JP2003509378A - ＩＬ−１ｒａとＩＬ−１プロセシング・放出阻害化合物の併用療法 - Google Patents

ＩＬ−１ｒａとＩＬ−１プロセシング・放出阻害化合物の併用療法

Info

Publication number: JP2003509378A
Authority: JP; Japan
Prior art keywords: alkyl; urea; hydroxy; aryl; sulfonyl
Prior art date: 1999-09-14
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.): Pending

Application number

JP2001523022A

Other languages

English (en)

Japanese (ja)

Inventor

リットマン，ブルース・ヘンリー

ウッドワース，タシャ・ルイス・グッドウィン

ドムブロスキ，マーク・アンソニー

Original Assignee

ファイザー・プロダクツ・インク

Priority date (The priority date 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 date listed.)

1999-09-14

Filing date

2000-08-28

Publication date

2003-03-11

2000-08-28 Application filed by ファイザー・プロダクツ・インク filed Critical ファイザー・プロダクツ・インク

2003-03-11 Publication of JP2003509378A publication Critical patent/JP2003509378A/ja

Status Pending legal-status Critical Current

Links

108010002352 Interleukin-1 Proteins 0.000 title claims abstract description 118
239000003112 inhibitor Substances 0.000 title claims abstract description 115
238000012545 processing Methods 0.000 title claims abstract description 90
150000001875 compounds Chemical class 0.000 title claims description 117
108040001669 interleukin-1 receptor antagonist activity proteins Proteins 0.000 title claims description 85
102000009634 interleukin-1 receptor antagonist activity proteins Human genes 0.000 title claims description 85
238000002648 combination therapy Methods 0.000 title description 5
239000000203 mixture Substances 0.000 claims abstract description 126
102000000589 Interleukin-1 Human genes 0.000 claims abstract description 117
108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 108
102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 102
238000000034 method Methods 0.000 claims abstract description 100
229920001184 polypeptide Polymers 0.000 claims abstract description 98
238000011282 treatment Methods 0.000 claims abstract description 32
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
201000010099 disease Diseases 0.000 claims abstract description 22
230000001404 mediated effect Effects 0.000 claims abstract description 16
230000002265 prevention Effects 0.000 claims abstract description 6
-1 perfluoro Chemical group 0.000 claims description 241
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 159
239000001257 hydrogen Substances 0.000 claims description 125
229910052739 hydrogen Inorganic materials 0.000 claims description 125
239000000126 substance Substances 0.000 claims description 102
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 88
239000004202 carbamide Substances 0.000 claims description 84
125000005843 halogen group Chemical group 0.000 claims description 71
125000003118 aryl group Chemical group 0.000 claims description 65
150000003839 salts Chemical class 0.000 claims description 57
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 48
125000000217 alkyl group Chemical group 0.000 claims description 41
125000004093 cyano group Chemical group *C#N 0.000 claims description 33
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 32
239000001301 oxygen Substances 0.000 claims description 32
229910052760 oxygen Inorganic materials 0.000 claims description 32
150000002431 hydrogen Chemical class 0.000 claims description 30
229910052757 nitrogen Inorganic materials 0.000 claims description 30
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 25
125000001072 heteroaryl group Chemical group 0.000 claims description 23
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 22
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 21
125000004442 acylamino group Chemical group 0.000 claims description 21
229910052717 sulfur Inorganic materials 0.000 claims description 21
239000011593 sulfur Substances 0.000 claims description 21
125000005936 piperidyl group Chemical group 0.000 claims description 20
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 19
125000004423 acyloxy group Chemical group 0.000 claims description 16
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 15
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 15
125000005110 aryl thio group Chemical group 0.000 claims description 15
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 11
125000001153 fluoro group Chemical group F* 0.000 claims description 11
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
125000005035 acylthio group Chemical group 0.000 claims description 10
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 10
125000005241 heteroarylamino group Chemical group 0.000 claims description 10
125000005368 heteroarylthio group Chemical group 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
241000124008 Mammalia Species 0.000 claims description 8
125000004104 aryloxy group Chemical group 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 7
HLEOGYNUFBFPQF-UHFFFAOYSA-N 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(2-hydroxypropan-2-yl)thiophen-2-yl]sulfonylurea Chemical compound CC(C)(O)C1=CSC(S(=O)(=O)NC(=O)NC=2C=3CCCC=3C=C3CCCC3=2)=C1 HLEOGYNUFBFPQF-UHFFFAOYSA-N 0.000 claims description 7
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 7
125000004181 carboxyalkyl group Chemical group 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000001544 thienyl group Chemical group 0.000 claims description 6
229910052720 vanadium Inorganic materials 0.000 claims description 6
125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 5
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
241001024304 Mino Species 0.000 claims description 5
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
125000001769 aryl amino group Chemical group 0.000 claims description 5
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
NYGHGTMKALXFIA-UHFFFAOYSA-N azapetine Chemical compound C1N(CC=C)CC2=CC=CC=C2C2=CC=CC=C21 NYGHGTMKALXFIA-UHFFFAOYSA-N 0.000 claims description 5
229960004779 azapetine Drugs 0.000 claims description 5
125000005605 benzo group Chemical group 0.000 claims description 5
125000005145 cycloalkylaminosulfonyl group Chemical group 0.000 claims description 5
125000005553 heteroaryloxy group Chemical group 0.000 claims description 5
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
NQUWYENCXXXALZ-UHFFFAOYSA-N 1-(1,2,3,5,6,7-hexahydrodicyclopenta[2,1-b:2',1'-f]pyridin-8-yl)-3-[4-(2-hydroxypropan-2-yl)furan-2-yl]sulfonylurea Chemical compound CC(C)(O)C1=COC(S(=O)(=O)NC(=O)NC=2C=3CCCC=3N=C3CCCC3=2)=C1 NQUWYENCXXXALZ-UHFFFAOYSA-N 0.000 claims description 4
CGMGDAMGECINTJ-UHFFFAOYSA-N 1-(8-chloro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(2-hydroxypropan-2-yl)furan-2-yl]sulfonylurea Chemical compound CC(C)(O)C1=COC(S(=O)(=O)NC(=O)NC=2C=3CCCC=3C(Cl)=C3CCCC3=2)=C1 CGMGDAMGECINTJ-UHFFFAOYSA-N 0.000 claims description 4
MRKXXRUHPFFURP-UHFFFAOYSA-N 1-[2,6-di(propan-2-yl)phenyl]-3-[4-(2-hydroxypropan-2-yl)furan-2-yl]sulfonylurea Chemical compound CC(C)C1=CC=CC(C(C)C)=C1NC(=O)NS(=O)(=O)C1=CC(C(C)(C)O)=CO1 MRKXXRUHPFFURP-UHFFFAOYSA-N 0.000 claims description 4
XWCBFDOFNSSQDA-UHFFFAOYSA-N 1-[4-chloro-2,6-di(propan-2-yl)phenyl]-3-[2-fluoro-5-(oxiran-2-yl)phenyl]sulfonylurea Chemical compound CC(C)C1=CC(Cl)=CC(C(C)C)=C1NC(=O)NS(=O)(=O)C1=CC(C2OC2)=CC=C1F XWCBFDOFNSSQDA-UHFFFAOYSA-N 0.000 claims description 4
125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
230000003637 steroidlike Effects 0.000 claims description 4
HUUSXLKCTQDPGL-UHFFFAOYSA-N 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(2-hydroxypropan-2-yl)furan-2-yl]sulfonylurea Chemical compound CC(C)(O)C1=COC(S(=O)(=O)NC(=O)NC=2C=3CCCC=3C=C3CCCC3=2)=C1 HUUSXLKCTQDPGL-UHFFFAOYSA-N 0.000 claims description 3
DDRGGWOWUJRBRH-UHFFFAOYSA-N 1-(4-acetylthiophen-2-yl)sulfonyl-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea Chemical compound CC(=O)C1=CSC(S(=O)(=O)NC(=O)NC=2C=3CCCC=3C=C3CCCC3=2)=C1 DDRGGWOWUJRBRH-UHFFFAOYSA-N 0.000 claims description 3
NBWQTLZBXIGFNU-UHFFFAOYSA-N 1-(8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(2-hydroxypropan-2-yl)furan-2-yl]sulfonylurea Chemical compound CC(C)(O)C1=COC(S(=O)(=O)NC(=O)NC=2C=3CCCC=3C(F)=C3CCCC3=2)=C1 NBWQTLZBXIGFNU-UHFFFAOYSA-N 0.000 claims description 3
SUTZSKVFUCJIBG-UHFFFAOYSA-N 1-[(6-fluoro-1h-benzimidazol-5-yl)sulfonyl]-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea Chemical compound FC1=CC=2NC=NC=2C=C1S(=O)(=O)NC(=O)NC1=C2CCCC2=CC2=C1CCC2 SUTZSKVFUCJIBG-UHFFFAOYSA-N 0.000 claims description 3
SKRPFWPDHPSIJV-UHFFFAOYSA-N 1-[2,6-di(propan-2-yl)phenyl]-3-[4-(2-hydroxypropan-2-yl)thiophen-2-yl]sulfonylurea Chemical compound CC(C)C1=CC=CC(C(C)C)=C1NC(=O)NS(=O)(=O)C1=CC(C(C)(C)O)=CS1 SKRPFWPDHPSIJV-UHFFFAOYSA-N 0.000 claims description 3
FOZXAQVPKYKBNY-UHFFFAOYSA-N 1-[4-(1,3-dioxolan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea Chemical compound C=12CCCC2=CC=2CCCC=2C=1NC(=O)NS(=O)(=O)C(OC=1)=CC=1C1OCCO1 FOZXAQVPKYKBNY-UHFFFAOYSA-N 0.000 claims description 3
YUSFXGQGPSLKHV-UHFFFAOYSA-N 1-[4-chloro-2,6-di(propan-2-yl)phenyl]-3-(1h-indol-6-ylsulfonyl)urea Chemical compound CC(C)C1=CC(Cl)=CC(C(C)C)=C1NC(=O)NS(=O)(=O)C1=CC=C(C=CN2)C2=C1 YUSFXGQGPSLKHV-UHFFFAOYSA-N 0.000 claims description 3
NMPXFRKPFCOTDU-UHFFFAOYSA-N 1-[4-chloro-2,6-di(propan-2-yl)phenyl]-3-[(5-fluoro-1h-indol-6-yl)sulfonyl]urea Chemical compound CC(C)C1=CC(Cl)=CC(C(C)C)=C1NC(=O)NS(=O)(=O)C(C(=C1)F)=CC2=C1C=CN2 NMPXFRKPFCOTDU-UHFFFAOYSA-N 0.000 claims description 3
YRSBLSHMKVQWHP-UHFFFAOYSA-N 1-[4-chloro-2,6-di(propan-2-yl)phenyl]-3-[3-(2-hydroxypropan-2-yl)phenyl]sulfonylurea Chemical compound CC(C)C1=CC(Cl)=CC(C(C)C)=C1NC(=O)NS(=O)(=O)C1=CC=CC(C(C)(C)O)=C1 YRSBLSHMKVQWHP-UHFFFAOYSA-N 0.000 claims description 3
WYOJYANQSVFZJC-UHFFFAOYSA-N 1-[4-chloro-2,6-di(propan-2-yl)phenyl]-3-[3-(methylsulfamoyl)phenyl]sulfonylurea Chemical compound CNS(=O)(=O)C1=CC=CC(S(=O)(=O)NC(=O)NC=2C(=CC(Cl)=CC=2C(C)C)C(C)C)=C1 WYOJYANQSVFZJC-UHFFFAOYSA-N 0.000 claims description 3
UTUTZQKQYZYYKW-UHFFFAOYSA-N 1-[4-fluoro-2,6-di(propan-2-yl)phenyl]-3-[3-(2-hydroxypropan-2-yl)phenyl]sulfonylurea Chemical compound CC(C)C1=CC(F)=CC(C(C)C)=C1NC(=O)NS(=O)(=O)C1=CC=CC(C(C)(C)O)=C1 UTUTZQKQYZYYKW-UHFFFAOYSA-N 0.000 claims description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
ZVGHRKGPUUKBPP-UHFFFAOYSA-N 1,2,3,5,6,7-hexahydro-s-indacene Chemical compound C1=C2CCCC2=CC2=C1CCC2 ZVGHRKGPUUKBPP-UHFFFAOYSA-N 0.000 claims 1
229940119178 Interleukin 1 receptor antagonist Drugs 0.000 abstract description 6
101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 abstract description 5
102000051628 Interleukin-1 receptor antagonist Human genes 0.000 abstract description 4
239000003407 interleukin 1 receptor blocking agent Substances 0.000 abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 164
239000000243 solution Substances 0.000 description 135
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
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VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
238000002360 preparation method Methods 0.000 description 67
238000006243 chemical reaction Methods 0.000 description 62
235000019439 ethyl acetate Nutrition 0.000 description 58
LYAWGVFUGRUFEO-UHFFFAOYSA-N 5-chloro-2-isocyanato-1,3-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC(Cl)=CC(C(C)C)=C1N=C=O LYAWGVFUGRUFEO-UHFFFAOYSA-N 0.000 description 48
239000007787 solid Substances 0.000 description 47
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
229960005261 aspartic acid Drugs 0.000 description 39
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
238000007792 addition Methods 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
210000004027 cell Anatomy 0.000 description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
239000002253 acid Substances 0.000 description 27
239000010410 layer Substances 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
102000004127 Cytokines Human genes 0.000 description 24
108090000695 Cytokines Proteins 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
FEUFNKALUGDEMQ-UHFFFAOYSA-N 2-isocyanato-1,3-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC=CC(C(C)C)=C1N=C=O FEUFNKALUGDEMQ-UHFFFAOYSA-N 0.000 description 23
238000003756 stirring Methods 0.000 description 23
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
BAQQPTXYEVIGBG-UHFFFAOYSA-N 1,3-bis(1h-pyrazol-5-yloxy)propan-2-one Chemical compound C=1C=NNC=1OCC(=O)COC1=CC=NN1 BAQQPTXYEVIGBG-UHFFFAOYSA-N 0.000 description 20
239000002585 base Substances 0.000 description 20
239000000047 product Substances 0.000 description 20
239000011541 reaction mixture Substances 0.000 description 20
230000002209 hydrophobic effect Effects 0.000 description 19
229940124530 sulfonamide Drugs 0.000 description 19
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 18
239000000460 chlorine Substances 0.000 description 18
238000004519 manufacturing process Methods 0.000 description 18
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 17
238000004809 thin layer chromatography Methods 0.000 description 17
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 16
229960004132 diethyl ether Drugs 0.000 description 16
239000003921 oil Substances 0.000 description 16
235000019198 oils Nutrition 0.000 description 16
239000008194 pharmaceutical composition Substances 0.000 description 16
108090000623 proteins and genes Proteins 0.000 description 16
DJWFRMONVAATNF-UHFFFAOYSA-N [3-(2,6-dichlorobenzoyl)oxy-2-oxopropyl] 2,6-dichlorobenzoate Chemical compound ClC1=CC=CC(Cl)=C1C(=O)OCC(=O)COC(=O)C1=C(Cl)C=CC=C1Cl DJWFRMONVAATNF-UHFFFAOYSA-N 0.000 description 15
239000000706 filtrate Substances 0.000 description 15
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238000010992 reflux Methods 0.000 description 15
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235000011152 sodium sulphate Nutrition 0.000 description 13
MJTPVXZNGZLGLN-UHFFFAOYSA-N 5-bromo-2-isocyanato-1,3-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC(Br)=CC(C(C)C)=C1N=C=O MJTPVXZNGZLGLN-UHFFFAOYSA-N 0.000 description 12
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150000003456 sulfonamides Chemical class 0.000 description 12
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QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
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239000002904 solvent Substances 0.000 description 11
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
125000004429 atom Chemical group 0.000 description 10
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230000002829 reductive effect Effects 0.000 description 10
239000011734 sodium Substances 0.000 description 10
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239000011780 sodium chloride Substances 0.000 description 9
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238000010792 warming Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000009736 wetting Methods 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Rheumatology (AREA)
Immunology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Pain & Pain Management (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

JP2001523022A 1999-09-14 2000-08-28 ＩＬ−１ｒａとＩＬ−１プロセシング・放出阻害化合物の併用療法 Pending JP2003509378A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US15401099P	1999-09-14	1999-09-14
US60/154,010		1999-09-14
PCT/IB2000/001192 WO2001019390A1 (en)	1999-09-14	2000-08-28	Combination treatment with il-1ra and diaryl sulphonyl urea compounds

Publications (1)

Publication Number	Publication Date
JP2003509378A true JP2003509378A (ja)	2003-03-11

Family

ID=22549650

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP2001523022A Pending JP2003509378A (ja)	1999-09-14	2000-08-28	ＩＬ−１ｒａとＩＬ−１プロセシング・放出阻害化合物の併用療法

Country Status (13)

Country	Link
EP (1)	EP1214087A1 (es)
JP (1)	JP2003509378A (es)
AR (1)	AR033650A1 (es)
AU (1)	AU6464400A (es)
BR (1)	BR0014003A (es)
CA (1)	CA2383026A1 (es)
CO (1)	CO5190701A1 (es)
EC (1)	ECSP003652A (es)
GT (1)	GT200000155A (es)
PA (1)	PA8502901A1 (es)
PE (1)	PE20010685A1 (es)
TN (1)	TNSN00183A1 (es)
WO (1)	WO2001019390A1 (es)

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JP2019515952A (ja) *	2016-04-18	2019-06-13	アイエフエムトレインコーポレイテッド	Ｎｌｒｐ活性に関連する状態を処置するための化合物および組成物
JP2020531453A (ja) *	2017-08-15	2020-11-05	インフレイゾームリミテッド	Ｎｌｒｐ３阻害剤としてのスルホニルウレアおよびスルホニルチオウレア
JP2022505525A (ja) *	2018-10-24	2022-01-14	ノバルティスアーゲー	Ｎｌｒｐ活性に関連する状態を治療するための化合物及び組成物

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WO2008129288A2 (en) *	2007-04-19	2008-10-30	Boehringer Ingelheim International Gmbh	Disulfonamides useful in the treatment of inflammation
PT3259253T (pt) *	2015-02-16	2020-03-11	Univ Queensland	Sulfonilureias e compostos relacionados e uso dos mesmos
BR112018016671A2 (pt)	2016-02-16	2018-12-26	The University Of Queensland	sulfonilureias e compostos relacionados e uso do mesmo
EP3851434A1 (en)	2017-01-23	2021-07-21	Genentech, Inc.	Chemical compounds as inhibitors of interleukin-1 activity
JP7072586B2 (ja)	2017-05-24	2022-05-20	ザユニバーシティオブクィーンズランド	新規な化合物及び使用
EP3634951B8 (en)	2017-06-09	2024-08-21	Zydus Lifesciences Limited	Novel substituted sulfoximine compounds
WO2019008029A1 (en)	2017-07-07	2019-01-10	Inflazome Limited	SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3
HUE057414T2 (hu)	2017-07-07	2022-05-28	Inflazome Ltd	Új szulfonamid karboxamid vegyületek
CA3068836A1 (en)	2017-07-24	2019-01-31	Novartis Inflammasome Research, Inc.	Compounds and compositions for treating conditions associated with nlrp activity
US11542255B2 (en)	2017-08-15	2023-01-03	Inflazome Limited	Sulfonylureas and sulfonylthioureas as NLRP3 inhibitors
EP3668840A1 (en)	2017-08-15	2020-06-24	Inflazome Limited	Novel sulfonamide carboxamide compounds
AU2018317800A1 (en)	2017-08-15	2020-02-13	Inflazome Limited	Novel sulfonamide carboxamide compounds
WO2019034693A1 (en)	2017-08-15	2019-02-21	Inflazome Limited	SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3
WO2019043610A1 (en)	2017-08-31	2019-03-07	Cadila Healthcare Limited	NEW SUBSTITUTED SULFONYLUREA DERIVATIVES
WO2019068772A1 (en)	2017-10-03	2019-04-11	Inflazome Limited	NEW COMPOUNDS
CN111315733A (zh)	2017-11-09	2020-06-19	英夫拉索姆有限公司	新颖磺酰胺甲酰胺化合物
US12221434B2 (en)	2017-11-09	2025-02-11	Inflazome Limited	Sulfonamide carboxamide compounds
US11530200B2 (en)	2018-03-02	2022-12-20	Inflazome Limited	Compounds
WO2019166619A1 (en)	2018-03-02	2019-09-06	Inflazome Limited	Novel compounds
EP3759090A1 (en)	2018-03-02	2021-01-06	Inflazome Limited	Novel compounds
EP3759078A1 (en)	2018-03-02	2021-01-06	Inflazome Limited	Novel compounds
EP3759102A1 (en)	2018-03-02	2021-01-06	Inflazome Limited	Novel compounds
US12168653B2 (en)	2018-03-02	2024-12-17	Inflazome Limited	Sulfonamide derivates as NLRP3 inhibitors
GB201806578D0 (en) *	2018-04-23	2018-06-06	Inflazome Ltd	Novel compound
CN112584899A (zh)	2018-07-03	2021-03-30	诺华股份有限公司	Nlrp调节剂
AU2019306658A1 (en)	2018-07-20	2021-01-07	F. Hoffmann-La Roche Ag	Sulfonimidamide compounds as inhibitors of interleukin-1 activity
SG11202012159TA (en)	2018-07-20	2021-01-28	Hoffmann La Roche	Sulfonylurea compounds as inhibitors of interleukin-1 activity
MX2021001754A (es)	2018-08-15	2021-04-19	Inflazome Ltd	Compuestos de sulfonamidaurea novedosos.
PL3911631T3 (pl)	2019-01-14	2025-04-28	Zydus Lifesciences Limited	Nowe podstawione pochodne sulfonylomocznika
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2000
- 2000-08-28 WO PCT/IB2000/001192 patent/WO2001019390A1/en not_active Ceased
- 2000-08-28 JP JP2001523022A patent/JP2003509378A/ja active Pending
- 2000-08-28 AU AU64644/00A patent/AU6464400A/en not_active Abandoned
- 2000-08-28 EP EP00951799A patent/EP1214087A1/en not_active Withdrawn
- 2000-08-28 CA CA002383026A patent/CA2383026A1/en not_active Abandoned
- 2000-08-28 BR BR0014003-1A patent/BR0014003A/pt not_active IP Right Cessation
- 2000-09-05 CO CO00066883A patent/CO5190701A1/es not_active Application Discontinuation
- 2000-09-11 PA PA20008502901A patent/PA8502901A1/es unknown
- 2000-09-12 PE PE2000000942A patent/PE20010685A1/es not_active Application Discontinuation
- 2000-09-12 AR ARP000104779A patent/AR033650A1/es not_active Application Discontinuation
- 2000-09-12 EC EC2000003652A patent/ECSP003652A/es unknown
- 2000-09-13 TN TNTNSN00183A patent/TNSN00183A1/fr unknown
- 2000-09-14 GT GT200000155A patent/GT200000155A/es unknown

Cited By (5)

* Cited by examiner, † Cited by third party
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JP2019515952A (ja) *	2016-04-18	2019-06-13	アイエフエムトレインコーポレイテッド	Ｎｌｒｐ活性に関連する状態を処置するための化合物および組成物
JP2019518071A (ja) *	2016-04-18	2019-06-27	アイエフエムトレインコーポレイテッド	Ｎｌｒｐ活性に関連する状態を処置するための化合物および組成物
JP7050751B2 (ja)	2016-04-18	2022-04-08	ノバルティスアーゲー	Ｎｌｒｐ活性に関連する状態を処置するための化合物および組成物
JP2020531453A (ja) *	2017-08-15	2020-11-05	インフレイゾームリミテッド	Ｎｌｒｐ３阻害剤としてのスルホニルウレアおよびスルホニルチオウレア
JP2022505525A (ja) *	2018-10-24	2022-01-14	ノバルティスアーゲー	Ｎｌｒｐ活性に関連する状態を治療するための化合物及び組成物

Also Published As

Publication number	Publication date
PA8502901A1 (es)	2002-02-21
CO5190701A1 (es)	2002-08-29
AR033650A1 (es)	2004-01-07
PE20010685A1 (es)	2001-07-03
WO2001019390A1 (en)	2001-03-22
GT200000155A (es)	2002-03-08
TNSN00183A1 (fr)	2005-11-10
BR0014003A (pt)	2002-05-21
ECSP003652A (es)	2002-04-23
CA2383026A1 (en)	2001-03-22
EP1214087A1 (en)	2002-06-19
AU6464400A (en)	2001-04-17

Publication	Publication Date	Title
JP2003509378A (ja)	2003-03-11	ＩＬ−１ｒａとＩＬ−１プロセシング・放出阻害化合物の併用療法
US6433009B1 (en)	2002-08-13	Sulfonyl urea derivatives and their use in the control of interleukin-1 activity
EP2588459B1 (en)	2017-03-01	Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory response
ES2899852T3 (es)	2022-03-15	Compuestos de N-(4-hidroxi-4-metil-ciclohexil)-4-fenil-bencenosulfonamida y N-(-4-hidroxi-4-metil-ciclohexil)-4-(2-piridil)-bencenosulfonamida y su uso terapéutico
KR20030017611A (ko)	2003-03-03	중성 엔도펩티다제 억제제로서 시클로펜틸-치환된글루타르아미드 유도체
JP2004522710A (ja)	2004-07-29	性機能障害の治療
Auvynet et al.	2016	ECL1i, d (LGTFLKC), a novel, small peptide that specifically inhibits CCL2‐dependent migration
US20030143230A1 (en)	2003-07-31	Combination of an IL-1/18 inhibitor with a TNF inhibitor for the treatment of inflammation
JP2004339232A (ja)	2004-12-02	ジアリールスルフォニルウレア化合物
US20050053603A1 (en)	2005-03-10	Drugs for liver diseases
WO2001026671A1 (en)	2001-04-19	Methods of treatment using dual matrix-metalloproteinase-2 and matrix metalloproteinase-9 inhibitors
EP1270554A1 (en)	2003-01-02	Sulfonyl urea derivatives and their use in the control of interleukin-1 activity
EP2945932B1 (en)	2018-11-21	Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory response
JP2002516605A (ja)	2002-06-04	糖尿病および肥満の治療のための併用療法
JPWO2002077226A1 (ja)	2004-07-15	プロスタグランジンｅｐ１受容体
JP2003012626A (ja)	2003-01-15	アルキルアミド化合物
JP2000086533A (ja)	2000-03-28	新規なアレルギー治療剤
US20050064519A1 (en)	2005-03-24	Methods of using GST-Omega-2
MXPA99007030A (es)	2000-02-02	Derivados de sulfonil urea
CZ312799A3 (cs)	2000-03-15	Přípravky pro modulaci reakce na kortikosteroidy
HK1073109A1 (zh)	2005-09-23	用於男性性功能障碍的治疗的药物组合物
HK1073109B (en)	2010-04-23	Pharmaceutical composition for treatment of male sexual dysfunction

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