NO321157B1 - Anvendelse av substituerte pyrazolylbenzensulfonamider for fremstilling av et antiinflammatorisk middel til bruk innen veterinaermedisin. - Google Patents

Info

Publication number

NO321157B1

NO321157B1 NO19981392A NO981392A NO321157B1 NO 321157 B1 NO321157 B1 NO 321157B1 NO 19981392 A NO19981392 A NO 19981392A NO 981392 A NO981392 A NO 981392A NO 321157 B1 NO321157 B1 NO 321157B1

Authority

NO

Norway

Prior art keywords

pyrazol

mmol

phenyl

benzenesulfonamide

trifluoromethyl

Prior art date

1995-09-29

Links

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• Global Dossier
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• 239000003814 drug Substances 0.000 title claims description 10
• 238000002360 preparation method Methods 0.000 title description 61
• HMDUADNDMXESSJ-UHFFFAOYSA-N 2-(1h-pyrazol-5-yl)benzenesulfonamide Chemical class NS(=O)(=O)C1=CC=CC=C1C1=CC=NN1 HMDUADNDMXESSJ-UHFFFAOYSA-N 0.000 title description 5
• 239000002260 anti-inflammatory agent Substances 0.000 title description 5
• 229940121363 anti-inflammatory agent Drugs 0.000 title description 4
• 230000004054 inflammatory process Effects 0.000 claims abstract description 23
• 206010061218 Inflammation Diseases 0.000 claims abstract description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
• 208000035475 disorder Diseases 0.000 claims abstract description 4
• -1 cyano, carboxyl Chemical group 0.000 claims description 85
• 150000001875 compounds Chemical class 0.000 claims description 65
• 150000003254 radicals Chemical class 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 17
• 239000000460 chlorine Substances 0.000 claims description 16
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 241000282472 Canis lupus familiaris Species 0.000 claims description 6
• 208000002193 Pain Diseases 0.000 claims description 6
• 230000037396 body weight Effects 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 230000036407 pain Effects 0.000 claims description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 229910052736 halogen Inorganic materials 0.000 claims description 5
• 150000002367 halogens Chemical class 0.000 claims description 5
• 125000001145 hydrido group Chemical group *[H] 0.000 claims description 5
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• 229910052794 bromium Inorganic materials 0.000 claims description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 229910052731 fluorine Inorganic materials 0.000 claims description 4
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 3
• 125000006003 dichloroethyl group Chemical group 0.000 claims description 3
• 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 claims description 3
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 claims description 3
• 125000006001 difluoroethyl group Chemical group 0.000 claims description 3
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 3
• 239000011737 fluorine Substances 0.000 claims description 3
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 3
• 125000006343 heptafluoro propyl group Chemical group 0.000 claims description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
• 201000008482 osteoarthritis Diseases 0.000 claims description 3
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 2
• MPHUNBLFEKLVLF-UHFFFAOYSA-N 4-[3-(difluoromethyl)-5-(4-methylphenyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 MPHUNBLFEKLVLF-UHFFFAOYSA-N 0.000 claims description 2
• ZFFYQVIHYPYXPI-UHFFFAOYSA-N 4-[3-(difluoromethyl)-5-phenylpyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC=CC=2)=CC(C(F)F)=N1 ZFFYQVIHYPYXPI-UHFFFAOYSA-N 0.000 claims description 2
• XRHRZRHLXNWUTF-UHFFFAOYSA-N 4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=C(Cl)C(C(F)(F)F)=N1 XRHRZRHLXNWUTF-UHFFFAOYSA-N 0.000 claims description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
• 125000003545 alkoxy group Chemical group 0.000 claims description 2
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
• 125000004744 butyloxycarbonyl group Chemical group 0.000 claims 2
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 2
• 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 claims 2
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 2
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 2
• 125000001148 pentyloxycarbonyl group Chemical group 0.000 claims 2
• 125000004742 propyloxycarbonyl group Chemical group 0.000 claims 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
• AJYWXMJXJSEWLW-UHFFFAOYSA-N 4-(4-chloro-5-phenylpyrazol-1-yl)benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC=CC=2)=C(Cl)C=N1 AJYWXMJXJSEWLW-UHFFFAOYSA-N 0.000 claims 1
• UTAMLNUWNIAVPF-UHFFFAOYSA-N 4-[3-(difluoromethyl)-5-(2-fluoro-4-methoxyphenyl)pyrazol-1-yl]benzenesulfonamide Chemical compound FC1=CC(OC)=CC=C1C1=CC(C(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 UTAMLNUWNIAVPF-UHFFFAOYSA-N 0.000 claims 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims 1
• 229940077388 benzenesulfonate Drugs 0.000 claims 1
• 125000004663 dialkyl amino group Chemical group 0.000 claims 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 24
• 241001465754 Metazoa Species 0.000 abstract description 5
• IGCQXMQOKRXHHN-UHFFFAOYSA-N n-(1h-pyrazol-5-yl)benzenesulfonamide Chemical class C=1C=CC=CC=1S(=O)(=O)NC=1C=CNN=1 IGCQXMQOKRXHHN-UHFFFAOYSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 147
• 239000000243 solution Substances 0.000 description 89
• 239000000203 mixture Substances 0.000 description 76
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 72
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 65
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
• 235000019439 ethyl acetate Nutrition 0.000 description 52
• 239000007787 solid Substances 0.000 description 50
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
• 239000011541 reaction mixture Substances 0.000 description 37
• 238000010992 reflux Methods 0.000 description 30
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
• 238000005481 NMR spectroscopy Methods 0.000 description 28
• 238000004458 analytical method Methods 0.000 description 27
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 26
• 239000000047 product Substances 0.000 description 26
• 239000012267 brine Substances 0.000 description 24
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
• 235000019341 magnesium sulphate Nutrition 0.000 description 23
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
• 238000006243 chemical reaction Methods 0.000 description 21
• 235000019441 ethanol Nutrition 0.000 description 21
• 239000003921 oil Substances 0.000 description 21
• 235000019198 oils Nutrition 0.000 description 21
• 235000002639 sodium chloride Nutrition 0.000 description 17
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• 239000012044 organic layer Substances 0.000 description 15
• IKEURONJLPUALY-UHFFFAOYSA-N 4-hydrazinylbenzenesulfonamide;hydron;chloride Chemical compound [Cl-].NS(=O)(=O)C1=CC=C(N[NH3+])C=C1 IKEURONJLPUALY-UHFFFAOYSA-N 0.000 description 14
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 13
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 238000009472 formulation Methods 0.000 description 12
• 239000004480 active ingredient Substances 0.000 description 11
• 239000010410 layer Substances 0.000 description 11
• KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 10
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 239000000463 material Substances 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• 125000005594 diketone group Chemical group 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 9
• 241000701447 unidentified baculovirus Species 0.000 description 9
• NSQNZEUFHPTJME-UHFFFAOYSA-N 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(C(F)(F)F)=N1 NSQNZEUFHPTJME-UHFFFAOYSA-N 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 235000010418 carrageenan Nutrition 0.000 description 8
• 239000000679 carrageenan Substances 0.000 description 8
• 229920001525 carrageenan Polymers 0.000 description 8
• 229940113118 carrageenan Drugs 0.000 description 8
• 238000003818 flash chromatography Methods 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• 150000003180 prostaglandins Chemical class 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
• NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 7
• 241000700159 Rattus Species 0.000 description 7
• JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 7
• 239000012071 phase Substances 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• BUZYGTVTZYSBCU-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1 BUZYGTVTZYSBCU-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
• YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000003995 emulsifying agent Substances 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 239000006071 cream Substances 0.000 description 5
• 239000012043 crude product Substances 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 239000003925 fat Substances 0.000 description 5
• 235000019197 fats Nutrition 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• YYMGYENEYKIXFZ-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-1-(4-sulfamoylphenyl)pyrazole-3-carboxylate Chemical compound C=1C=C(S(N)(=O)=O)C=CC=1N1N=C(C(=O)OC)C=C1C1=CC=C(Cl)C=C1 YYMGYENEYKIXFZ-UHFFFAOYSA-N 0.000 description 5
• 239000008194 pharmaceutical composition Substances 0.000 description 5
• 229920006395 saturated elastomer Polymers 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
• LOMVENUNSWAXEN-UHFFFAOYSA-N Methyl oxalate Chemical compound COC(=O)C(=O)OC LOMVENUNSWAXEN-UHFFFAOYSA-N 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
• 239000012346 acetyl chloride Substances 0.000 description 4
• 239000003472 antidiabetic agent Substances 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• 238000001819 mass spectrum Methods 0.000 description 4
• NTPLXRHDUXRPNE-UHFFFAOYSA-N methyl p-methoxyphenyl ketone Natural products COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 150000003217 pyrazoles Chemical class 0.000 description 4
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• OUJZNFJFMAKGMS-UHFFFAOYSA-N 1-(3,5-difluoro-4-methoxyphenyl)ethanone Chemical compound COC1=C(F)C=C(C(C)=O)C=C1F OUJZNFJFMAKGMS-UHFFFAOYSA-N 0.000 description 3
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