JPS6254105B2 - - Google Patents

Info

Publication number

JPS6254105B2

JPS6254105B2 JP54062779A JP6277979A JPS6254105B2 JP S6254105 B2 JPS6254105 B2 JP S6254105B2 JP 54062779 A JP54062779 A JP 54062779A JP 6277979 A JP6277979 A JP 6277979A JP S6254105 B2 JPS6254105 B2 JP S6254105B2

Authority

JP

Japan

Prior art keywords

group

acid

hydrogen atom

atom

carbon atoms

Prior art date

1978-05-24

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

• Espacenet
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 68
• 150000001875 compounds Chemical class 0.000 claims description 57
• 239000002253 acid Chemical class 0.000 claims description 56
• 229910052801 chlorine Inorganic materials 0.000 claims description 55
• -1 2-hydroxyethoxy Chemical group 0.000 claims description 54
• 150000003839 salts Chemical class 0.000 claims description 54
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 52
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
• 125000004432 carbon atom Chemical group C* 0.000 claims description 33
• 238000006243 chemical reaction Methods 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 28
• 238000000034 method Methods 0.000 claims description 19
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
• RFBFZTAOPICSHT-UHFFFAOYSA-N acetic acid;n-phenylthiophen-2-amine Chemical class CC(O)=O.C=1C=CC=CC=1NC1=CC=CS1 RFBFZTAOPICSHT-UHFFFAOYSA-N 0.000 claims description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
• AELILMBZWCGOSB-UHFFFAOYSA-N 2-[4-(2,6-dichloroanilino)thiophen-3-yl]acetic acid Chemical compound OC(=O)CC1=CSC=C1NC1=C(Cl)C=CC=C1Cl AELILMBZWCGOSB-UHFFFAOYSA-N 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 12
• 150000002148 esters Chemical class 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• ACBYDMGMWUOHHV-UHFFFAOYSA-N 2-(3-anilinothiophen-2-yl)acetic acid Chemical class S1C=CC(NC=2C=CC=CC=2)=C1CC(=O)O ACBYDMGMWUOHHV-UHFFFAOYSA-N 0.000 claims description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
• 150000007513 acids Chemical class 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
• 238000003797 solvolysis reaction Methods 0.000 claims description 10
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
• 125000002843 carboxylic acid group Chemical group 0.000 claims description 6
• 239000002904 solvent Substances 0.000 claims description 6
• 125000004423 acyloxy group Chemical group 0.000 claims description 5
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 5
• 230000008569 process Effects 0.000 claims description 5
• 238000000354 decomposition reaction Methods 0.000 claims description 3
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 3
• 235000011054 acetic acid Nutrition 0.000 claims description 2
• 230000000144 pharmacologic effect Effects 0.000 claims description 2
• TXFQJRFOGGSJCI-UHFFFAOYSA-N 2-(3-aminothiophen-2-yl)acetic acid Chemical class NC=1C=CSC=1CC(O)=O TXFQJRFOGGSJCI-UHFFFAOYSA-N 0.000 claims 1
• 125000004429 atom Chemical group 0.000 claims 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• 238000002360 preparation method Methods 0.000 claims 1
• 230000008018 melting Effects 0.000 description 53
• 238000002844 melting Methods 0.000 description 53
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
• 239000000243 solution Substances 0.000 description 38
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 32
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
• 241001465754 Metazoa Species 0.000 description 22
• MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 20
• 239000003814 drug Substances 0.000 description 19
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• 229940079593 drug Drugs 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 15
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• 239000000203 mixture Substances 0.000 description 12
• 241000699670 Mus sp. Species 0.000 description 11
• 239000013543 active substance Substances 0.000 description 11
• 239000000284 extract Substances 0.000 description 11
• 230000003110 anti-inflammatory effect Effects 0.000 description 10
• 239000002244 precipitate Substances 0.000 description 10
• 235000011121 sodium hydroxide Nutrition 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 238000009835 boiling Methods 0.000 description 9
• 239000012074 organic phase Substances 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
• 230000001754 anti-pyretic effect Effects 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
• 235000008504 concentrate Nutrition 0.000 description 7
• 239000012141 concentrate Substances 0.000 description 7
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• CPSPZBZRRLXMSY-UHFFFAOYSA-N 2-[4-(2,6-dichloroanilino)thiophen-3-yl]acetonitrile Chemical compound ClC1=CC=CC(Cl)=C1NC1=CSC=C1CC#N CPSPZBZRRLXMSY-UHFFFAOYSA-N 0.000 description 6
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
• 206010061218 Inflammation Diseases 0.000 description 6
• 208000002193 Pain Diseases 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 6
• 235000012239 silicon dioxide Nutrition 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• 241000124008 Mammalia Species 0.000 description 5
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
• DOWGQSKPFQDYIZ-UHFFFAOYSA-N [BH2-].[Na+] Chemical compound [BH2-].[Na+] DOWGQSKPFQDYIZ-UHFFFAOYSA-N 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 150000002168 ethanoic acid esters Chemical class 0.000 description 5
• 235000019439 ethyl acetate Nutrition 0.000 description 5
• 239000000796 flavoring agent Substances 0.000 description 5
• 238000005755 formation reaction Methods 0.000 description 5
• 239000008187 granular material Substances 0.000 description 5
• 230000004054 inflammatory process Effects 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• 150000002825 nitriles Chemical class 0.000 description 5
• 239000000825 pharmaceutical preparation Substances 0.000 description 5
• 238000007127 saponification reaction Methods 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• 239000003765 sweetening agent Substances 0.000 description 5
• 230000008961 swelling Effects 0.000 description 5
• 238000010626 work up procedure Methods 0.000 description 5
• CAFPCOFXOKWMQF-UHFFFAOYSA-N 2-[3-(2,6-dichloroanilino)thiophen-2-yl]acetic acid Chemical compound S1C=CC(NC=2C(=CC=CC=2Cl)Cl)=C1CC(=O)O CAFPCOFXOKWMQF-UHFFFAOYSA-N 0.000 description 4
• NJPJNXIMOMOYSG-UHFFFAOYSA-N 3-anilinothiophene-2-carboxylic acid Chemical compound S1C=CC(NC=2C=CC=CC=2)=C1C(=O)O NJPJNXIMOMOYSG-UHFFFAOYSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 229920000742 Cotton Polymers 0.000 description 4
• 206010030113 Oedema Diseases 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• 239000005662 Paraffin oil Substances 0.000 description 4
• 206010037660 Pyrexia Diseases 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 238000006136 alcoholysis reaction Methods 0.000 description 4
• 230000000202 analgesic effect Effects 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 235000010418 carrageenan Nutrition 0.000 description 4
• 229920001525 carrageenan Polymers 0.000 description 4
• 235000013355 food flavoring agent Nutrition 0.000 description 4
• 235000003599 food sweetener Nutrition 0.000 description 4
• 230000002140 halogenating effect Effects 0.000 description 4
• 230000026030 halogenation Effects 0.000 description 4
• 238000005658 halogenation reaction Methods 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• 239000012442 inert solvent Substances 0.000 description 4
• 239000012280 lithium aluminium hydride Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• VCESDBDLBWABPV-UHFFFAOYSA-N methyl 2-[4-(2,6-dichloroanilino)thiophen-3-yl]acetate Chemical compound COC(=O)CC1=CSC=C1NC1=C(Cl)C=CC=C1Cl VCESDBDLBWABPV-UHFFFAOYSA-N 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 238000001953 recrystallisation Methods 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 description 3
• XEHWUIYOKWYSSZ-UHFFFAOYSA-N 2-[4-(2,6-dimethylanilino)thiophen-3-yl]acetic acid Chemical compound CC1=CC=CC(C)=C1NC1=CSC=C1CC(O)=O XEHWUIYOKWYSSZ-UHFFFAOYSA-N 0.000 description 3
• SFAPTSMWCKIVON-UHFFFAOYSA-N 2-[4-(2-chloro-3-methylanilino)thiophen-3-yl]acetic acid Chemical compound CC1=CC=CC(NC=2C(=CSC=2)CC(O)=O)=C1Cl SFAPTSMWCKIVON-UHFFFAOYSA-N 0.000 description 3
• XXVYZRFDURSXOE-UHFFFAOYSA-N 2-[4-(2-chloro-6-methylanilino)thiophen-3-yl]acetic acid Chemical compound CC1=CC=CC(Cl)=C1NC1=CSC=C1CC(O)=O XXVYZRFDURSXOE-UHFFFAOYSA-N 0.000 description 3
• WOAWQZULIHPWDB-UHFFFAOYSA-N 2-[5-chloro-4-(2-chloro-6-methylanilino)thiophen-3-yl]acetic acid Chemical compound CC1=CC=CC(Cl)=C1NC1=C(Cl)SC=C1CC(O)=O WOAWQZULIHPWDB-UHFFFAOYSA-N 0.000 description 3
• LWRDXDNBYFQTCT-UHFFFAOYSA-N 4-(2-chloro-6-methylanilino)thiophene-3-carboxylic acid Chemical compound CC1=CC=CC(Cl)=C1NC1=CSC=C1C(O)=O LWRDXDNBYFQTCT-UHFFFAOYSA-N 0.000 description 3
• PPYVATYRURMAAX-UHFFFAOYSA-N 4-(chloromethyl)-n-(2-chloro-3-methylphenyl)thiophen-3-amine Chemical compound CC1=CC=CC(NC=2C(=CSC=2)CCl)=C1Cl PPYVATYRURMAAX-UHFFFAOYSA-N 0.000 description 3
• UWKBHCAWRQRRGJ-UHFFFAOYSA-N 4-anilinothiophene-3-carboxylic acid Chemical compound OC(=O)C1=CSC=C1NC1=CC=CC=C1 UWKBHCAWRQRRGJ-UHFFFAOYSA-N 0.000 description 3
• 244000215068 Acacia senegal Species 0.000 description 3
• 235000006491 Acacia senegal Nutrition 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 240000001624 Espostoa lanata Species 0.000 description 3
• 235000009161 Espostoa lanata Nutrition 0.000 description 3
• 208000009386 Experimental Arthritis Diseases 0.000 description 3
• 229920000084 Gum arabic Polymers 0.000 description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
• 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 3
• 241000699666 Mus <mouse, genus> Species 0.000 description 3
• 235000019483 Peanut oil Nutrition 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
• FOVFDFPBSQMFOO-UHFFFAOYSA-N [4-(2,6-dichloroanilino)thiophen-3-yl]methanol Chemical compound OCC1=CSC=C1NC1=C(Cl)C=CC=C1Cl FOVFDFPBSQMFOO-UHFFFAOYSA-N 0.000 description 3
• 235000010489 acacia gum Nutrition 0.000 description 3
• 229960000583 acetic acid Drugs 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 239000002221 antipyretic Substances 0.000 description 3
• 239000007900 aqueous suspension Substances 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 238000004061 bleaching Methods 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• 230000002354 daily effect Effects 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 201000010099 disease Diseases 0.000 description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 238000004821 distillation Methods 0.000 description 3
• 239000012153 distilled water Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• QLSRSLGIQJGALU-UHFFFAOYSA-N ethyl 2-[3-(2,6-dichloroanilino)thiophen-2-yl]-2-oxoacetate Chemical compound S1C=CC(NC=2C(=CC=CC=2Cl)Cl)=C1C(=O)C(=O)OCC QLSRSLGIQJGALU-UHFFFAOYSA-N 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• 229910052739 hydrogen Inorganic materials 0.000 description 3
• 238000007327 hydrogenolysis reaction Methods 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• PPECUTDHISTLTF-UHFFFAOYSA-N methyl 2-[5-chloro-4-(2-chloro-6-methylanilino)thiophen-3-yl]acetate Chemical compound COC(=O)CC1=CSC(Cl)=C1NC1=C(C)C=CC=C1Cl PPECUTDHISTLTF-UHFFFAOYSA-N 0.000 description 3
• TUSSXVYKOOVOID-UHFFFAOYSA-N methyl 3-oxothiolane-2-carboxylate Chemical compound COC(=O)C1SCCC1=O TUSSXVYKOOVOID-UHFFFAOYSA-N 0.000 description 3
• 125000002560 nitrile group Chemical group 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 235000008390 olive oil Nutrition 0.000 description 3
• 239000000312 peanut oil Substances 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• 239000011591 potassium Substances 0.000 description 3
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 239000002994 raw material Substances 0.000 description 3
• 230000035484 reaction time Effects 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 3
• 159000000000 sodium salts Chemical class 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 238000012453 sprague-dawley rat model Methods 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 239000008399 tap water Substances 0.000 description 3
• 235000020679 tap water Nutrition 0.000 description 3
• 231100001274 therapeutic index Toxicity 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
• YUZICJITAGPRGZ-UHFFFAOYSA-N 1-(2,6-dichlorophenyl)-3h-thieno[3,4-b]pyrrol-2-one Chemical compound ClC1=CC=CC(Cl)=C1N1C2=CSC=C2CC1=O YUZICJITAGPRGZ-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• GHNAUCQJEAXYSE-UHFFFAOYSA-N 2-[3-(2,6-dichloroanilino)-4-methylthiophen-2-yl]-2-oxoacetic acid Chemical compound CC1=CSC(C(=O)C(O)=O)=C1NC1=C(Cl)C=CC=C1Cl GHNAUCQJEAXYSE-UHFFFAOYSA-N 0.000 description 2
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