HRP20000744A2 - Succinamide inhibitors of interleukin-1beta converting enzyme - Google Patents
Succinamide inhibitors of interleukin-1beta converting enzyme Download PDFInfo
- Publication number
- HRP20000744A2 HRP20000744A2 HR20000744A HRP20000744A HRP20000744A2 HR P20000744 A2 HRP20000744 A2 HR P20000744A2 HR 20000744 A HR20000744 A HR 20000744A HR P20000744 A HRP20000744 A HR P20000744A HR P20000744 A2 HRP20000744 A2 HR P20000744A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- oxo
- butyrylamino
- dimethyl
- hept
- Prior art date
Links
- 108090000426 Caspase-1 Proteins 0.000 title claims description 11
- 239000003112 inhibitor Substances 0.000 title description 16
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 99
- -1 3-phenyl-propylcarbamoyl Chemical group 0.000 claims description 75
- 238000000034 method Methods 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 208000027866 inflammatory disease Diseases 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 12
- 206010040070 Septic Shock Diseases 0.000 claims description 11
- 230000036303 septic shock Effects 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 10
- 208000004429 Bacillary Dysentery Diseases 0.000 claims description 9
- 206010063837 Reperfusion injury Diseases 0.000 claims description 9
- 206010040550 Shigella infections Diseases 0.000 claims description 9
- 201000005113 shigellosis Diseases 0.000 claims description 9
- 125000001072 heteroaryl group Chemical class 0.000 claims description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- FYCCIUJXABECOW-UHFFFAOYSA-N 3-[[4-[2-(benzimidazol-1-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound C1=CC=C2N(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)C=NC2=C1 FYCCIUJXABECOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- OMUHWSWPEYIRFO-UHFFFAOYSA-N 3-[[4-[2-(1-methylindol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound C1=CC=C2C(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)=CN(C)C2=C1 OMUHWSWPEYIRFO-UHFFFAOYSA-N 0.000 claims description 5
- LZGZUQCAIMRUJK-UHFFFAOYSA-N 3-[[4-[methyl-[2-(1-methylindol-3-yl)ethyl]amino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound C1=CC=C2C(CCN(C)C(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)=CN(C)C2=C1 LZGZUQCAIMRUJK-UHFFFAOYSA-N 0.000 claims description 5
- YJGXGSUZLSGBPJ-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-[2-(1h-indol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1=CC=C2C(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CNC2=C1 YJGXGSUZLSGBPJ-UHFFFAOYSA-N 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 206010030113 Oedema Diseases 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- MZUVURCHWDQBDF-UHFFFAOYSA-N 3-[[2-methyl-4-oxo-4-(2-phenylethylamino)butanoyl]amino]-4-oxo-5-(2-phenylethylsulfonylamino)pentanoic acid Chemical compound C=1C=CC=CC=1CCS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C)CC(=O)NCCC1=CC=CC=C1 MZUVURCHWDQBDF-UHFFFAOYSA-N 0.000 claims description 4
- ALSHHEZZTBJVFO-UHFFFAOYSA-N 3-cyano-3-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]propanoic acid Chemical compound OC(=O)CC(C#N)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 ALSHHEZZTBJVFO-UHFFFAOYSA-N 0.000 claims description 4
- ZAIVMSZGHRKJDG-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-(2-naphthalen-2-ylethylamino)-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1=CC=CC2=CC(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CC=C21 ZAIVMSZGHRKJDG-UHFFFAOYSA-N 0.000 claims description 4
- YVDYEVYYQUUDIS-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-[2-(1-methylindol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1=CC=C2C(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CN(C)C2=C1 YVDYEVYYQUUDIS-UHFFFAOYSA-N 0.000 claims description 4
- XWALDGGHYAEDCL-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-[2-(7-methyl-1h-indol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1=CC=C2C(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CNC2=C1C XWALDGGHYAEDCL-UHFFFAOYSA-N 0.000 claims description 4
- IXUARISNSRBUJD-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-[3-(4-hydroxyphenyl)propylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCCC1=CC=C(O)C=C1 IXUARISNSRBUJD-UHFFFAOYSA-N 0.000 claims description 4
- SNISAOKKKWUGRW-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-2-propan-2-yl-4-(2-pyridin-4-ylethylamino)butanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCC1=CC=NC=C1 SNISAOKKKWUGRW-UHFFFAOYSA-N 0.000 claims description 4
- OQVPDXQMYPUZFW-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-2-propan-2-yl-4-(3-pyridin-3-ylpropylamino)butanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCCC1=CC=CN=C1 OQVPDXQMYPUZFW-UHFFFAOYSA-N 0.000 claims description 4
- IPSVFQYSPOCYMN-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-2-propan-2-yl-4-(3-pyridin-4-ylpropylamino)butanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCCC1=CC=NC=C1 IPSVFQYSPOCYMN-UHFFFAOYSA-N 0.000 claims description 4
- BYZLVVPBXIRECB-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-2-propan-2-yl-4-(3-quinolin-2-ylpropylamino)butanoyl]amino]pentanoic acid Chemical compound C1=CC=CC2=NC(CCCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CC=C21 BYZLVVPBXIRECB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 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
- SXYYPOZRVFSDMZ-IRXDYDNUSA-N (3s)-4-oxo-3-[[(2s)-4-oxo-4-(3-phenylpropylamino)-2-propan-2-ylbutanoyl]amino]butanoic acid Chemical compound OC(=O)C[C@@H](C=O)NC(=O)[C@H](C(C)C)CC(=O)NCCCC1=CC=CC=C1 SXYYPOZRVFSDMZ-IRXDYDNUSA-N 0.000 claims description 3
- UXUNULFUFXVARP-UHFFFAOYSA-N 3-[(4-amino-4-oxo-2-propan-2-ylbutanoyl)amino]-4-oxo-5-(2-phenylethylsulfonylamino)pentanoic acid Chemical compound NC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CCC1=CC=CC=C1 UXUNULFUFXVARP-UHFFFAOYSA-N 0.000 claims description 3
- CFORYPHSPKDMEB-UHFFFAOYSA-N 3-[(4-amino-4-oxo-2-propan-2-ylbutanoyl)amino]-5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxopentanoic acid Chemical compound C1CC2CC(=O)C1(CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(CC(N)=O)C(C)C)C2(C)C CFORYPHSPKDMEB-UHFFFAOYSA-N 0.000 claims description 3
- XRUJXLILCDQUBR-UHFFFAOYSA-N 3-[[4-(2-indazol-1-ylethylamino)-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound C1=CC=C2N(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)N=CC2=C1 XRUJXLILCDQUBR-UHFFFAOYSA-N 0.000 claims description 3
- IPQQKJSNVGVBSQ-UHFFFAOYSA-N 3-[[4-[2-(5,6-dichlorobenzimidazol-1-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound ClC1=C(Cl)C=C2N(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)C=NC2=C1 IPQQKJSNVGVBSQ-UHFFFAOYSA-N 0.000 claims description 3
- XBMQWXWDFFGISD-UHFFFAOYSA-N 3-[[4-[2-(5,6-dimethylbenzimidazol-1-yl)ethyl-methylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound CC1=C(C)C=C2N(CCN(C)C(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)C=NC2=C1 XBMQWXWDFFGISD-UHFFFAOYSA-N 0.000 claims description 3
- ZRBDUXYZPRRPED-UHFFFAOYSA-N 3-[[4-[2-(5-fluoro-1-methylindol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound C1=C(F)C=C2C(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)=CN(C)C2=C1 ZRBDUXYZPRRPED-UHFFFAOYSA-N 0.000 claims description 3
- FWLJQHZRZYCOEE-UHFFFAOYSA-N 3-[[4-[2-(benzimidazol-1-yl)ethyl-methylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound C1=CC=C2N(CCN(C)C(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)C=NC2=C1 FWLJQHZRZYCOEE-UHFFFAOYSA-N 0.000 claims description 3
- DHICQUDFEFIXRL-UHFFFAOYSA-N 3-[[4-[2-(benzotriazol-1-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound C1=CC=C2N(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)N=NC2=C1 DHICQUDFEFIXRL-UHFFFAOYSA-N 0.000 claims description 3
- GPJDCEFHOLNTRA-UHFFFAOYSA-N 3-[[4-[methyl-[2-(2-methylbenzimidazol-1-yl)ethyl]amino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound C1=CC=C2N(CCN(C)C(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)C(C)=NC2=C1 GPJDCEFHOLNTRA-UHFFFAOYSA-N 0.000 claims description 3
- RMQOYZHBEKJFSG-UHFFFAOYSA-N 4-oxo-3-[[4-oxo-2-propan-2-yl-4-[3-(3,4,5-trimethoxyphenyl)propylamino]butanoyl]amino]butanoic acid Chemical compound COC1=CC(CCCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)=CC(OC)=C1OC RMQOYZHBEKJFSG-UHFFFAOYSA-N 0.000 claims description 3
- WVTPLZYSAAVPBQ-UHFFFAOYSA-N 4-oxo-3-[[4-oxo-4-(2-phenylethylamino)-2-propan-2-ylbutanoyl]amino]-5-(2-phenylethylsulfonylamino)pentanoic acid Chemical compound C=1C=CC=CC=1CCS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCC1=CC=CC=C1 WVTPLZYSAAVPBQ-UHFFFAOYSA-N 0.000 claims description 3
- ZUFPMJKQYAGYHR-UHFFFAOYSA-N 4-oxo-3-[[4-oxo-4-(2-phenylethylamino)-2-propan-2-ylbutanoyl]amino]-5-(3-phenylpropylsulfanyl)pentanoic acid Chemical compound C=1C=CC=CC=1CCCSCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCC1=CC=CC=C1 ZUFPMJKQYAGYHR-UHFFFAOYSA-N 0.000 claims description 3
- YLAFLTZOFXGZAF-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-[2-(6-fluoro-1h-indol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound FC1=CC=C2C(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CNC2=C1 YLAFLTZOFXGZAF-UHFFFAOYSA-N 0.000 claims description 3
- GMFVFYZTQIAOOM-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-2-propan-2-yl-4-[2-(2h-tetrazol-5-yl)ethylamino]butanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCC=1N=NNN=1 GMFVFYZTQIAOOM-UHFFFAOYSA-N 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims description 3
- MHEIOOYEBOEOJP-UHFFFAOYSA-N ethyl 3-cyano-3-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]propanoate Chemical compound CCOC(=O)CC(C#N)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 MHEIOOYEBOEOJP-UHFFFAOYSA-N 0.000 claims description 3
- WTFFVGDFKJYHDS-UHFFFAOYSA-N ethyl 4-oxo-3-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]butanoate Chemical compound CCOC(=O)CC(C=O)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 WTFFVGDFKJYHDS-UHFFFAOYSA-N 0.000 claims description 3
- 125000001041 indolyl group Chemical class 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- NJKSHRDVWWICQC-UHFFFAOYSA-N n'-(2-anilinoethyl)-n-(2-ethoxy-5-oxooxolan-3-yl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCNC1=CC=CC=C1 NJKSHRDVWWICQC-UHFFFAOYSA-N 0.000 claims description 3
- MSCCZOCHBDKJSP-UHFFFAOYSA-N n'-[2-(5,6-dichlorobenzimidazol-1-yl)ethyl]-n-(2-ethoxy-5-oxooxolan-3-yl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCN1C2=CC(Cl)=C(Cl)C=C2N=C1 MSCCZOCHBDKJSP-UHFFFAOYSA-N 0.000 claims description 3
- SNLWGVISANRFPN-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-2-propan-2-yl-n'-[3-(3,4,5-trimethoxyphenyl)propyl]butanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCCC1=CC(OC)=C(OC)C(OC)=C1 SNLWGVISANRFPN-UHFFFAOYSA-N 0.000 claims description 3
- IDGJYNGQBBSSIG-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-(2-indazol-1-ylethyl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCN1C2=CC=CC=C2C=N1 IDGJYNGQBBSSIG-UHFFFAOYSA-N 0.000 claims description 3
- KLURNRGOXJDOCO-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-(2-indol-1-ylethyl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCN1C2=CC=CC=C2C=C1 KLURNRGOXJDOCO-UHFFFAOYSA-N 0.000 claims description 3
- SAOHRZFSCGURLX-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-(2-phenylethyl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCC1=CC=CC=C1 SAOHRZFSCGURLX-UHFFFAOYSA-N 0.000 claims description 3
- JXAMDESAKCPXDA-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-[2-(1-methylindol-3-yl)ethyl]-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCC1=CN(C)C2=CC=CC=C12 JXAMDESAKCPXDA-UHFFFAOYSA-N 0.000 claims description 3
- MPEBATMSAGYWEI-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-[2-(2-methylbenzimidazol-1-yl)ethyl]-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCN1C2=CC=CC=C2N=C1C MPEBATMSAGYWEI-UHFFFAOYSA-N 0.000 claims description 3
- MGOBBNLLQAZKKG-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-[2-(5-fluoro-1h-indol-3-yl)ethyl]-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCC1=CNC2=CC=C(F)C=C12 MGOBBNLLQAZKKG-UHFFFAOYSA-N 0.000 claims description 3
- QPGPSSOPHMJFHX-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-[2-(6-fluoro-1h-indol-3-yl)ethyl]-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCC1=CNC2=CC(F)=CC=C12 QPGPSSOPHMJFHX-UHFFFAOYSA-N 0.000 claims description 3
- YDWTYXJTNLPSNQ-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-[2-(6-methoxy-1h-indol-3-yl)ethyl]-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCC1=CNC2=CC(OC)=CC=C12 YDWTYXJTNLPSNQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- YSZOECXLIFTNLN-UHFFFAOYSA-N 3-[[4-[2-(5,6-dimethylbenzimidazol-1-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound CC1=C(C)C=C2N(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O)C=NC2=C1 YSZOECXLIFTNLN-UHFFFAOYSA-N 0.000 claims description 2
- PXGWXDCBTHYXQA-UHFFFAOYSA-N 3-[[4-[2-(5-acetyl-1h-indol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxopentanoic acid Chemical compound C1=C(C(C)=O)C=C2C(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CNC2=C1 PXGWXDCBTHYXQA-UHFFFAOYSA-N 0.000 claims description 2
- AFGJEEOPXMSIOD-UHFFFAOYSA-N 3-[[4-[2-(benzimidazol-1-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxopentanoic acid Chemical compound C1=NC2=CC=CC=C2N1CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC1(C2(C)C)C(=O)CC2CC1 AFGJEEOPXMSIOD-UHFFFAOYSA-N 0.000 claims description 2
- XETWXTRPXCSOBF-UHFFFAOYSA-N 3-[[4-[methyl(2-phenoxyethyl)amino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CC(C=O)NC(=O)C(C(C)C)CC(=O)N(C)CCOC1=CC=CC=C1 XETWXTRPXCSOBF-UHFFFAOYSA-N 0.000 claims description 2
- BEXWSXWFQDNGQE-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[2-ethyl-4-[2-(1-methylindol-3-yl)ethylamino]-4-oxobutanoyl]amino]-4-oxopentanoic acid Chemical compound C1=CC=C2C(CCNC(=O)CC(CC)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CN(C)C2=C1 BEXWSXWFQDNGQE-UHFFFAOYSA-N 0.000 claims description 2
- XGKBLVBCTNGOIU-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[2-ethyl-4-oxo-4-(3-phenylpropylamino)butanoyl]amino]-4-oxopentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(CC)CC(=O)NCCCC1=CC=CC=C1 XGKBLVBCTNGOIU-UHFFFAOYSA-N 0.000 claims description 2
- SISSKRFKMPWYDO-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-(3-naphthalen-1-ylpropylamino)-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1=CC=C2C(CCCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CC=CC2=C1 SISSKRFKMPWYDO-UHFFFAOYSA-N 0.000 claims description 2
- ZDWCTMZEINUOOA-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-(3-naphthalen-2-ylpropylamino)-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1=CC=CC2=CC(CCCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34C(CC(CC3)C4(C)C)=O)=CC=C21 ZDWCTMZEINUOOA-UHFFFAOYSA-N 0.000 claims description 2
- XJTVMTWARLAZRX-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-(hydroxyamino)-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1CC2CC(=O)C1(CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(CC(=O)NO)C(C)C)C2(C)C XJTVMTWARLAZRX-UHFFFAOYSA-N 0.000 claims description 2
- UDFCESFAOARNEL-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-[methyl(2-phenylethyl)amino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)N(C)CCC1=CC=CC=C1 UDFCESFAOARNEL-UHFFFAOYSA-N 0.000 claims description 2
- BYIDKTBZJNUAFD-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 BYIDKTBZJNUAFD-UHFFFAOYSA-N 0.000 claims description 2
- XRAWHIWHCVNVJO-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-4-(2-phenylethylamino)-2-propan-2-ylbutanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCC1=CC=CC=C1 XRAWHIWHCVNVJO-UHFFFAOYSA-N 0.000 claims description 2
- DQCMRJPHBFENEP-UHFFFAOYSA-N 5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-4-(3-phenylpropylamino)-2-propan-2-ylbutanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCCC1=CC=CC=C1 DQCMRJPHBFENEP-UHFFFAOYSA-N 0.000 claims description 2
- VUYXWAPVLXXLPC-UHFFFAOYSA-N 5-[(7,7-dimethyl-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[4-[2-(1h-indol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid Chemical compound C1=CC=C2C(CCNC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C(=O)CNS(=O)(=O)CC34CCC(CC3)C4(C)C)=CNC2=C1 VUYXWAPVLXXLPC-UHFFFAOYSA-N 0.000 claims description 2
- VDFUVPSQHGRAKA-UHFFFAOYSA-N 5-[(7,7-dimethyl-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-4-(2-phenylethylamino)-2-propan-2-ylbutanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CCC12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCC1=CC=CC=C1 VDFUVPSQHGRAKA-UHFFFAOYSA-N 0.000 claims description 2
- NBCBUZSWRPYDGX-UHFFFAOYSA-N 5-[(7,7-dimethyl-4-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-4-oxo-3-[[4-oxo-4-(3-phenylpropylamino)-2-propan-2-ylbutanoyl]amino]pentanoic acid Chemical compound C1CC(C2(C)C)CCC12CS(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCCC1=CC=CC=C1 NBCBUZSWRPYDGX-UHFFFAOYSA-N 0.000 claims description 2
- JYNYDTMJAHHXBP-UHFFFAOYSA-N N'-[2-(benzotriazol-1-yl)ethyl]-N-(2-ethoxy-5-oxooxolan-3-yl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(CC(=O)NCCn1nnc2ccccc12)C(C)C JYNYDTMJAHHXBP-UHFFFAOYSA-N 0.000 claims description 2
- XNDWSTRDEXTYMB-UHFFFAOYSA-N n'-[2-(benzimidazol-1-yl)ethyl]-n-(2-ethoxy-5-oxooxolan-3-yl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCN1C2=CC=CC=C2N=C1 XNDWSTRDEXTYMB-UHFFFAOYSA-N 0.000 claims description 2
- BURLKYAULPTGPZ-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-(2-phenoxyethyl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 BURLKYAULPTGPZ-UHFFFAOYSA-N 0.000 claims description 2
- UGTYMRFUKGANOY-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-(4-phenylbutyl)-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCCCC1=CC=CC=C1 UGTYMRFUKGANOY-UHFFFAOYSA-N 0.000 claims description 2
- BEPIPOUSAJXMKY-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-[2-(1h-indol-3-yl)ethyl]-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCC1=CNC2=CC=CC=C12 BEPIPOUSAJXMKY-UHFFFAOYSA-N 0.000 claims description 2
- KQLZHFALCMMQTO-UHFFFAOYSA-N n-(2-ethoxy-5-oxooxolan-3-yl)-n'-[2-(7-methyl-1h-indol-3-yl)ethyl]-2-propan-2-ylbutanediamide Chemical compound CCOC1OC(=O)CC1NC(=O)C(C(C)C)CC(=O)NCCC1=CNC2=C(C)C=CC=C12 KQLZHFALCMMQTO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 115
- 239000007787 solid Substances 0.000 description 106
- 239000000243 solution Substances 0.000 description 99
- 238000004458 analytical method Methods 0.000 description 80
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
- 235000019439 ethyl acetate Nutrition 0.000 description 59
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 39
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 37
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- 239000000284 extract Substances 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000012267 brine Substances 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 18
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical class [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 15
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000007836 KH2PO4 Substances 0.000 description 7
- 239000007832 Na2SO4 Substances 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 7
- 235000019796 monopotassium phosphate Nutrition 0.000 description 7
- 239000012047 saturated solution Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000001384 succinic acid Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 5
- AWJWWPYNMMJWAJ-ZDUSSCGKSA-N (2s)-4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoic acid Chemical compound CC(C)[C@@H](C(O)=O)CC(=O)NCCOC1=CC=CC=C1 AWJWWPYNMMJWAJ-ZDUSSCGKSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 235000010357 aspartame Nutrition 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- MFDUJNOPQALQRV-GJZGRUSLSA-N (2S)-2-[[(2S)-4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)CC(=O)NCCOC1=CC=CC=C1 MFDUJNOPQALQRV-GJZGRUSLSA-N 0.000 description 3
- QMCJVFYCDSYHGW-QMMMGPOBSA-N (2s)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-propan-2-ylbutanoic acid Chemical compound CC(C)[C@@H](C(O)=O)CC(=O)OC(C)(C)C QMCJVFYCDSYHGW-QMMMGPOBSA-N 0.000 description 3
- LQQKDSXCDXHLLF-UHFFFAOYSA-N 1,3-dibromopropan-2-one Chemical compound BrCC(=O)CBr LQQKDSXCDXHLLF-UHFFFAOYSA-N 0.000 description 3
- FGOJCPKOOGIRPA-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 5-oxoazepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O FGOJCPKOOGIRPA-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
- CWARULQNYJKOMP-LURJTMIESA-N 4-o-tert-butyl 1-o-methyl (2s)-2-aminobutanedioate Chemical compound COC(=O)[C@@H](N)CC(=O)OC(C)(C)C CWARULQNYJKOMP-LURJTMIESA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- KSPQCEBUKAPJIJ-UHFFFAOYSA-N CC(C)(C)OC(=O)NS(=O)=O Chemical compound CC(C)(C)OC(=O)NS(=O)=O KSPQCEBUKAPJIJ-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 102100029855 Caspase-3 Human genes 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- NMPVEAUIHMEAQP-UHFFFAOYSA-N alpha-bromo-acetaldehyde Natural products BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 229960003130 interferon gamma Drugs 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- RKAFKUROUOLPOL-YFKPBYRVSA-N (2s)-2-propan-2-ylbutanedioic acid Chemical compound CC(C)[C@@H](C(O)=O)CC(O)=O RKAFKUROUOLPOL-YFKPBYRVSA-N 0.000 description 2
- VIBHBBGMHZXYOR-AWEZNQCLSA-N (2s)-4-oxo-4-(3-phenylpropylamino)-2-propan-2-ylbutanoic acid Chemical compound CC(C)[C@@H](C(O)=O)CC(=O)NCCCC1=CC=CC=C1 VIBHBBGMHZXYOR-AWEZNQCLSA-N 0.000 description 2
- YDPNOCSPPGFBPX-XNHCRPTKSA-N (3s)-3-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-4-(4-nitroanilino)-4-oxobutanoic acid Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)NC(C)=O)C1=CC=C(O)C=C1 YDPNOCSPPGFBPX-XNHCRPTKSA-N 0.000 description 2
- VCSZRMQVTCRUIN-LBPRGKRZSA-N (3s)-4-methyl-3-phenylmethoxycarbonylpentanoic acid Chemical compound OC(=O)C[C@@H](C(C)C)C(=O)OCC1=CC=CC=C1 VCSZRMQVTCRUIN-LBPRGKRZSA-N 0.000 description 2
- XZFDLJWHIQWPEO-HOTGVXAUSA-N (3s)-5-bromo-4-oxo-3-[[(2s)-4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]pentanoic acid Chemical compound OC(=O)C[C@@H](C(=O)CBr)NC(=O)[C@H](C(C)C)CC(=O)NCCOC1=CC=CC=C1 XZFDLJWHIQWPEO-HOTGVXAUSA-N 0.000 description 2
- TZFXVYWRBTZTML-SECBINFHSA-N (4s)-3-(3-methylbutanoyl)-4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound CC(C)CC(=O)N1[C@@H](C(C)C)COC1=O TZFXVYWRBTZTML-SECBINFHSA-N 0.000 description 2
- YBUPWRYTXGAWJX-RXMQYKEDSA-N (4s)-4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound CC(C)[C@H]1COC(=O)N1 YBUPWRYTXGAWJX-RXMQYKEDSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- HRXZWYOZDGUIOE-UHFFFAOYSA-N 2-[[2-methyl-4-oxo-4-(2-phenylethylamino)butanoyl]amino]-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid Chemical compound CC(C)(C)OC(=O)CC(C(O)=O)NC(=O)C(C)CC(=O)NCCC1=CC=CC=C1 HRXZWYOZDGUIOE-UHFFFAOYSA-N 0.000 description 2
- MFDUJNOPQALQRV-UHFFFAOYSA-N 2-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]butanedioic acid Chemical compound OC(=O)CC(C(O)=O)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 MFDUJNOPQALQRV-UHFFFAOYSA-N 0.000 description 2
- AUIXDUUVVVXBRB-UHFFFAOYSA-N 2-methyl-4-oxo-4-(2-phenylethylamino)butanoic acid Chemical compound OC(=O)C(C)CC(=O)NCCC1=CC=CC=C1 AUIXDUUVVVXBRB-UHFFFAOYSA-N 0.000 description 2
- UUEFVQPMPCCGHW-UHFFFAOYSA-N 2-methylidene-4-oxo-4-(2-phenylethylamino)butanoic acid Chemical compound OC(=O)C(=C)CC(=O)NCCC1=CC=CC=C1 UUEFVQPMPCCGHW-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- PMVGETHEZYTKFP-UHFFFAOYSA-N 3-[[4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid Chemical compound CC(C)(C)OC(=O)CC(C(C)C)C(=O)NC(CC(O)=O)C=O PMVGETHEZYTKFP-UHFFFAOYSA-N 0.000 description 2
- CGJJPOYORMGCGE-UHFFFAOYSA-N 3-amino-4-oxobutanoic acid Chemical compound O=CC(N)CC(O)=O CGJJPOYORMGCGE-UHFFFAOYSA-N 0.000 description 2
- OFNISBHGPNMTMS-UHFFFAOYSA-N 3-methylideneoxolane-2,5-dione Chemical compound C=C1CC(=O)OC1=O OFNISBHGPNMTMS-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- ORXXYHCHDWBITL-UHFFFAOYSA-N 4-[(2-ethoxy-5-oxooxolan-3-yl)amino]-4-oxo-2-propan-2-ylbutanoic acid Chemical compound CCOC1OC(=O)CC1NC(=O)CC(C(C)C)C(O)=O ORXXYHCHDWBITL-UHFFFAOYSA-N 0.000 description 2
- UGUBQKZSNQWWEV-UHFFFAOYSA-N 4-oxo-4-phenylmethoxybutanoic acid Chemical compound OC(=O)CCC(=O)OCC1=CC=CC=C1 UGUBQKZSNQWWEV-UHFFFAOYSA-N 0.000 description 2
- KYRBICRKVFJCTO-UHFFFAOYSA-N 4-oxo-5-(2-oxochromen-6-yl)oxy-3-[[4-oxo-4-(3-phenylpropylamino)-2-propan-2-ylbutanoyl]amino]pentanoic acid Chemical compound C=1C=C2OC(=O)C=CC2=CC=1OCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCCC1=CC=CC=C1 KYRBICRKVFJCTO-UHFFFAOYSA-N 0.000 description 2
- SMXYQGVPYWAOQX-UHFFFAOYSA-N 5-bromo-2-[[2-methyl-4-oxo-4-(2-phenylethylamino)butanoyl]amino]-4-oxopentanoic acid Chemical compound BrCC(=O)CC(C(O)=O)NC(=O)C(C)CC(=O)NCCC1=CC=CC=C1 SMXYQGVPYWAOQX-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 102000004091 Caspase-8 Human genes 0.000 description 2
- 108090000538 Caspase-8 Proteins 0.000 description 2
- 102000004039 Caspase-9 Human genes 0.000 description 2
- 108090000566 Caspase-9 Proteins 0.000 description 2
- 108010076667 Caspases Proteins 0.000 description 2
- 102000011727 Caspases Human genes 0.000 description 2
- 102000005927 Cysteine Proteases Human genes 0.000 description 2
- 108010005843 Cysteine Proteases Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241000206672 Gelidium Species 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101000960954 Homo sapiens Interleukin-18 Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000003810 Interleukin-18 Human genes 0.000 description 2
- 108090000171 Interleukin-18 Proteins 0.000 description 2
- 102100039898 Interleukin-18 Human genes 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- SBLUNABTQYDFJM-GMSGAONNSA-N [(1r,4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonamide Chemical compound C1C[C@@]2(CS(N)(=O)=O)C(=O)C[C@@H]1C2(C)C SBLUNABTQYDFJM-GMSGAONNSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- LOXIYOVOOPMAEK-UHFFFAOYSA-N benzyl 5-bromo-4-oxo-3-[[4-oxo-4-(phenylmethoxyamino)-2-propan-2-ylbutanoyl]amino]pentanoate Chemical compound C=1C=CC=CC=1COC(=O)CC(C(=O)CBr)NC(=O)C(C(C)C)CC(=O)NOCC1=CC=CC=C1 LOXIYOVOOPMAEK-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Chemical group 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000019189 interleukin-1 beta production Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 238000005897 peptide coupling reaction Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- ASVONXHWJSSGDF-ROUUACIJSA-N (2s)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-[[(2s)-4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]butanoic acid Chemical compound CC(C)(C)OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)CC(=O)NCCOC1=CC=CC=C1 ASVONXHWJSSGDF-ROUUACIJSA-N 0.000 description 1
- NUXHRVPXEOTAMR-LSLKUGRBSA-N (2s)-4-oxo-3-phenyl-2-propan-2-yl-4-(propylamino)butanoic acid Chemical compound CCCNC(=O)C([C@H](C(C)C)C(O)=O)C1=CC=CC=C1 NUXHRVPXEOTAMR-LSLKUGRBSA-N 0.000 description 1
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000006824 (C1-C6) dialkyl amine group Chemical group 0.000 description 1
- 125000004747 1,1-dimethylethoxycarbonyl group Chemical group CC(C)(OC(=O)*)C 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical class CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- JAGFNESZUUFLPS-HNNXBMFYSA-N 1-o-benzyl 4-o-tert-butyl (2s)-2-propan-2-ylbutanedioate Chemical compound CC(C)(C)OC(=O)C[C@@H](C(C)C)C(=O)OCC1=CC=CC=C1 JAGFNESZUUFLPS-HNNXBMFYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- LXZGUUDIJIOTJB-UHFFFAOYSA-N 2-(benzimidazol-1-yl)ethanamine Chemical compound C1=CC=C2N(CCN)C=NC2=C1 LXZGUUDIJIOTJB-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ITAIPAXSDHHFOF-UHFFFAOYSA-N 2-[[4-oxo-4-(phenylmethoxyamino)-2-propan-2-ylbutanoyl]amino]butanedioic acid Chemical compound OC(=O)CC(C(O)=O)NC(=O)C(C(C)C)CC(=O)NOCC1=CC=CC=C1 ITAIPAXSDHHFOF-UHFFFAOYSA-N 0.000 description 1
- IMLAIXAZMVDRGA-UHFFFAOYSA-N 2-phenoxyethanamine Chemical compound NCCOC1=CC=CC=C1 IMLAIXAZMVDRGA-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- NCAGZEXNEKESQJ-UHFFFAOYSA-N 3-[[2-methyl-4-oxo-4-(2-phenylethylamino)butanoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonyl-(2-phenylethylsulfonyl)amino]-4-oxopentanoic acid Chemical compound C=1C=CC=CC=1CCS(=O)(=O)N(C(=O)OC(C)(C)C)CC(=O)C(CC(O)=O)NC(=O)C(C)CC(=O)NCCC1=CC=CC=C1 NCAGZEXNEKESQJ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ISULZYQDGYXDFW-UHFFFAOYSA-N 3-methylbutanoyl chloride Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 1
- LYUQWQRTDLVQGA-UHFFFAOYSA-N 3-phenylpropylamine Chemical compound NCCCC1=CC=CC=C1 LYUQWQRTDLVQGA-UHFFFAOYSA-N 0.000 description 1
- ASVONXHWJSSGDF-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]butanoic acid Chemical compound CC(C)(C)OC(=O)CC(C(O)=O)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 ASVONXHWJSSGDF-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- JJIHGWDABPZPQT-UHFFFAOYSA-N 4-o-tert-butyl 1-o-methyl 2-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]butanedioate Chemical compound CC(C)(C)OC(=O)CC(C(=O)OC)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 JJIHGWDABPZPQT-UHFFFAOYSA-N 0.000 description 1
- JPOOCZBMQLFBIZ-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)butanoic acid Chemical compound OC(=O)CC(C=O)NC(=O)OCC1=CC=CC=C1 JPOOCZBMQLFBIZ-UHFFFAOYSA-N 0.000 description 1
- VLNYIOYVRRRCER-UHFFFAOYSA-N 5-[3-(1h-imidazol-2-yl)naphthalen-2-yl]oxy-4-oxo-3-[[4-oxo-4-(3-phenylpropylamino)-2-propan-2-ylbutanoyl]amino]pentanoic acid Chemical compound C=1C2=CC=CC=C2C=C(C=2NC=CN=2)C=1OCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)CC(=O)NCCCC1=CC=CC=C1 VLNYIOYVRRRCER-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101150047706 CASP6 gene Proteins 0.000 description 1
- LBPWOOAFXLMXBR-UHFFFAOYSA-N CC(CC(=O)NCCC1=CC=CC=C1)C(=O)NC(CC(=O)O)C(=O)OC Chemical compound CC(CC(=O)NCCC1=CC=CC=C1)C(=O)NC(CC(=O)O)C(=O)OC LBPWOOAFXLMXBR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000004018 Caspase 6 Human genes 0.000 description 1
- 108090000425 Caspase 6 Proteins 0.000 description 1
- 108090000567 Caspase 7 Proteins 0.000 description 1
- 102100035904 Caspase-1 Human genes 0.000 description 1
- 102000004068 Caspase-10 Human genes 0.000 description 1
- 108090000572 Caspase-10 Proteins 0.000 description 1
- 102000004046 Caspase-2 Human genes 0.000 description 1
- 108090000552 Caspase-2 Proteins 0.000 description 1
- 102100025597 Caspase-4 Human genes 0.000 description 1
- 101710090338 Caspase-4 Proteins 0.000 description 1
- 102100038916 Caspase-5 Human genes 0.000 description 1
- 101710090333 Caspase-5 Proteins 0.000 description 1
- 102100038902 Caspase-7 Human genes 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 101000793880 Homo sapiens Caspase-3 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 1
- 241000476982 Yania Species 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- PWQLZSHJRGGLBC-UHFFFAOYSA-N acetonitrile;carbon dioxide Chemical compound CC#N.O=C=O PWQLZSHJRGGLBC-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- PMLJIHNCYNOQEQ-UHFFFAOYSA-N aspartic 1-amide Chemical compound NC(=O)C(N)CC(O)=O PMLJIHNCYNOQEQ-UHFFFAOYSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- JUYJICAKWGYMKU-FQEVSTJZSA-N benzyl (2s)-4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoate Chemical compound C([C@@H](C(C)C)C(=O)OCC=1C=CC=CC=1)C(=O)NCCOC1=CC=CC=C1 JUYJICAKWGYMKU-FQEVSTJZSA-N 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- CFBGXYDUODCMNS-UHFFFAOYSA-N cyclobutene Chemical compound C1CC=C1 CFBGXYDUODCMNS-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentenylidene Natural products C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- BQAMWLOABQRMAO-INIZCTEOSA-N dibenzyl (2s)-2-aminobutanedioate Chemical compound C([C@H](N)C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 BQAMWLOABQRMAO-INIZCTEOSA-N 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- NBJMJWGVQKYABP-UHFFFAOYSA-N ethyl 3,4-diamino-4-oxobutanoate Chemical compound CCOC(=O)CC(N)C(N)=O NBJMJWGVQKYABP-UHFFFAOYSA-N 0.000 description 1
- GZQPVGVPROVQSG-UHFFFAOYSA-N ethyl 4-amino-4-oxo-3-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]butanoate Chemical compound CCOC(=O)CC(C(N)=O)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 GZQPVGVPROVQSG-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 231100000318 excitotoxic Toxicity 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 230000027950 fever generation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 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 description 1
- 239000003906 humectant Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- 230000014828 interferon-gamma production Effects 0.000 description 1
- 108010052790 interleukin 1 precursor Proteins 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- 229910052740 iodine Chemical group 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- AHCNXVCAVUYIOU-UHFFFAOYSA-M lithium hydroperoxide Chemical compound [Li+].[O-]O AHCNXVCAVUYIOU-UHFFFAOYSA-M 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- VBEGHXKAFSLLGE-UHFFFAOYSA-N n-phenylnitramide Chemical compound [O-][N+](=O)NC1=CC=CC=C1 VBEGHXKAFSLLGE-UHFFFAOYSA-N 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
- 239000000668 oral spray Substances 0.000 description 1
- 229940041678 oral spray Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- BRILIRGTZOKLTC-PMACEKPBSA-N tert-butyl (3s)-4-oxo-3-[[(2s)-4-oxo-4-(3-phenylpropylamino)-2-propan-2-ylbutanoyl]amino]butanoate Chemical compound CC(C)(C)OC(=O)C[C@@H](C=O)NC(=O)[C@H](C(C)C)CC(=O)NCCCC1=CC=CC=C1 BRILIRGTZOKLTC-PMACEKPBSA-N 0.000 description 1
- XLIOETXUAMCVMT-UHFFFAOYSA-N tert-butyl 3-[[5-[(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methylsulfonyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-1,4-dioxo-1-phenylmethoxypentan-3-yl]carbamoyl]-4-methylpentanoate Chemical compound C1CC(C2(C)C)CC(=O)C12CS(=O)(=O)N(C(=O)OC(C)(C)C)CC(=O)C(NC(=O)C(CC(=O)OC(C)(C)C)C(C)C)CC(=O)OCC1=CC=CC=C1 XLIOETXUAMCVMT-UHFFFAOYSA-N 0.000 description 1
- UQJFHJXKKCTGDZ-UHFFFAOYSA-N tert-butyl 3-cyano-3-[[4-oxo-4-(2-phenoxyethylamino)-2-propan-2-ylbutanoyl]amino]propanoate Chemical compound CC(C)(C)OC(=O)CC(C#N)NC(=O)C(C(C)C)CC(=O)NCCOC1=CC=CC=C1 UQJFHJXKKCTGDZ-UHFFFAOYSA-N 0.000 description 1
- BGXVADAFIXBNPZ-UHFFFAOYSA-N tert-butyl n-(2-phenylethylsulfonyl)carbamate Chemical compound CC(C)(C)OC(=O)NS(=O)(=O)CCC1=CC=CC=C1 BGXVADAFIXBNPZ-UHFFFAOYSA-N 0.000 description 1
- CQFGEVCKRNWSAH-GENIYJEYSA-N tert-butyl-[[(1S)-7,7-dimethyl-2-oxo-1-bicyclo[2.2.1]heptanyl]methylsulfonyl]carbamic acid Chemical compound C1CC2CC(=O)[C@@]1(CS(=O)(=O)N(C(O)=O)C(C)(C)C)C2(C)C CQFGEVCKRNWSAH-GENIYJEYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
- C07C255/29—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups and acylated amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/10—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D249/18—Benzotriazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/14—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 6 and unsubstituted in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Furan Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US8432098P | 1998-05-05 | 1998-05-05 | |
PCT/US1999/009463 WO1999056765A1 (en) | 1998-05-05 | 1999-04-30 | SUCCINAMIDE INHIBITORS OF INTERLEUKIN-1β CONVERTING ENZYME |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20000744A2 true HRP20000744A2 (en) | 2001-06-30 |
Family
ID=22184211
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20000744A HRP20000744A2 (en) | 1998-05-05 | 2000-11-03 | Succinamide inhibitors of interleukin-1beta converting enzyme |
Country Status (27)
Country | Link |
---|---|
EP (1) | EP1082127B1 (pt) |
JP (1) | JP2002513766A (pt) |
KR (1) | KR20010052307A (pt) |
CN (1) | CN1308542A (pt) |
AP (1) | AP2000001992A0 (pt) |
AT (1) | ATE298242T1 (pt) |
AU (1) | AU758120B2 (pt) |
BG (1) | BG105002A (pt) |
BR (1) | BR9911010A (pt) |
CA (1) | CA2327507A1 (pt) |
DE (1) | DE69925914T2 (pt) |
EA (1) | EA200001152A1 (pt) |
EE (1) | EE200000644A (pt) |
ES (1) | ES2242394T3 (pt) |
HR (1) | HRP20000744A2 (pt) |
HU (1) | HUP0101963A3 (pt) |
ID (1) | ID30124A (pt) |
IL (1) | IL139416A0 (pt) |
IS (1) | IS5674A (pt) |
NO (1) | NO20005537L (pt) |
OA (1) | OA11550A (pt) |
PL (1) | PL343837A1 (pt) |
SK (1) | SK16732000A3 (pt) |
TR (1) | TR200003252T2 (pt) |
WO (1) | WO1999056765A1 (pt) |
YU (1) | YU67900A (pt) |
ZA (1) | ZA200006881B (pt) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002538151A (ja) | 1999-03-02 | 2002-11-12 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | カテプシンの可逆的インヒビターとして有用な化合物 |
DE60035037T2 (de) | 1999-04-09 | 2008-01-31 | Cytovia, Inc., San Diego | Caspase inhibitoren und ihre verwendung |
WO2001009110A1 (en) * | 1999-07-30 | 2001-02-08 | Boehringer Ingelheim Pharmaceuticals, Inc. | Novel succinate derivative compounds useful as cysteine protease inhibitors |
BR0013666A (pt) | 1999-08-27 | 2002-05-14 | Cytovia Inc | "alfa"-hidróxi-ácidos substituìdos inibidores de caspases e o seu uso |
US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
US20020052323A1 (en) * | 2000-08-30 | 2002-05-02 | Jinhai Wang | Quinoline-(C=O)-(multiple amino acids)-leaving group compounds for pharmaceutical compositions and reagents |
CA2447999C (en) * | 2001-05-23 | 2011-04-26 | Vertex Pharmaceuticals Incorporated | Caspase inhibitors and uses thereof |
CA2463770A1 (en) | 2001-10-29 | 2003-05-08 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as reversible inhibitors of cysteine proteases |
US7115654B2 (en) | 2002-06-05 | 2006-10-03 | Sunesis Pharmaceuticals, Inc. | Caspase-1 inhibitors and methods for their use |
US7297714B2 (en) * | 2003-10-21 | 2007-11-20 | Irm Llc | Inhibitors of cathepsin S |
AU2005249503B2 (en) | 2003-11-10 | 2011-08-25 | Vertex Pharmaceuticals Incorporated | ICE inhibitors for the treatment of autoinflammatory diseases |
ZA200610133B (en) | 2004-05-15 | 2008-05-28 | Vertex Pharma | Treating seizures using ice inhibitors |
WO2007115231A2 (en) * | 2006-03-30 | 2007-10-11 | Chemocentryx, Inc. | Cxcr4 modulators |
US7671069B2 (en) | 2006-03-30 | 2010-03-02 | Chemocentryx, Inc. | Tricyclic, heteroaromatic compounds modulating CXCR4 and/ or CXCR7 |
US9365612B2 (en) | 2010-01-29 | 2016-06-14 | United States Of America As Represented By The Secretary, Department Of Health And Human Services | Caspase inhibitors |
JP6006908B2 (ja) | 2010-11-05 | 2016-10-12 | ブランダイス ユニバーシティBrandeis University | Ice阻害化合物およびその使用 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW394760B (en) * | 1993-09-07 | 2000-06-21 | Hoffmann La Roche | Novel Carboxamides, process for their preparation and pharmaceutical composition containing the same |
-
1999
- 1999-04-30 CN CN99808265A patent/CN1308542A/zh active Pending
- 1999-04-30 WO PCT/US1999/009463 patent/WO1999056765A1/en active IP Right Grant
- 1999-04-30 IL IL13941699A patent/IL139416A0/xx unknown
- 1999-04-30 EA EA200001152A patent/EA200001152A1/ru unknown
- 1999-04-30 KR KR1020007012300A patent/KR20010052307A/ko not_active Application Discontinuation
- 1999-04-30 YU YU67900A patent/YU67900A/sh unknown
- 1999-04-30 PL PL99343837A patent/PL343837A1/xx not_active Application Discontinuation
- 1999-04-30 JP JP2000546789A patent/JP2002513766A/ja active Pending
- 1999-04-30 ID IDW20002501A patent/ID30124A/id unknown
- 1999-04-30 ES ES99918930T patent/ES2242394T3/es not_active Expired - Lifetime
- 1999-04-30 CA CA002327507A patent/CA2327507A1/en not_active Abandoned
- 1999-04-30 TR TR2000/03252T patent/TR200003252T2/xx unknown
- 1999-04-30 BR BR9911010-5A patent/BR9911010A/pt not_active IP Right Cessation
- 1999-04-30 AT AT99918930T patent/ATE298242T1/de not_active IP Right Cessation
- 1999-04-30 EP EP99918930A patent/EP1082127B1/en not_active Expired - Lifetime
- 1999-04-30 AP APAP/P/2000/001992A patent/AP2000001992A0/en unknown
- 1999-04-30 DE DE69925914T patent/DE69925914T2/de not_active Expired - Fee Related
- 1999-04-30 EE EEP200000644A patent/EE200000644A/xx unknown
- 1999-04-30 SK SK1673-2000A patent/SK16732000A3/sk unknown
- 1999-04-30 AU AU36730/99A patent/AU758120B2/en not_active Ceased
- 1999-04-30 HU HU0101963A patent/HUP0101963A3/hu unknown
- 1999-04-30 OA OA1200000305A patent/OA11550A/en unknown
-
2000
- 2000-10-20 IS IS5674A patent/IS5674A/is unknown
- 2000-11-02 NO NO20005537A patent/NO20005537L/no not_active Application Discontinuation
- 2000-11-03 HR HR20000744A patent/HRP20000744A2/hr not_active Application Discontinuation
- 2000-11-23 ZA ZA200006881A patent/ZA200006881B/en unknown
- 2000-11-29 BG BG105002A patent/BG105002A/bg unknown
Also Published As
Publication number | Publication date |
---|---|
ID30124A (id) | 2001-11-08 |
EP1082127A1 (en) | 2001-03-14 |
EP1082127A4 (en) | 2002-10-09 |
AU758120B2 (en) | 2003-03-13 |
HUP0101963A3 (en) | 2003-07-28 |
PL343837A1 (en) | 2001-09-10 |
NO20005537L (no) | 2000-12-20 |
EA200001152A1 (ru) | 2001-06-25 |
EP1082127B1 (en) | 2005-06-22 |
DE69925914D1 (de) | 2005-07-28 |
BG105002A (bg) | 2001-07-31 |
SK16732000A3 (sk) | 2001-06-11 |
AU3673099A (en) | 1999-11-23 |
IS5674A (is) | 2000-10-20 |
HUP0101963A2 (hu) | 2001-10-28 |
BR9911010A (pt) | 2005-12-06 |
CA2327507A1 (en) | 1999-11-11 |
AP2000001992A0 (en) | 2000-12-31 |
EE200000644A (et) | 2002-04-15 |
YU67900A (sh) | 2002-12-10 |
DE69925914T2 (de) | 2006-05-11 |
KR20010052307A (ko) | 2001-06-25 |
NO20005537D0 (no) | 2000-11-02 |
TR200003252T2 (tr) | 2001-04-20 |
IL139416A0 (en) | 2001-11-25 |
WO1999056765A1 (en) | 1999-11-11 |
JP2002513766A (ja) | 2002-05-14 |
ES2242394T3 (es) | 2005-11-01 |
OA11550A (en) | 2004-06-04 |
ATE298242T1 (de) | 2005-07-15 |
CN1308542A (zh) | 2001-08-15 |
ZA200006881B (en) | 2002-05-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20000744A2 (en) | Succinamide inhibitors of interleukin-1beta converting enzyme | |
AU738341B2 (en) | Asparate ester inhibitors of interleukin-1beta converting enzyme | |
JP4676676B2 (ja) | カスパーゼ阻害剤としての複素環ジカルバミド | |
US5922770A (en) | Compounds with growth hormone releasing properties | |
AU722936B2 (en) | Inhibitors of interleukin-1beta converting enzyme | |
JP2008285493A (ja) | インターロイキン−1β変換酵素のインヒビター | |
SK67394A3 (en) | Alpha (-heteroaryloxymethylketones,pharmaceutical agents with their contents and using of these ketones or pharmaceutical agent for production of medicine | |
JP2002509153A (ja) | インターロイキン−1β変換酵素(ICE)のインビボ阻害剤としてのN−[2−(5−ベンジルオキシカルボニル−アミノ−6−オキソ−2−(4−フルオロフェニル)−1,6−ジヒドロ−1−ピリミジニル)アセトキシル]−L−アスパラギン酸アルデヒド | |
JP2001508404A (ja) | スルホンアミドインターロイキン―1β変換酵素阻害剤 | |
EP1157998B1 (en) | Heterocyclic compounds, intermediates thereof and elastase inhibitors | |
US20230250067A1 (en) | Caspase inhibitors and methods of use thereof | |
US5166154A (en) | Imidazo[1,2-a]piperazines | |
MXPA00010886A (en) | SUCCINAMIDE INHIBITORS OF INTERLEUKIN-1&bgr;CONVERTING ENZYME | |
CZ20004084A3 (cs) | Sukcinamidové inhibitory konverzního enzymu interleukinu-lbeta | |
JP2002138048A (ja) | 複素環式化合物からなる医薬 | |
MXPA00004970A (en) | N-[2-(5-benzyloxycarbonyl-amino-6-oxo-2-(4- fluorophenyl)-1,6-dihydro -1-pyrimidinyl)aceto- xyl]-l-aspartic acid aldehyde as an i(in vivo) inhibitor of interleukin-1b converting enzyme (ice) | |
DE3932817A1 (de) | Renin-hemmende aminooligohydroxy-derivate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A1OB | Publication of a patent application | ||
ARAI | Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application | ||
ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20020430 Year of fee payment: 4 |
|
OBST | Application withdrawn |