A CA1060024A CA240,770A CA240770A CA1060024A CA 1060024 A CA1060024 A CA 1060024A CA 240770 A CA240770 A CA 240770A CA 1060024 A CA1060024 A CA 1060024A
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- hydrogen
- thiazolin
- phenyl
- ylideneamino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000003549 thiazolines Chemical class 0.000 title claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 title claims abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 70
- 239000001257 hydrogen Substances 0.000 claims abstract description 70
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 51
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 22
- 125000004185 ester group Chemical group 0.000 claims abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 238000003379 elimination reaction Methods 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- 238000005956 quaternization reaction Methods 0.000 claims abstract description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 6
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract 5
- 238000000034 method Methods 0.000 claims description 59
- 150000001875 compounds Chemical class 0.000 claims description 56
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 54
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- -1 alkali metal hydrogencarbonate Chemical class 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 13
- VSAMEASAFWDALV-UHFFFAOYSA-N 2-[2-chloro-4-[(3-methyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound C1=C(Cl)C(C(C(O)=O)C)=CC=C1N=C1N(C)C=CS1 VSAMEASAFWDALV-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 238000006114 decarboxylation reaction Methods 0.000 claims description 5
- UPSSOIHDLUZYKT-UHFFFAOYSA-N 2-[4-[(3-methyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1N=C1N(C)C=CS1 UPSSOIHDLUZYKT-UHFFFAOYSA-N 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 150000003863 ammonium salts Chemical class 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- UTPJKLUKJXJQKN-UHFFFAOYSA-N 2-(3-methyl-2-phenylimino-1,3-thiazol-4-yl)propanoic acid Chemical compound CN1C(C(C(O)=O)C)=CSC1=NC1=CC=CC=C1 UTPJKLUKJXJQKN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical group 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 150000008050 dialkyl sulfates Chemical class 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 9
- PRCWQYFWDDDHRV-UHFFFAOYSA-N 2-[2-chloro-4-[(3,4-dimethyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound C1=C(Cl)C(C(C(O)=O)C)=CC=C1N=C1N(C)C(C)=CS1 PRCWQYFWDDDHRV-UHFFFAOYSA-N 0.000 claims 2
- JOSHLQDNYLKFLI-UHFFFAOYSA-N 2-[3,5-dichloro-4-[(3-methyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound ClC1=CC(C(C(O)=O)C)=CC(Cl)=C1N=C1N(C)C=CS1 JOSHLQDNYLKFLI-UHFFFAOYSA-N 0.000 claims 2
- BTWJNWMUUJGZAD-UHFFFAOYSA-N 2-[3-chloro-4-[(3,4-dimethyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N=C1N(C)C(C)=CS1 BTWJNWMUUJGZAD-UHFFFAOYSA-N 0.000 claims 2
- HWBSPGYVNIILHM-UHFFFAOYSA-N 2-[3-chloro-4-[(3-methyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N=C1N(C)C=CS1 HWBSPGYVNIILHM-UHFFFAOYSA-N 0.000 claims 2
- ZNZLSQFCVWWQKP-UHFFFAOYSA-N 2-[3-chloro-4-[(3-prop-2-enyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N=C1N(CC=C)C=CS1 ZNZLSQFCVWWQKP-UHFFFAOYSA-N 0.000 claims 2
- SRRGIKPPQOGWGA-UHFFFAOYSA-N 2-[3-fluoro-4-[(3-methyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1N=C1N(C)C=CS1 SRRGIKPPQOGWGA-UHFFFAOYSA-N 0.000 claims 2
- OJJCJLLXZOWWSX-UHFFFAOYSA-N 2-[3,5-dichloro-4-[(3,4-dimethyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoic acid Chemical compound ClC1=CC(C(C(O)=O)C)=CC(Cl)=C1N=C1N(C)C(C)=CS1 OJJCJLLXZOWWSX-UHFFFAOYSA-N 0.000 claims 1
- 101100277337 Arabidopsis thaliana DDM1 gene Proteins 0.000 claims 1
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 claims 1
- 101150113676 chr1 gene Proteins 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 4
- 230000003356 anti-rheumatic effect Effects 0.000 abstract description 4
- 239000003435 antirheumatic agent Substances 0.000 abstract description 4
- 239000000730 antalgic agent Substances 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 239000002221 antipyretic Substances 0.000 abstract 1
- 229940125716 antipyretic agent Drugs 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 94
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 30
- 239000000460 chlorine Substances 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 235000019260 propionic acid Nutrition 0.000 description 23
- 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 23
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 239000000203 mixture Substances 0.000 description 16
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229940073584 methylene chloride Drugs 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 229940093956 potassium carbonate Drugs 0.000 description 11
- 239000011575 calcium Substances 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 235000011181 potassium carbonates Nutrition 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- 229960000443 hydrochloric acid Drugs 0.000 description 7
- 235000011167 hydrochloric acid Nutrition 0.000 description 7
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 235000011118 potassium hydroxide Nutrition 0.000 description 6
- 229940093932 potassium hydroxide Drugs 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 241000700157 Rattus norvegicus Species 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000001754 anti-pyretic effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 159000000007 calcium salts Chemical class 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 230000003501 anti-edematous effect Effects 0.000 description 3
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 3
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
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- 239000000443 aerosol Substances 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
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- 229910052791 calcium Inorganic materials 0.000 description 2
- HXEBPMBXOAKYGJ-UHFFFAOYSA-L calcium;2-(3-methyl-2-phenylimino-1,3-thiazol-4-yl)propanoate Chemical compound [Ca+2].CN1C(C(C([O-])=O)C)=CSC1=NC1=CC=CC=C1.CN1C(C(C([O-])=O)C)=CSC1=NC1=CC=CC=C1 HXEBPMBXOAKYGJ-UHFFFAOYSA-L 0.000 description 2
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- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
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- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
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- 150000002430 hydrocarbons Chemical class 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 2
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- 239000011736 potassium bicarbonate Substances 0.000 description 2
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- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 2
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- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
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- QTFLUVRZOBQTBW-UHFFFAOYSA-N 1,3-thiazol-3-ium;iodide Chemical compound [I-].C1=CSC=[NH+]1 QTFLUVRZOBQTBW-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FGIWHTCTNZVPQF-UHFFFAOYSA-N 2-(2-phenylimino-3-prop-2-enyl-1,3-thiazol-5-yl)propanoic acid Chemical compound S1C(C(C(O)=O)C)=CN(CC=C)C1=NC1=CC=CC=C1 FGIWHTCTNZVPQF-UHFFFAOYSA-N 0.000 description 1
- HRSNKNPBIYJDNS-UHFFFAOYSA-N 2-(2-phenylimino-3-propyl-1,3-thiazol-5-yl)propanoic acid Chemical compound CCCN1C=C(C(C)C(O)=O)SC1=NC1=CC=CC=C1 HRSNKNPBIYJDNS-UHFFFAOYSA-N 0.000 description 1
- ZYXSFDALQHXLMA-UHFFFAOYSA-N 2-(3,4-dimethyl-2-phenylimino-1,3-thiazol-5-yl)acetic acid Chemical compound CN1C(C)=C(CC(O)=O)SC1=NC1=CC=CC=C1 ZYXSFDALQHXLMA-UHFFFAOYSA-N 0.000 description 1
- IAVFVWMTQMRBDI-UHFFFAOYSA-N 2-(3,4-dimethyl-2-phenylimino-1,3-thiazol-5-yl)propanoic acid Chemical compound CN1C(C)=C(C(C(O)=O)C)SC1=NC1=CC=CC=C1 IAVFVWMTQMRBDI-UHFFFAOYSA-N 0.000 description 1
- CPUSHUCHXNKKGZ-UHFFFAOYSA-N 2-(3-ethyl-2-phenylimino-1,3-thiazol-4-yl)propanoic acid Chemical compound CCN1C(C(C)C(O)=O)=CSC1=NC1=CC=CC=C1 CPUSHUCHXNKKGZ-UHFFFAOYSA-N 0.000 description 1
- ZASNAVBCBGWWEI-UHFFFAOYSA-N 2-(3-methyl-2-phenylimino-1,3-thiazol-4-yl)acetic acid Chemical compound CN1C(CC(O)=O)=CSC1=NC1=CC=CC=C1 ZASNAVBCBGWWEI-UHFFFAOYSA-N 0.000 description 1
- KTTIMYFUBPWMQM-UHFFFAOYSA-N 2-(3-methyl-2-phenylimino-1,3-thiazol-5-yl)butanoic acid Chemical compound S1C(C(C(O)=O)CC)=CN(C)C1=NC1=CC=CC=C1 KTTIMYFUBPWMQM-UHFFFAOYSA-N 0.000 description 1
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- QYVFGTUCFUERNS-UHFFFAOYSA-N ethyl 2-[3-chloro-4-(1,3-thiazol-2-ylamino)phenyl]propanoate Chemical compound ClC1=CC(C(C)C(=O)OCC)=CC=C1NC1=NC=CS1 QYVFGTUCFUERNS-UHFFFAOYSA-N 0.000 description 1
- JOWSSGXJRKRTBL-UHFFFAOYSA-N ethyl 2-[4-(1,3-thiazol-2-ylamino)phenyl]propanoate Chemical compound C1=CC(C(C)C(=O)OCC)=CC=C1NC1=NC=CS1 JOWSSGXJRKRTBL-UHFFFAOYSA-N 0.000 description 1
- SLTIYMCJZIEECA-UHFFFAOYSA-N ethyl 2-[4-[(3-methyl-1,3-thiazol-2-ylidene)amino]phenyl]propanoate Chemical group C1=CC(C(C)C(=O)OCC)=CC=C1N=C1N(C)C=CS1 SLTIYMCJZIEECA-UHFFFAOYSA-N 0.000 description 1
- 229940093476 ethylene glycol Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- ATADHKWKHYVBTJ-UHFFFAOYSA-N hydron;4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol;chloride Chemical compound Cl.CNCC(O)C1=CC=C(O)C(O)=C1 ATADHKWKHYVBTJ-UHFFFAOYSA-N 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- LMAZKPOSWVOFGY-FBAUPLQOSA-N orine Natural products CO[C@H]1C[C@H](O[C@H]2CC[C@]3(C)[C@H]4C[C@@H](OC(=O)C=Cc5ccccc5)[C@]6(C)[C@@](O)(CC[C@]6(O)[C@]4(O)CC=C3C2)[C@H](C)OC(=O)C=Cc7ccccc7)O[C@H](C)[C@H]1O LMAZKPOSWVOFGY-FBAUPLQOSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000037040 pain threshold Effects 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 150000007979 thiazole derivatives Chemical class 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D277/32—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 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
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49140776A JPS5175065A (enrdf_load_stackoverflow) | 1974-12-06 | 1974-12-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1060024A true CA1060024A (en) | 1979-08-07 |
Family
ID=15276473
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA240,770A Expired CA1060024A (en) | 1974-12-06 | 1975-11-27 | Thiazoline derivatives and production thereof |
Country Status (10)
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6339868A (ja) * | 1986-08-04 | 1988-02-20 | Otsuka Pharmaceut Factory Inc | ジ低級アルキルフエノ−ル誘導体 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1262292A (en) * | 1968-04-09 | 1972-02-02 | Wyeth John & Brother Ltd | Novel thiazoline derivatives, the preparation thereof and compositions containing the same |
-
1974
- 1974-12-06 JP JP49140776A patent/JPS5175065A/ja active Pending
-
1975
- 1975-11-27 CA CA240,770A patent/CA1060024A/en not_active Expired
- 1975-11-28 GB GB4909475A patent/GB1476594A/en not_active Expired
- 1975-12-02 SE SE7513574A patent/SE430064B/xx not_active IP Right Cessation
- 1975-12-04 AU AU87275/75A patent/AU502387B2/en not_active Expired
- 1975-12-05 CH CH1587975A patent/CH621783A5/de not_active IP Right Cessation
- 1975-12-05 DE DE2554863A patent/DE2554863C2/de not_active Expired
- 1975-12-05 DK DK551275A patent/DK144473C/da not_active IP Right Cessation
- 1975-12-05 FR FR7537369A patent/FR2293200A1/fr active Granted
- 1975-12-08 NL NL7514284A patent/NL7514284A/xx not_active Application Discontinuation
-
1980
- 1980-09-09 CH CH677280A patent/CH624109A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NL7514284A (nl) | 1976-06-09 |
| SE430064B (sv) | 1983-10-17 |
| GB1476594A (en) | 1977-06-16 |
| DK551275A (da) | 1976-06-07 |
| CH621783A5 (en) | 1981-02-27 |
| FR2293200B1 (enrdf_load_stackoverflow) | 1978-07-28 |
| DK144473B (da) | 1982-03-15 |
| AU502387B2 (en) | 1979-07-26 |
| DK144473C (da) | 1982-08-30 |
| SE7513574L (sv) | 1976-06-08 |
| DE2554863A1 (de) | 1976-06-16 |
| DE2554863C2 (de) | 1984-08-23 |
| CH624109A5 (en) | 1981-07-15 |
| FR2293200A1 (fr) | 1976-07-02 |
| JPS5175065A (enrdf_load_stackoverflow) | 1976-06-29 |
| AU8727575A (en) | 1977-06-09 |
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