CZ294630B6 - Substituované pyrazolylbenzensulfonamidy pro léčení zánětů - Google Patents

Info

Publication number

CZ294630B6

CZ294630B6 CZ19961503A CZ150396A CZ294630B6 CZ 294630 B6 CZ294630 B6 CZ 294630B6 CZ 19961503 A CZ19961503 A CZ 19961503A CZ 150396 A CZ150396 A CZ 150396A CZ 294630 B6 CZ294630 B6 CZ 294630B6

Authority

CZ

Czechia

Prior art keywords

pyrazol

benzenesulfonamide

trifluoromethyl

phenyl

chlorophenyl

Prior art date

1993-11-30

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• 230000004054 inflammatory process Effects 0.000 title abstract description 14
• 206010061218 Inflammation Diseases 0.000 title abstract description 11
• 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 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 70
• NKYLSWYWAZBKIO-UHFFFAOYSA-N 2-pyrazol-1-ylbenzenesulfonamide Chemical class NS(=O)(=O)C1=CC=CC=C1N1N=CC=C1 NKYLSWYWAZBKIO-UHFFFAOYSA-N 0.000 claims abstract 11
• -1 cyano, carboxyl Chemical group 0.000 claims description 277
• 239000000460 chlorine Substances 0.000 claims description 81
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 34
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 26
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 15
• 125000003118 aryl group Chemical group 0.000 claims description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 13
• 125000003368 amide group Chemical group 0.000 claims description 13
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 claims description 11
• 125000001246 bromo group Chemical group Br* 0.000 claims description 10
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 9
• 229910052801 chlorine Inorganic materials 0.000 claims description 8
• 125000006003 dichloroethyl group Chemical group 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
• 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 7
• 125000006001 difluoroethyl group Chemical group 0.000 claims description 7
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 7
• 125000006343 heptafluoro propyl group Chemical group 0.000 claims description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 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 6
• 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 claims description 6
• 239000011737 fluorine Substances 0.000 claims description 6
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• LSTPZPSAJKPXBD-UHFFFAOYSA-N 4-[5-(cyclohexen-1-yl)-3-(difluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2CCCCC=2)=CC(C(F)F)=N1 LSTPZPSAJKPXBD-UHFFFAOYSA-N 0.000 claims description 5
• NGZXKTYEKJYBIQ-UHFFFAOYSA-N 4-[5-cyclohexyl-3-(difluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C2CCCCC2)=CC(C(F)F)=N1 NGZXKTYEKJYBIQ-UHFFFAOYSA-N 0.000 claims description 5
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 235000010290 biphenyl Nutrition 0.000 claims description 5
• 239000004305 biphenyl Substances 0.000 claims description 5
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000001188 haloalkyl group Chemical group 0.000 claims description 5
• 125000001072 heteroaryl group Chemical group 0.000 claims description 5
• 125000002757 morpholinyl group Chemical group 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• 125000001424 substituent group Chemical group 0.000 claims description 5
• OYZKFVIVPRQRQQ-UHFFFAOYSA-N 1-phenylsulfonamide-3-trifluoromethyl-5-parabromophenylpyrazole Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC(Br)=CC=2)=CC(C(F)(F)F)=N1 OYZKFVIVPRQRQQ-UHFFFAOYSA-N 0.000 claims description 4
• QGNNQDAQBISHQG-UHFFFAOYSA-N 4-[5-(2-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound CC1=CC=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 QGNNQDAQBISHQG-UHFFFAOYSA-N 0.000 claims description 4
• 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 claims description 4
• YLMZYVZMVKJGOT-UHFFFAOYSA-N 4-[5-(4-nitrophenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC(=CC=2)[N+]([O-])=O)=CC(C(F)(F)F)=N1 YLMZYVZMVKJGOT-UHFFFAOYSA-N 0.000 claims description 4
• MQPLMBSDWYIIID-UHFFFAOYSA-N 4-[5-phenyl-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC=CC=2)=CC(C(F)(F)F)=N1 MQPLMBSDWYIIID-UHFFFAOYSA-N 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
• ICRSYPPLGADZKA-UHFFFAOYSA-N hydroxycelecoxib Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC(CO)=CC=2)=CC(C(F)(F)F)=N1 ICRSYPPLGADZKA-UHFFFAOYSA-N 0.000 claims description 4
• TTZNQDOUNXBMJV-UHFFFAOYSA-N mavacoxib Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC(F)=CC=2)=CC(C(F)(F)F)=N1 TTZNQDOUNXBMJV-UHFFFAOYSA-N 0.000 claims description 4
• 239000011593 sulfur Substances 0.000 claims description 4
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 3
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 125000004043 oxo group Chemical group O=* 0.000 claims description 3
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
• LEMZOAJNWONTGE-UHFFFAOYSA-N 4-[3-(difluoromethyl)-5-(4-methylsulfanylphenyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(SC)=CC=C1C1=CC(C(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 LEMZOAJNWONTGE-UHFFFAOYSA-N 0.000 claims description 2
• VKCVJTXXANYFGD-UHFFFAOYSA-N 4-[5-(2,4-dichlorophenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C(=CC(Cl)=CC=2)Cl)=CC(C(F)(F)F)=N1 VKCVJTXXANYFGD-UHFFFAOYSA-N 0.000 claims description 2
• MPVPOTMPKLOUHZ-UHFFFAOYSA-N 4-[5-(3-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound CC1=CC=CC(C=2N(N=C(C=2)C(F)(F)F)C=2C=CC(=CC=2)S(N)(=O)=O)=C1 MPVPOTMPKLOUHZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
• JNYLMODTPLSLIF-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carboxylic acid Chemical group OC(=O)C1=CC=C(C(F)(F)F)N=C1 JNYLMODTPLSLIF-UHFFFAOYSA-N 0.000 claims description 2
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 2
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 2
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 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 description 2
• NGFQXYLWQODUIL-UHFFFAOYSA-N cyclohexylazanide Chemical compound [NH-]C1CCCCC1 NGFQXYLWQODUIL-UHFFFAOYSA-N 0.000 claims 4
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 2
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 1
• 125000004429 atom Chemical group 0.000 claims 1
• 125000004093 cyano group Chemical group *C#N 0.000 claims 1
• 125000001153 fluoro group Chemical group F* 0.000 claims 1
• 150000002431 hydrogen Chemical class 0.000 claims 1
• 125000001148 pentyloxycarbonyl group Chemical group 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
• 239000002260 anti-inflammatory agent Substances 0.000 abstract description 5
• 208000035475 disorder Diseases 0.000 abstract description 4
• 206010003246 arthritis Diseases 0.000 abstract description 3
• 230000001741 anti-phlogistic effect Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 217
• 239000000243 solution Substances 0.000 description 127
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 111
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 100
• 238000002360 preparation method Methods 0.000 description 96
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 92
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 90
• 239000011541 reaction mixture Substances 0.000 description 72
• 239000000203 mixture Substances 0.000 description 71
• 239000007787 solid Substances 0.000 description 71
• 150000003254 radicals Chemical class 0.000 description 68
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
• 238000005481 NMR spectroscopy Methods 0.000 description 59
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 46
• 235000019341 magnesium sulphate Nutrition 0.000 description 46
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 44
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
• 238000000034 method Methods 0.000 description 38
• 235000019441 ethanol Nutrition 0.000 description 37
• 125000004432 carbon atom Chemical group C* 0.000 description 35
• 238000010992 reflux Methods 0.000 description 35
• 239000012267 brine Substances 0.000 description 34
• 239000000047 product Substances 0.000 description 34
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
• 238000004458 analytical method Methods 0.000 description 33
• 238000002844 melting Methods 0.000 description 33
• 230000008018 melting Effects 0.000 description 33
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
• 150000003217 pyrazoles Chemical class 0.000 description 26
• 239000000725 suspension Substances 0.000 description 25
• 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 23
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• 150000002576 ketones Chemical class 0.000 description 22
• 239000003921 oil Substances 0.000 description 22
• 235000019198 oils Nutrition 0.000 description 22
• 239000012044 organic layer Substances 0.000 description 22
• 125000005594 diketone group Chemical group 0.000 description 21
• KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 20
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 19
• 239000000741 silica gel Substances 0.000 description 19
• 229910002027 silica gel Inorganic materials 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 235000002639 sodium chloride Nutrition 0.000 description 17
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 15
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 15
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 15
• 150000005840 aryl radicals Chemical class 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 14
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
• NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 12
• JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• 239000010410 layer Substances 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• 125000003277 amino group Chemical group 0.000 description 10
• 150000002148 esters Chemical class 0.000 description 10
• 230000005764 inhibitory process Effects 0.000 description 10
• 125000004433 nitrogen atom Chemical group N* 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• 239000007858 starting material Substances 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• 229960000583 acetic acid Drugs 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 238000003818 flash chromatography Methods 0.000 description 9
• 238000001819 mass spectrum Methods 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• 241000700159 Rattus Species 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 8
• 241000701447 unidentified baculovirus Species 0.000 description 8
• BUZYGTVTZYSBCU-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1 BUZYGTVTZYSBCU-UHFFFAOYSA-N 0.000 description 7
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 7
• 150000001299 aldehydes Chemical class 0.000 description 7
• 230000037396 body weight Effects 0.000 description 7
• 239000000679 carrageenan Substances 0.000 description 7
• 235000010418 carrageenan Nutrition 0.000 description 7
• 229920001525 carrageenan Polymers 0.000 description 7
• 229940113118 carrageenan Drugs 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 238000003760 magnetic stirring Methods 0.000 description 7
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 7
• 125000004430 oxygen atom Chemical group O* 0.000 description 7
• 150000003180 prostaglandins Chemical class 0.000 description 7
• 125000004434 sulfur atom Chemical group 0.000 description 7
• 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 7
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