JP2004503586A - 敗血症の治療方法 - Google Patents
敗血症の治療方法 Download PDFInfo
- Publication number
- JP2004503586A JP2004503586A JP2002511729A JP2002511729A JP2004503586A JP 2004503586 A JP2004503586 A JP 2004503586A JP 2002511729 A JP2002511729 A JP 2002511729A JP 2002511729 A JP2002511729 A JP 2002511729A JP 2004503586 A JP2004503586 A JP 2004503586A
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- JP
- Japan
- Prior art keywords
- methyl
- oxyacetic acid
- acid
- benzyl
- carbamoylcarbazol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- 206010040047 Sepsis Diseases 0.000 title claims abstract description 143
- 238000000034 method Methods 0.000 claims abstract description 141
- 150000001875 compounds Chemical class 0.000 claims description 267
- -1 C 2 -C 6 haloalkoxy Chemical group 0.000 claims description 131
- 239000000203 mixture Substances 0.000 claims description 99
- 239000003112 inhibitor Substances 0.000 claims description 97
- 206010053159 Organ failure Diseases 0.000 claims description 69
- 239000002253 acid Substances 0.000 claims description 66
- 238000004519 manufacturing process Methods 0.000 claims description 62
- 239000000651 prodrug Substances 0.000 claims description 62
- 229940002612 prodrug Drugs 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 47
- 238000011282 treatment Methods 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 125000005843 halogen group Chemical group 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 31
- 230000000694 effects Effects 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 239000012453 solvate Substances 0.000 claims description 28
- BHLXTPHDSZUFHR-UHFFFAOYSA-N varespladib Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC1=CC=CC=C1 BHLXTPHDSZUFHR-UHFFFAOYSA-N 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 25
- 230000002452 interceptive effect Effects 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 22
- 230000002378 acidificating effect Effects 0.000 claims description 22
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 22
- 125000005647 linker group Chemical group 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- FBGWHCFPQBQYNU-UHFFFAOYSA-N 2-(1-benzyl-2-methyl-3-oxamoylindol-4-yl)oxyacetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC1=CC=CC=C1 FBGWHCFPQBQYNU-UHFFFAOYSA-N 0.000 claims description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 230000000977 initiatory effect Effects 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 235000010290 biphenyl Nutrition 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 230000003287 optical effect Effects 0.000 claims description 10
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- CXAFWBHDYGONMZ-UHFFFAOYSA-N 2-[2-methyl-3-oxamoyl-1-[(3-phenylphenyl)methyl]indol-4-yl]oxyacetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC(C=1)=CC=CC=1C1=CC=CC=C1 CXAFWBHDYGONMZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 7
- KFJOAXDOAYZVOY-UHFFFAOYSA-N 2-[2-methyl-3-oxamoyl-1-[(2-phenylphenyl)methyl]indol-4-yl]oxyacetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC1=CC=CC=C1C1=CC=CC=C1 KFJOAXDOAYZVOY-UHFFFAOYSA-N 0.000 claims description 7
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 6
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 claims description 6
- 125000006766 (C2-C6) alkynyloxy group Chemical group 0.000 claims description 6
- HTSWKDOXMSFQPB-UHFFFAOYSA-N 8-ethoxy-7-methoxy-9H-carbazole-4-carboxamide Chemical compound N1C2=CC=CC(C(N)=O)=C2C2=C1C(OCC)=C(OC)C=C2 HTSWKDOXMSFQPB-UHFFFAOYSA-N 0.000 claims description 6
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 6
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 6
- 239000004305 biphenyl Substances 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 6
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 6
- 150000003555 thioacetals Chemical class 0.000 claims description 6
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 5
- CRXQYSQDOBKHNV-UHFFFAOYSA-N 2-[(9-benzyl-5-carbamoyl-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetic acid Chemical compound NC(=O)C1CCCC2=C1C1=C(OCC(O)=O)C=CC=C1N2CC1=CC=CC=C1 CRXQYSQDOBKHNV-UHFFFAOYSA-N 0.000 claims description 5
- ISRGSXVOKPRVIP-UHFFFAOYSA-N 9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole-4-carbohydrazide Chemical compound C12=CC(OC)=CC(OC)=C2C=2C(C(=O)NN)CCCC=2N1CC1=CC=CC=C1 ISRGSXVOKPRVIP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004694 alkoxyaminocarbonyl group Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 5
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 5
- UWZIPJAIHVSDQU-UHFFFAOYSA-N 2-(1-benzyl-2-cyclopropyl-3-oxamoylindol-4-yl)oxyacetic acid Chemical compound C=1C=CC=CC=1CN1C2=CC=CC(OCC(O)=O)=C2C(C(=O)C(=O)N)=C1C1CC1 UWZIPJAIHVSDQU-UHFFFAOYSA-N 0.000 claims description 4
- GWHFRTCCSTUDBC-UHFFFAOYSA-N 2-(1-benzyl-2-methyl-3-oxamoylindol-4-yl)oxypropanoic acid Chemical compound CC1=C(C(=O)C(N)=O)C=2C(OC(C)C(O)=O)=CC=CC=2N1CC1=CC=CC=C1 GWHFRTCCSTUDBC-UHFFFAOYSA-N 0.000 claims description 4
- AXRTZAZDPVBRMQ-UHFFFAOYSA-N 2-[1-[(2,6-dichlorophenyl)methyl]-2-methyl-3-oxamoylindol-4-yl]oxyacetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC1=C(Cl)C=CC=C1Cl AXRTZAZDPVBRMQ-UHFFFAOYSA-N 0.000 claims description 4
- NFFDUBFVBHVZQY-UHFFFAOYSA-N 2-[1-[(3-chlorophenyl)methyl]-2-ethyl-3-oxamoylindol-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC1=CC=CC(Cl)=C1 NFFDUBFVBHVZQY-UHFFFAOYSA-N 0.000 claims description 4
- OCZWKLXXLNWSDH-UHFFFAOYSA-N 2-[2-methyl-1-(naphthalen-1-ylmethyl)-3-oxamoylindol-4-yl]oxyacetic acid Chemical compound C1=CC=C2C(CN3C4=CC=CC(OCC(O)=O)=C4C(C(=O)C(N)=O)=C3C)=CC=CC2=C1 OCZWKLXXLNWSDH-UHFFFAOYSA-N 0.000 claims description 4
- VGOLBSXVJJOMNA-UHFFFAOYSA-N 2-[2-methyl-3-oxamoyl-1-[(4-phenylphenyl)methyl]indol-4-yl]oxyacetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1 VGOLBSXVJJOMNA-UHFFFAOYSA-N 0.000 claims description 4
- PCSBUIIMXNYHLA-UHFFFAOYSA-N 2-[3-oxamoyl-1-[(2-phenylphenyl)methyl]-2-propylindol-4-yl]oxyacetic acid Chemical compound CCCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC1=CC=CC=C1C1=CC=CC=C1 PCSBUIIMXNYHLA-UHFFFAOYSA-N 0.000 claims description 4
- CUSWQJGVEIICPH-UHFFFAOYSA-N 4-(1-benzyl-2-ethyl-3-oxamoylindol-5-yl)oxybutanoic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=CC(OCCCC(O)=O)=CC=C2N1CC1=CC=CC=C1 CUSWQJGVEIICPH-UHFFFAOYSA-N 0.000 claims description 4
- CGZZUCYZEGYRAT-UHFFFAOYSA-N 9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C12=CC(OC)=CC(OC)=C2C=2C(C(N)=O)CCCC=2N1CC1=CC=CC=C1 CGZZUCYZEGYRAT-UHFFFAOYSA-N 0.000 claims description 4
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 4
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 4
- GELSNBZFFJBDDC-UHFFFAOYSA-N 1-ethoxy-7-methoxy-2,3,4,9-tetrahydro-1H-carbazole-4-carboxamide Chemical compound C(C)OC1CCC(C=2C3=CC=C(C=C3NC1=2)OC)C(=O)N GELSNBZFFJBDDC-UHFFFAOYSA-N 0.000 claims description 3
- WVVBMMFAUGIIJM-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-1-chlorocarbazol-4-yl)oxyacetic acid Chemical compound C12=C(Cl)C=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 WVVBMMFAUGIIJM-UHFFFAOYSA-N 0.000 claims description 3
- LOEUKRWGLDWONT-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-1-fluorocarbazol-4-yl)oxyacetic acid Chemical compound C12=C(F)C=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 LOEUKRWGLDWONT-UHFFFAOYSA-N 0.000 claims description 3
- YIWKRIZOIPDUPO-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-1-methylcarbazol-4-yl)oxyacetic acid Chemical compound CC1=CC=C(OCC(O)=O)C(C2=C(C(N)=O)C=CC=C22)=C1N2CC1=CC=CC=C1 YIWKRIZOIPDUPO-UHFFFAOYSA-N 0.000 claims description 3
- XMNFDVRHTKIVQK-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-methoxycarbazol-4-yl)oxyacetic acid Chemical compound C=1C(OC)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 XMNFDVRHTKIVQK-UHFFFAOYSA-N 0.000 claims description 3
- PRAUIYBTAAOMCZ-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-methoxycarbazol-4-yl)oxypropanoic acid Chemical compound C=1C(OC)=CC(OC(C)C(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 PRAUIYBTAAOMCZ-UHFFFAOYSA-N 0.000 claims description 3
- AAYKHTVNNLLGLP-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-methylcarbazol-4-yl)oxyacetic acid Chemical compound C=1C(C)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 AAYKHTVNNLLGLP-UHFFFAOYSA-N 0.000 claims description 3
- PPBJJWDNJPGZPF-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-pentylcarbazol-4-yl)oxyacetic acid Chemical compound C=1C(CCCCC)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 PPBJJWDNJPGZPF-UHFFFAOYSA-N 0.000 claims description 3
- HCQNYAIKYZCDBC-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-propan-2-ylcarbazol-4-yl)oxyacetic acid Chemical compound C=1C(C(C)C)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 HCQNYAIKYZCDBC-UHFFFAOYSA-N 0.000 claims description 3
- UFJILQXRMNERCL-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoylcarbazol-4-yl)oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 UFJILQXRMNERCL-UHFFFAOYSA-N 0.000 claims description 3
- CXRULWWTHRSJSP-UHFFFAOYSA-N 2-[(9-benzyl-5-carbamoyl-1-chloro-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetic acid Chemical compound NC(=O)C1CCCC2=C1C1=C(OCC(O)=O)C=CC(Cl)=C1N2CC1=CC=CC=C1 CXRULWWTHRSJSP-UHFFFAOYSA-N 0.000 claims description 3
- LUURCHSHYLGPEG-UHFFFAOYSA-N 2-[(9-benzyl-5-carbamoyl-1-fluoro-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetic acid Chemical compound NC(=O)C1CCCC2=C1C1=C(OCC(O)=O)C=CC(F)=C1N2CC1=CC=CC=C1 LUURCHSHYLGPEG-UHFFFAOYSA-N 0.000 claims description 3
- OCQARBMASQXXGZ-UHFFFAOYSA-N 2-[(9-benzyl-5-carbamoyl-1-methyl-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetic acid Chemical compound C1=2C(C)=CC=C(OCC(O)=O)C=2C=2C(C(N)=O)CCCC=2N1CC1=CC=CC=C1 OCQARBMASQXXGZ-UHFFFAOYSA-N 0.000 claims description 3
- OXQCZJHYRFSEQM-UHFFFAOYSA-N 2-[5-carbamoyl-2-methyl-9-[(3-methylphenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound CC1=CC=CC(CN2C3=CC(C)=CC(OCC(O)=O)=C3C3=C(C(N)=O)C=CC=C32)=C1 OXQCZJHYRFSEQM-UHFFFAOYSA-N 0.000 claims description 3
- XQHXEBCEJGFYFD-UHFFFAOYSA-N 2-[5-carbamoyl-9-(cyclohexylmethyl)carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1CCCCC1 XQHXEBCEJGFYFD-UHFFFAOYSA-N 0.000 claims description 3
- YFTJSPAAYBFQNI-UHFFFAOYSA-N 2-[5-carbamoyl-9-(cyclopentylmethyl)carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1CCCC1 YFTJSPAAYBFQNI-UHFFFAOYSA-N 0.000 claims description 3
- PATZGVUJUUNVJN-UHFFFAOYSA-N 2-[5-carbamoyl-9-(naphthalen-1-ylmethyl)carbazol-4-yl]oxyacetic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C2=CC=CC(OCC(O)=O)=C2C2=C1C=CC=C2C(=O)N PATZGVUJUUNVJN-UHFFFAOYSA-N 0.000 claims description 3
- VZOLOKPKXHOJRH-UHFFFAOYSA-N 2-[5-carbamoyl-9-(pyridin-2-ylmethyl)carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=N1 VZOLOKPKXHOJRH-UHFFFAOYSA-N 0.000 claims description 3
- OJRRWHBSOZGENJ-UHFFFAOYSA-N 2-[5-carbamoyl-9-(pyridin-3-ylmethyl)carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CN=C1 OJRRWHBSOZGENJ-UHFFFAOYSA-N 0.000 claims description 3
- BLCNILYGCATZEH-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2,3-difluorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(F)=C1F BLCNILYGCATZEH-UHFFFAOYSA-N 0.000 claims description 3
- URFXAPISJQEWEH-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2,6-dichlorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=C(Cl)C=CC=C1Cl URFXAPISJQEWEH-UHFFFAOYSA-N 0.000 claims description 3
- VRMKRGKLFIJSNY-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2,6-difluorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=C(F)C=CC=C1F VRMKRGKLFIJSNY-UHFFFAOYSA-N 0.000 claims description 3
- HVKYETJTIUJSLB-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2-chlorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1Cl HVKYETJTIUJSLB-UHFFFAOYSA-N 0.000 claims description 3
- AKPJTFHUTNPVJJ-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2-cyanophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1C#N AKPJTFHUTNPVJJ-UHFFFAOYSA-N 0.000 claims description 3
- MQZAJAXITWPMFM-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2-fluorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1F MQZAJAXITWPMFM-UHFFFAOYSA-N 0.000 claims description 3
- UJSZZKJIGGAMHM-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2-methylphenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound CC1=CC=CC=C1CN1C2=CC=CC(C(N)=O)=C2C2=C(OCC(O)=O)C=CC=C21 UJSZZKJIGGAMHM-UHFFFAOYSA-N 0.000 claims description 3
- YAENEAAYRCUGQB-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3,5-dimethylphenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound CC1=CC(C)=CC(CN2C3=CC=CC(=C3C3=C(OCC(O)=O)C=CC=C32)C(N)=O)=C1 YAENEAAYRCUGQB-UHFFFAOYSA-N 0.000 claims description 3
- LCPAHBQVBUXTEZ-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-cyanophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(C#N)=C1 LCPAHBQVBUXTEZ-UHFFFAOYSA-N 0.000 claims description 3
- GSUXBSRHWJBQBV-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-fluorophenyl)methyl]-2-methylcarbazol-4-yl]oxyacetic acid Chemical compound C=1C(C)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC(F)=C1 GSUXBSRHWJBQBV-UHFFFAOYSA-N 0.000 claims description 3
- KWBVGNHCBQIRTN-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-fluorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(F)=C1 KWBVGNHCBQIRTN-UHFFFAOYSA-N 0.000 claims description 3
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- 125000002827 triflate group Chemical class FC(S(=O)(=O)O*)(F)F 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- DVBIMNUZCMCPRL-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O DVBIMNUZCMCPRL-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Peptides Or Proteins (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Apparatuses For Bulk Treatment Of Fruits And Vegetables And Apparatuses For Preparing Feeds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21892800P | 2000-07-14 | 2000-07-14 | |
| US25639800P | 2000-12-18 | 2000-12-18 | |
| PCT/US2001/016509 WO2002005796A2 (en) | 2000-07-14 | 2001-06-29 | Use of a spla2 inhibitor for the treatment of sepsis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2004503586A true JP2004503586A (ja) | 2004-02-05 |
Family
ID=26913393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002511729A Withdrawn JP2004503586A (ja) | 2000-07-14 | 2001-06-29 | 敗血症の治療方法 |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1303262A2 (zh) |
| JP (1) | JP2004503586A (zh) |
| CN (1) | CN1450893A (zh) |
| AU (1) | AU2001272915A1 (zh) |
| BR (1) | BR0112460A (zh) |
| CA (1) | CA2413582A1 (zh) |
| WO (1) | WO2002005796A2 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010137484A1 (ja) * | 2009-05-28 | 2010-12-02 | 石原産業株式会社 | ジアミノトリフルオロメチルピリジン誘導体を含有する抗ショック剤 |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3693063A1 (en) * | 2019-02-06 | 2020-08-12 | Diaccurate | Methods and compositions for treating cancer |
| CN112022846B (zh) * | 2020-09-23 | 2021-10-08 | 吕奔 | 一种吲哚啉衍生物在制备治疗脓毒症药物中的应用 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL109311A0 (en) * | 1993-04-16 | 1994-07-31 | Lilly Co Eli | 1H-indole-3-acetamide sPla2 inhibitors |
| IL109309A (en) * | 1993-04-16 | 2000-06-29 | Lilly Co Eli | 1-H-indole-3-acetic acid hydrazide SPLA2 inhibitors and pharmaceutical compositions containing them |
| ES2179088T3 (es) * | 1994-04-01 | 2003-01-16 | Lilly Co Eli | Inhibidores de flsa2 1h-indol-3-glioxilamida. |
| US5641800A (en) * | 1994-07-21 | 1997-06-24 | Eli Lilly And Company | 1H-indole-1-functional sPLA2 inhibitors |
| CA2264020A1 (en) * | 1996-08-26 | 1998-03-05 | Jean Bemis | Inhibitors of phospholipase enzymes |
| EP0987250A4 (en) * | 1997-02-20 | 2000-12-06 | Shionogi & Co | INDOLDICARBONIC ACID DERIVATIVES |
| EP1039911B1 (en) * | 1997-10-27 | 2005-05-25 | Eli Lilly And Company | MORPHOLINO-N-ETHYL ESTER PRODRUGS OF INDOLE sPLA 2 INHIBITORS |
| WO1999021545A1 (en) * | 1997-10-27 | 1999-05-06 | Eli Lilly And Company | ISOPROPYL ESTER PRODRUGS OF INDOLE sPLA2 INHIBITORS |
| CA2309135A1 (en) * | 1997-10-27 | 1999-05-06 | Michael Lyle Denney | N,n-diethylglycolamido ester prodrugs of indole spla2 inhibitors |
| EE200000522A (et) * | 1998-02-25 | 2002-02-15 | Genetics Institute, Inc. | Fosfolipaas A2 ensüümi inhibiitor, seda sisaldav farmatseutiline kompositsioon ning meetod fosfolipaasensüümi toime pärssimiseks |
| KR20010034552A (ko) * | 1998-03-03 | 2001-04-25 | 요시히코 시오노 | 포스포리파제 저해제인 소듐[[3-(2-아미노-1,2-디옥소에틸)-2-에틸-1-(페닐메틸)-1ｈ-인돌-4-일]옥시]아세테이트를 포함하는 약학적 조성물 |
| ID23219A (id) * | 1998-04-17 | 2000-03-30 | Lilly Co Eli | Trisiklik tersubstitusi |
| DZ2769A1 (fr) * | 1998-04-17 | 2003-12-01 | Lilly Co Eli | Composés tricycliques substitués. |
| DE69921314T2 (de) * | 1998-05-01 | 2006-02-09 | Eli Lilly And Co., Indianapolis | INHIBITORISCHE ESTER FÜR sPLA 2 |
| AU5331499A (en) * | 1998-08-03 | 2000-02-28 | Eli Lilly And Company | Indole spla2 inhibitors |
| WO2000007590A1 (en) * | 1998-08-03 | 2000-02-17 | Eli Lilly And Company | INDOLE sPLA2 INHIBITORS |
| AU1940800A (en) * | 1998-12-21 | 2000-07-12 | Eli Lilly And Company | Combination therapy for the treatment of sepsis |
| EP1144305A4 (en) * | 1998-12-22 | 2004-11-10 | Lilly Co Eli | NEW sPLA 2 INHIBITORS |
-
2001
- 2001-06-29 CA CA002413582A patent/CA2413582A1/en not_active Abandoned
- 2001-06-29 EP EP01952123A patent/EP1303262A2/en not_active Withdrawn
- 2001-06-29 JP JP2002511729A patent/JP2004503586A/ja not_active Withdrawn
- 2001-06-29 AU AU2001272915A patent/AU2001272915A1/en not_active Abandoned
- 2001-06-29 CN CN01812765A patent/CN1450893A/zh active Pending
- 2001-06-29 BR BR0112460-9A patent/BR0112460A/pt not_active Application Discontinuation
- 2001-06-29 WO PCT/US2001/016509 patent/WO2002005796A2/en not_active Application Discontinuation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010137484A1 (ja) * | 2009-05-28 | 2010-12-02 | 石原産業株式会社 | ジアミノトリフルオロメチルピリジン誘導体を含有する抗ショック剤 |
| JP2011006384A (ja) * | 2009-05-28 | 2011-01-13 | Ishihara Sangyo Kaisha Ltd | ジアミノトリフルオロメチルピリジン誘導体を含有する抗ショック剤 |
| US8604212B2 (en) | 2009-05-28 | 2013-12-10 | Ishihara Sangyo Kaisha, Ltd. | Anti-shock agent comprising diaminotrifluoromethylpyridine derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002005796A2 (en) | 2002-01-24 |
| WO2002005796A3 (en) | 2002-09-06 |
| EP1303262A2 (en) | 2003-04-23 |
| CA2413582A1 (en) | 2002-01-24 |
| AU2001272915A1 (en) | 2002-01-30 |
| CN1450893A (zh) | 2003-10-22 |
| BR0112460A (pt) | 2003-07-22 |
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