JP2002532490A - 4−および5−アルキニルオキシンドールと4−および5−アルケニルオキシンドール - Google Patents
4−および5−アルキニルオキシンドールと4−および5−アルケニルオキシンドールInfo
- Publication number
- JP2002532490A JP2002532490A JP2000588166A JP2000588166A JP2002532490A JP 2002532490 A JP2002532490 A JP 2002532490A JP 2000588166 A JP2000588166 A JP 2000588166A JP 2000588166 A JP2000588166 A JP 2000588166A JP 2002532490 A JP2002532490 A JP 2002532490A
- Authority
- JP
- Japan
- Prior art keywords
- dihydro
- methylene
- pyrrol
- indol
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 151
- -1 (R) rac- (Z) -1,3-dihydro-4- [3-hydroxy-3- (4-phenoxyphenyl) -1-propynyl] -3- [ (3-methoxy-1H-pyrrol-2-yl) methylene] -2H-indol-2-one Chemical compound 0.000 claims description 124
- 150000001875 compounds Chemical class 0.000 claims description 112
- 230000015572 biosynthetic process Effects 0.000 claims description 89
- 238000003786 synthesis reaction Methods 0.000 claims description 89
- 125000000623 heterocyclic group Chemical group 0.000 claims description 88
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 83
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 claims description 59
- 239000000203 mixture Substances 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 47
- 150000002367 halogens Chemical class 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- YLQAQZFUXVPZGQ-LCYFTJDESA-N (3z)-5-ethynyl-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C#C)C=C2\C1=C\C1=CC=CN1 YLQAQZFUXVPZGQ-LCYFTJDESA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 12
- 239000000651 prodrug Substances 0.000 claims description 11
- 229940002612 prodrug Drugs 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
- 208000027866 inflammatory disease Diseases 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- SENKVSSHGZDFNW-LGMDPLHJSA-N (3z)-4-[3-hydroxy-3-(3-nitrophenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(C=CC=4)[N+]([O-])=O)C=CC=C3NC\2=O)=C1OC SENKVSSHGZDFNW-LGMDPLHJSA-N 0.000 claims description 6
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 6
- FLUWNHUCLAWPKG-ATVHPVEESA-N (3z)-4-[3-hydroxy-3-(2,4,5-trimethoxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C(=CC(OC)=C(OC)C=4)OC)C=CC=C3NC\2=O)=C1OC FLUWNHUCLAWPKG-ATVHPVEESA-N 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- 239000002207 metabolite Substances 0.000 claims description 5
- LLTZGYZYWGAACV-HKVBYMSFSA-N (3z)-1-[(e)-2-phenylethenyl]-3-(1h-pyrrol-2-ylmethylidene)indol-2-one Chemical compound C12=CC=CC=C2\C(=C\C=2NC=CC=2)C(=O)N1\C=C\C1=CC=CC=C1 LLTZGYZYWGAACV-HKVBYMSFSA-N 0.000 claims description 4
- MUMWQVXWSSNTMM-PTNGSMBKSA-N (3z)-4-(3-hydroxy-3-thiophen-3-ylprop-1-ynyl)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C4=CSC=C4)C=CC=C3NC\2=O)=C1OC MUMWQVXWSSNTMM-PTNGSMBKSA-N 0.000 claims description 4
- YJCIDAJKFWKYCS-OWBHPGMISA-N (3z)-4-[3-hydroxy-3-(3-methoxythiophen-2-yl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C4=C(C=CS4)OC)C=CC=C3NC\2=O)=C1OC YJCIDAJKFWKYCS-OWBHPGMISA-N 0.000 claims description 4
- FAFVKKUTZMVGHK-JXAWBTAJSA-N methyl 2-[4-[1-hydroxy-3-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]-2-methoxyphenoxy]acetate Chemical compound C1=C(OC)C(OCC(=O)OC)=CC=C1C(O)C#CC1=CC=CC(NC\2=O)=C1C/2=C/C1=C(OC)C=CN1 FAFVKKUTZMVGHK-JXAWBTAJSA-N 0.000 claims description 4
- DKNKBLBPQHSVGJ-HKWRFOASSA-N n-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-4-(2-pyridin-3-ylethynyl)-1h-indol-5-yl]-2-thiophen-2-ylacetamide Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=NC=CC=4)C(NC(=O)CC=4SC=CC=4)=CC=C3NC\2=O)=C1OC DKNKBLBPQHSVGJ-HKWRFOASSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- ZTAYJHNUGMKDAC-TVYBWHDCSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1-[(e)-2-phenylethenyl]indol-2-one Chemical compound C1=CNC(\C=C/2C3=CC=CC=C3N(\C=C\C=3C=CC=CC=3)C\2=O)=C1OC ZTAYJHNUGMKDAC-TVYBWHDCSA-N 0.000 claims description 3
- LFSKVYQOHAAGQB-VKAVYKQESA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(2-phenylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=CC=CC=4)C=CC=C3NC\2=O)=C1OC LFSKVYQOHAAGQB-VKAVYKQESA-N 0.000 claims description 3
- LBRHIACYAJUKFX-VBKFSLOCSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(2-pyridin-3-ylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=NC=CC=4)C=CC=C3NC\2=O)=C1OC LBRHIACYAJUKFX-VBKFSLOCSA-N 0.000 claims description 3
- HHYIPICNMBTBHU-PTNGSMBKSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-5-nitro-4-(2-pyridin-3-ylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=NC=CC=4)C(=CC=C3NC\2=O)[N+]([O-])=O)=C1OC HHYIPICNMBTBHU-PTNGSMBKSA-N 0.000 claims description 3
- PXCCQARRVLKNIM-SQFISAMPSA-N (3z)-4-(3-hydroxy-3-pyridin-2-ylprop-1-ynyl)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4N=CC=CC=4)C=CC=C3NC\2=O)=C1OC PXCCQARRVLKNIM-SQFISAMPSA-N 0.000 claims description 3
- GIGNTIVPOROLOI-VBKFSLOCSA-N (3z)-4-(3-hydroxy-3-pyridin-3-ylprop-1-ynyl)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=NC=CC=4)C=CC=C3NC\2=O)=C1OC GIGNTIVPOROLOI-VBKFSLOCSA-N 0.000 claims description 3
- RGVWLPQHWJEXQI-OWBHPGMISA-N (3z)-4-(3-hydroxy-3-thiophen-2-ylprop-1-ynyl)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4SC=CC=4)C=CC=C3NC\2=O)=C1OC RGVWLPQHWJEXQI-OWBHPGMISA-N 0.000 claims description 3
- JIZBUYBBALMSAD-OWBHPGMISA-N (3z)-4-[3-(furan-2-yl)-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4OC=CC=4)C=CC=C3NC\2=O)=C1OC JIZBUYBBALMSAD-OWBHPGMISA-N 0.000 claims description 3
- RRCHGUVCSGQAPF-LGMDPLHJSA-N (3z)-4-[3-hydroxy-3-(4-hydroxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(O)=CC=4)C=CC=C3NC\2=O)=C1OC RRCHGUVCSGQAPF-LGMDPLHJSA-N 0.000 claims description 3
- RSYGPYSNRUOCKK-JXAWBTAJSA-N (3z)-4-[3-hydroxy-3-(4-methoxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(OC)=CC=4)C=CC=C3NC\2=O)=C1OC RSYGPYSNRUOCKK-JXAWBTAJSA-N 0.000 claims description 3
- NSIKGWYDIJARHZ-VBKFSLOCSA-N (3z)-4-[3-hydroxy-3-(7-methoxy-1,3-benzodioxol-5-yl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C=5OCOC=5C=4)C=CC=C3NC\2=O)=C1OC NSIKGWYDIJARHZ-VBKFSLOCSA-N 0.000 claims description 3
- GHRIUISNTDKVTN-QOCHGBHMSA-N (3z)-4-[3-hydroxy-3-[3-methoxy-4-(2-morpholin-4-ylethoxy)phenyl]prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C(OCCN5CCOCC5)=CC=4)C=CC=C3NC\2=O)=C1OC GHRIUISNTDKVTN-QOCHGBHMSA-N 0.000 claims description 3
- BZTQDBKGIBAREQ-NMWGTECJSA-N (3z)-4-[3-hydroxy-3-[4-(2-morpholin-4-ylethoxy)phenyl]prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(OCCN5CCOCC5)=CC=4)C=CC=C3NC\2=O)=C1OC BZTQDBKGIBAREQ-NMWGTECJSA-N 0.000 claims description 3
- DTBCCPGQXHCCJH-RGEXLXHISA-N (3z)-5-(2-phenylethynyl)-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C#CC=3C=CC=CC=3)C=C2\C1=C\C1=CC=CN1 DTBCCPGQXHCCJH-RGEXLXHISA-N 0.000 claims description 3
- ZSXMOOAYMVIBSX-AQTBWJFISA-N (3z)-5-[2-(2-nitrophenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C#CC1=CC=C(NC(=O)\C2=C/C=3NC=CC=3)C2=C1 ZSXMOOAYMVIBSX-AQTBWJFISA-N 0.000 claims description 3
- YRAQZUQALGLTGH-UYRXBGFRSA-N (3z)-5-[2-(4-nitrophenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1C#CC1=CC=C(NC(=O)\C2=C/C=3NC=CC=3)C2=C1 YRAQZUQALGLTGH-UYRXBGFRSA-N 0.000 claims description 3
- YHIFTRRHGPGDKD-PTNGSMBKSA-N (3z)-5-amino-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(2-pyridin-3-ylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=NC=CC=4)C(N)=CC=C3NC\2=O)=C1OC YHIFTRRHGPGDKD-PTNGSMBKSA-N 0.000 claims description 3
- GZSXMGUALNRWHL-XFXZXTDPSA-N (3z)-5-ethynyl-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=CC(=CC=C3NC\2=O)C#C)=C1OC GZSXMGUALNRWHL-XFXZXTDPSA-N 0.000 claims description 3
- RSEGQJSFDGPSHB-LGMDPLHJSA-N 2-[4-[1-hydroxy-3-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]-2-methoxyphenoxy]acetic acid Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C(OCC(O)=O)=CC=4)C=CC=C3NC\2=O)=C1OC RSEGQJSFDGPSHB-LGMDPLHJSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- BXIUQXIGICXFHK-UYRXBGFRSA-N (3Z)-1-ethynyl-5-(4-hydroxyphenyl)-3-(1H-pyrrol-2-ylmethylidene)indol-2-one Chemical compound OC1=CC=C(C=C1)C=1C=C2/C(/C(N(C2=CC1)C#C)=O)=C/C=1NC=CC1 BXIUQXIGICXFHK-UYRXBGFRSA-N 0.000 claims description 2
- SOYFKPDKCDIHMW-SSZFMOIBSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(2-pyridin-4-ylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=CN=CC=4)C=CC=C3NC\2=O)=C1OC SOYFKPDKCDIHMW-SSZFMOIBSA-N 0.000 claims description 2
- CIBQBCXWQYRSFJ-SDXDJHTJSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(3-phenoxyprop-1-ynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CCOC=4C=CC=CC=4)C=CC=C3NC\2=O)=C1OC CIBQBCXWQYRSFJ-SDXDJHTJSA-N 0.000 claims description 2
- IZXHJFBVDXOSDL-VKAVYKQESA-N (3z)-4-(3-hydroxy-3-phenylprop-1-ynyl)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC=CC=4)C=CC=C3NC\2=O)=C1OC IZXHJFBVDXOSDL-VKAVYKQESA-N 0.000 claims description 2
- YYQIGYCJNSROAA-IUWFAXKNSA-N (3z)-4-[(e)-2-(3,4-dimethoxyphenyl)ethenyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(\C=C\C=4C=C(OC)C(OC)=CC=4)C=CC=C3NC\2=O)=C1OC YYQIGYCJNSROAA-IUWFAXKNSA-N 0.000 claims description 2
- DTCDOONGFRBLDF-PAAQWSFZSA-N (3z)-4-[(e)-2-(4-methoxyphenyl)ethenyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(\C=C\C=4C=CC(OC)=CC=4)C=CC=C3NC\2=O)=C1OC DTCDOONGFRBLDF-PAAQWSFZSA-N 0.000 claims description 2
- COGFBJXZPOJDJS-JXAWBTAJSA-N (3z)-4-[2-(4-methoxyphenyl)ethynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=CC(OC)=CC=4)C=CC=C3NC\2=O)=C1OC COGFBJXZPOJDJS-JXAWBTAJSA-N 0.000 claims description 2
- NUCZORXTPQUVGZ-VBKFSLOCSA-N (3z)-4-[3-(1,3-benzodioxol-5-yl)-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C5OCOC5=CC=4)C=CC=C3NC\2=O)=C1OC NUCZORXTPQUVGZ-VBKFSLOCSA-N 0.000 claims description 2
- WNSGLFJZOFFYTE-LGMDPLHJSA-N (3z)-4-[3-(3-aminophenyl)-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(N)C=CC=4)C=CC=C3NC\2=O)=C1OC WNSGLFJZOFFYTE-LGMDPLHJSA-N 0.000 claims description 2
- WXWYYUPZZCUBKY-PYCFMQQDSA-N (3z)-4-[3-[4-[3-(dimethylamino)propoxy]phenyl]-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(OCCCN(C)C)=CC=4)C=CC=C3NC\2=O)=C1OC WXWYYUPZZCUBKY-PYCFMQQDSA-N 0.000 claims description 2
- FGWZGTXNTSYELB-VKAVYKQESA-N (3z)-4-[3-hydroxy-3-(2-methoxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C(=CC=CC=4)OC)C=CC=C3NC\2=O)=C1OC FGWZGTXNTSYELB-VKAVYKQESA-N 0.000 claims description 2
- YXGSOBZQGVSTRQ-JXAWBTAJSA-N (3z)-4-[3-hydroxy-3-(3-methoxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C=CC=4)C=CC=C3NC\2=O)=C1OC YXGSOBZQGVSTRQ-JXAWBTAJSA-N 0.000 claims description 2
- ARAMICXSYSETIU-SSZFMOIBSA-N (3z)-4-[3-hydroxy-3-(4-hydroxy-3-methoxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C(O)=CC=4)C=CC=C3NC\2=O)=C1OC ARAMICXSYSETIU-SSZFMOIBSA-N 0.000 claims description 2
- BGMXWZJIMIWZLP-UYRXBGFRSA-N (3z)-5-[2-(3-nitrophenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound [O-][N+](=O)C1=CC=CC(C#CC=2C=C3C(=C/C=4NC=CC=4)/C(=O)NC3=CC=2)=C1 BGMXWZJIMIWZLP-UYRXBGFRSA-N 0.000 claims description 2
- SUIUQQPGKUZEOX-ZHZULCJRSA-N (3z)-5-[2-(4-methoxyphenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=CC(OC)=CC=C1C#CC1=CC=C(NC(=O)\C2=C/C=3NC=CC=3)C2=C1 SUIUQQPGKUZEOX-ZHZULCJRSA-N 0.000 claims description 2
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 2
- HSZQLJPSDFRYJD-LGMDPLHJSA-N 4-[1-hydroxy-3-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]benzoic acid Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(=CC=4)C(O)=O)C=CC=C3NC\2=O)=C1OC HSZQLJPSDFRYJD-LGMDPLHJSA-N 0.000 claims description 2
- 102100039250 Essential MCU regulator, mitochondrial Human genes 0.000 claims description 2
- 101000813097 Homo sapiens Essential MCU regulator, mitochondrial Proteins 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000004965 chloroalkyl group Chemical group 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- RZTFYTLJOXSQKQ-PAAQWSFZSA-N methyl 4-[(e)-2-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]ethenyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1\C=C\C1=CC=CC(NC\2=O)=C1C/2=C/C1=C(OC)C=CN1 RZTFYTLJOXSQKQ-PAAQWSFZSA-N 0.000 claims description 2
- WNPUJTJJHQVVHZ-RGEXLXHISA-N n-[4-[1-hydroxy-3-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]phenyl]acetamide Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(NC(C)=O)=CC=4)C=CC=C3NC\2=O)=C1OC WNPUJTJJHQVVHZ-RGEXLXHISA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 5
- SOQYSQMXYLSISO-SSZFMOIBSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(2-pyridin-2-ylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4N=CC=CC=4)C=CC=C3NC\2=O)=C1OC SOQYSQMXYLSISO-SSZFMOIBSA-N 0.000 claims 2
- OYQFBEWTCTWNGC-VKAVYKQESA-N (3z)-4-[3-(2,3-dimethoxyphenyl)-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C(=C(OC)C=CC=4)OC)C=CC=C3NC\2=O)=C1OC OYQFBEWTCTWNGC-VKAVYKQESA-N 0.000 claims 2
- QOXYBCGXASWZIY-VKAVYKQESA-N (3z)-4-[3-(3,4-dimethoxyphenyl)-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C(OC)=CC=4)C=CC=C3NC\2=O)=C1OC QOXYBCGXASWZIY-VKAVYKQESA-N 0.000 claims 2
- PBNDYRBZMZOPIF-OWBHPGMISA-N (3z)-4-[3-hydroxy-3-(1h-pyrrol-2-yl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4NC=CC=4)C=CC=C3NC\2=O)=C1OC PBNDYRBZMZOPIF-OWBHPGMISA-N 0.000 claims 2
- QOZJTHXUJVMUTK-SSZFMOIBSA-N (3z)-4-[3-hydroxy-3-(3-hydroxy-4-methoxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(O)C(OC)=CC=4)C=CC=C3NC\2=O)=C1OC QOZJTHXUJVMUTK-SSZFMOIBSA-N 0.000 claims 2
- PTXMJHSJWXPRSV-UHFFFAOYSA-N N1C(=CC=C1)C=C1/C(N(C2=CC=C(C=C12)C=1SC=CC1)C#C)=O Chemical compound N1C(=CC=C1)C=C1/C(N(C2=CC=C(C=C12)C=1SC=CC1)C#C)=O PTXMJHSJWXPRSV-UHFFFAOYSA-N 0.000 claims 2
- PVZQFACHIBRALC-UYRXBGFRSA-N (3Z)-1-ethynyl-5-(3-hydroxyphenyl)-3-(1H-pyrrol-2-ylmethylidene)indol-2-one Chemical compound OC=1C=C(C=CC1)C=1C=C2/C(/C(N(C2=CC1)C#C)=O)=C/C=1NC=CC1 PVZQFACHIBRALC-UYRXBGFRSA-N 0.000 claims 1
- RNBIKCQNFKTTBX-PDGQHHTCSA-N (3Z)-1-ethynyl-5-pyridin-3-yl-3-(1H-pyrrol-2-ylmethylidene)indol-2-one Chemical compound N1=CC(=CC=C1)C=1C=C2/C(/C(N(C2=CC1)C#C)=O)=C/C=1NC=CC1 RNBIKCQNFKTTBX-PDGQHHTCSA-N 0.000 claims 1
- WPAMZQZOUUBLDX-HNMBUVAWSA-N (3z)-4-[(e)-2-(2-chlorophenyl)ethenyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound ClC1=CC=CC=C1\C=C\C1=CC=CC(NC\2=O)=C1C/2=C/C1=CC=CN1 WPAMZQZOUUBLDX-HNMBUVAWSA-N 0.000 claims 1
- QZEXZSLTGGACSR-CYVLTUHYSA-N (3z)-4-[3-[4-(dimethylamino)phenyl]-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(=CC=4)N(C)C)C=CC=C3NC\2=O)=C1OC QZEXZSLTGGACSR-CYVLTUHYSA-N 0.000 claims 1
- JCNUEOJEPMPPIV-LGMDPLHJSA-N (3z)-4-[3-hydroxy-3-(3-hydroxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(O)C=CC=4)C=CC=C3NC\2=O)=C1OC JCNUEOJEPMPPIV-LGMDPLHJSA-N 0.000 claims 1
- HEBQMEDMHXTFPG-AQTBWJFISA-N (3z)-5-(2-pyridin-2-ylethynyl)-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C#CC=3N=CC=CC=3)C=C2\C1=C\C1=CC=CN1 HEBQMEDMHXTFPG-AQTBWJFISA-N 0.000 claims 1
- FIXDPUBAPHNBIB-UYRXBGFRSA-N (3z)-5-[2-(4-aminophenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=CC(N)=CC=C1C#CC1=CC=C(NC(=O)\C2=C/C=3NC=CC=3)C2=C1 FIXDPUBAPHNBIB-UYRXBGFRSA-N 0.000 claims 1
- PGMLCEKECCEFAO-AQTBWJFISA-N (3z)-5-[2-(4-hydroxyphenyl)ethynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=CC(=CC=C3NC\2=O)C#CC=2C=CC(O)=CC=2)=C1OC PGMLCEKECCEFAO-AQTBWJFISA-N 0.000 claims 1
- IUCRERMPHUTDKU-GHXNOFRVSA-N (3z)-5-ethynyl-3-[(5-methyl-1h-imidazol-4-yl)methylidene]-1h-indol-2-one Chemical compound N1=CNC(\C=C/2C3=CC(=CC=C3NC\2=O)C#C)=C1C IUCRERMPHUTDKU-GHXNOFRVSA-N 0.000 claims 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- JYQHZYNJTJQVKS-JXAWBTAJSA-N methyl 4-[1-hydroxy-3-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(O)C#CC1=CC=CC(NC\2=O)=C1C/2=C/C1=C(OC)C=CN1 JYQHZYNJTJQVKS-JXAWBTAJSA-N 0.000 claims 1
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 23
- 102000001253 Protein Kinase Human genes 0.000 abstract description 14
- 108060006633 protein kinase Proteins 0.000 abstract description 14
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 2
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 156
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
- 238000000034 method Methods 0.000 description 96
- 239000000243 solution Substances 0.000 description 96
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
- 239000002904 solvent Substances 0.000 description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 62
- 239000007858 starting material Substances 0.000 description 62
- 239000003054 catalyst Substances 0.000 description 56
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 50
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 43
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 31
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- GWGVDNZFTPIGDY-UHFFFAOYSA-M magnesium;ethyne;chloride Chemical compound [Mg+2].[Cl-].[C-]#C GWGVDNZFTPIGDY-UHFFFAOYSA-M 0.000 description 30
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 26
- 239000002244 precipitate Substances 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 22
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 22
- PWXJGBGMFAEGDO-FPLPWBNLSA-N (3z)-4-bromo-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(Br)C=CC=C3NC\2=O)=C1OC PWXJGBGMFAEGDO-FPLPWBNLSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- HDWLGJVJBBRJRT-FPLPWBNLSA-N (3z)-4-iodo-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(I)C=CC=C3NC\2=O)=C1OC HDWLGJVJBBRJRT-FPLPWBNLSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- 238000005859 coupling reaction Methods 0.000 description 17
- 238000003818 flash chromatography Methods 0.000 description 17
- 238000010992 reflux Methods 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 229910004298 SiO 2 Inorganic materials 0.000 description 15
- 229910052786 argon Inorganic materials 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- 238000003556 assay Methods 0.000 description 14
- 230000008878 coupling Effects 0.000 description 13
- 238000010168 coupling process Methods 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 102000004889 Interleukin-6 Human genes 0.000 description 10
- 108090001005 Interleukin-6 Proteins 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 239000000758 substrate Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- 102100023132 Transcription factor Jun Human genes 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 230000005587 bubbling Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical compound O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 8
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical compound COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 7
- NJXYTXADXSRFTJ-UHFFFAOYSA-N 1,2-Dimethoxy-4-vinylbenzene Chemical compound COC1=CC=C(C=C)C=C1OC NJXYTXADXSRFTJ-UHFFFAOYSA-N 0.000 description 6
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 description 6
- 102100030416 Stromelysin-1 Human genes 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 6
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 6
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 6
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 6
- VIMNAEVMZXIKFL-UHFFFAOYSA-N 5-bromo-1,3-dihydroindol-2-one Chemical compound BrC1=CC=C2NC(=O)CC2=C1 VIMNAEVMZXIKFL-UHFFFAOYSA-N 0.000 description 5
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 5
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- NVIBNTUUTHBRCQ-UHFFFAOYSA-N 1-pyridin-2-ylprop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=CC=N1 NVIBNTUUTHBRCQ-UHFFFAOYSA-N 0.000 description 4
- 125000000586 2-(4-morpholinyl)ethoxy group Chemical group [H]C([H])(O*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 4
- SEZFNTZQMWJIAI-UHFFFAOYSA-N 3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one Chemical compound O=C1NC2=CC=CC=C2C1=CC1=CC=CN1 SEZFNTZQMWJIAI-UHFFFAOYSA-N 0.000 description 4
- XQQPPAZTHUEMPF-UHFFFAOYSA-N 4-bromo-1,3-dihydroindol-2-one Chemical compound BrC1=CC=CC2=C1CC(=O)N2 XQQPPAZTHUEMPF-UHFFFAOYSA-N 0.000 description 4
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- XBLWXYZXSFHFGR-UHFFFAOYSA-N methyl 2-(4-formyl-2-methoxyphenoxy)acetate Chemical compound COC(=O)COC1=CC=C(C=O)C=C1OC XBLWXYZXSFHFGR-UHFFFAOYSA-N 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 4
- 235000012141 vanillin Nutrition 0.000 description 4
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 4
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 4
- DZOQJHIDTUABBQ-VBKFSLOCSA-N (3z)-3-(1h-pyrrol-2-ylmethylidene)-5-(2-trimethylsilylethynyl)-1h-indol-2-one Chemical compound C12=CC(C#C[Si](C)(C)C)=CC=C2NC(=O)\C1=C/C1=CC=CN1 DZOQJHIDTUABBQ-VBKFSLOCSA-N 0.000 description 3
- LVZOBVTVBBIVMZ-LGMDPLHJSA-N (3z)-4-[3-(3-chlorophenyl)-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(Cl)C=CC=4)C=CC=C3NC\2=O)=C1OC LVZOBVTVBBIVMZ-LGMDPLHJSA-N 0.000 description 3
- LXCJRPWVKIUJQI-CLFYSBASSA-N (3z)-4-iodo-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=2C(I)=CC=CC=2NC(=O)\C1=C/C1=CC=CN1 LXCJRPWVKIUJQI-CLFYSBASSA-N 0.000 description 3
- YLCIQJHPQCQLFI-XFFZJAGNSA-N (3z)-5-bromo-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C12=CC(Br)=CC=C2NC(=O)\C1=C/C1=CC=CN1 YLCIQJHPQCQLFI-XFFZJAGNSA-N 0.000 description 3
- PWFOQGNZBQZKIB-XFFZJAGNSA-N (3z)-5-iodo-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C12=CC(I)=CC=C2NC(=O)\C1=C/C1=CC=CN1 PWFOQGNZBQZKIB-XFFZJAGNSA-N 0.000 description 3
- GQPONAPNNKBXMX-UHFFFAOYSA-N 1-(1h-pyrrol-2-yl)prop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=CN1 GQPONAPNNKBXMX-UHFFFAOYSA-N 0.000 description 3
- JEWVZAMFDAPMPX-UHFFFAOYSA-N 1-(3-methoxythiophen-2-yl)prop-2-yn-1-ol Chemical compound COC=1C=CSC=1C(O)C#C JEWVZAMFDAPMPX-UHFFFAOYSA-N 0.000 description 3
- KBIAVTUACPKPFJ-UHFFFAOYSA-N 1-ethynyl-4-methoxybenzene Chemical group COC1=CC=C(C#C)C=C1 KBIAVTUACPKPFJ-UHFFFAOYSA-N 0.000 description 3
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 3
- LTQYGSKNLPUXKR-UHFFFAOYSA-N 3-methoxy-1h-pyrrole-2-carbaldehyde Chemical compound COC=1C=CNC=1C=O LTQYGSKNLPUXKR-UHFFFAOYSA-N 0.000 description 3
- KGJDTMQUUPIAEF-UHFFFAOYSA-N 3-methoxythiophene-2-carbaldehyde Chemical compound COC=1C=CSC=1C=O KGJDTMQUUPIAEF-UHFFFAOYSA-N 0.000 description 3
- LAEDNJNAOBPJRP-UHFFFAOYSA-N 4-bromo-5-nitro-1,3-dihydroindol-2-one Chemical compound [O-][N+](=O)C1=CC=C2NC(=O)CC2=C1Br LAEDNJNAOBPJRP-UHFFFAOYSA-N 0.000 description 3
- FSVJYSYFLBFUGF-UHFFFAOYSA-N 4-iodo-1,3-dihydroindol-2-one Chemical compound IC1=CC=CC2=C1CC(=O)N2 FSVJYSYFLBFUGF-UHFFFAOYSA-N 0.000 description 3
- SXMJIZRSNGTEOK-UHFFFAOYSA-N 5-fluoro-4-iodo-1,3-dihydroindol-2-one Chemical compound FC1=CC=C2NC(=O)CC2=C1I SXMJIZRSNGTEOK-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 101710134784 Agnoprotein Proteins 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 3
- 101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 description 3
- 102100033115 Mitogen-activated protein kinase kinase kinase 1 Human genes 0.000 description 3
- 101710164423 Mitogen-activated protein kinase kinase kinase 1 Proteins 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102100040247 Tumor necrosis factor Human genes 0.000 description 3
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001345 alkine derivatives Chemical class 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- RMZDXOGONOSWQE-UHFFFAOYSA-N methyl 2-[4-(1-hydroxyprop-2-ynyl)-2-methoxyphenoxy]acetate Chemical compound COC(=O)COC1=CC=C(C(O)C#C)C=C1OC RMZDXOGONOSWQE-UHFFFAOYSA-N 0.000 description 3
- NUMHUJZXKZKUBN-UHFFFAOYSA-N methyl 4-ethenylbenzoate Chemical compound COC(=O)C1=CC=C(C=C)C=C1 NUMHUJZXKZKUBN-UHFFFAOYSA-N 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910001961 silver nitrate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- QSYPIDOGKIAMIO-OWBHPGMISA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(2-trimethylsilylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#C[Si](C)(C)C)C=CC=C3NC\2=O)=C1OC QSYPIDOGKIAMIO-OWBHPGMISA-N 0.000 description 2
- XWDAYWGNKHFMGK-GDNBJRDFSA-N (3z)-3-[(5-methyl-1h-imidazol-4-yl)methylidene]-5-(2-trimethylsilylethynyl)-1h-indol-2-one Chemical compound N1=CNC(\C=C/2C3=CC(=CC=C3NC\2=O)C#C[Si](C)(C)C)=C1C XWDAYWGNKHFMGK-GDNBJRDFSA-N 0.000 description 2
- IEMHQFOFIAWLHH-VAVYRGOBSA-N (3z)-4-[(e)-2-(4-methoxyphenyl)ethenyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=CC(OC)=CC=C1\C=C\C1=CC=CC(NC\2=O)=C1C/2=C/C1=CC=CN1 IEMHQFOFIAWLHH-VAVYRGOBSA-N 0.000 description 2
- VZTPERKYAXGASO-SREVYHEPSA-N (3z)-4-bromo-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-5-nitro-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(Br)C(=CC=C3NC\2=O)[N+]([O-])=O)=C1OC VZTPERKYAXGASO-SREVYHEPSA-N 0.000 description 2
- PNAHCONZXVUJRQ-LUAWRHEFSA-N (3z)-4-ethynyl-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#C)C=CC=C3NC\2=O)=C1OC PNAHCONZXVUJRQ-LUAWRHEFSA-N 0.000 description 2
- OUIATLHATROJIS-UYRXBGFRSA-N (3z)-5-[2-(4-hydroxyphenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=CC(O)=CC=C1C#CC1=CC=C(NC(=O)\C2=C/C=3NC=CC=3)C2=C1 OUIATLHATROJIS-UYRXBGFRSA-N 0.000 description 2
- ATVKSANJAPEZRZ-YHYXMXQVSA-N (3z)-5-bromo-3-[(5-methyl-1h-imidazol-4-yl)methylidene]-1h-indol-2-one Chemical compound N1=CNC(\C=C/2C3=CC(Br)=CC=C3NC\2=O)=C1C ATVKSANJAPEZRZ-YHYXMXQVSA-N 0.000 description 2
- HFMJJTRZBNUCKY-UHFFFAOYSA-N 1-(1-methylpyrrol-2-yl)prop-2-yn-1-ol Chemical compound CN1C=CC=C1C(O)C#C HFMJJTRZBNUCKY-UHFFFAOYSA-N 0.000 description 2
- VYAJTMNLGWASOE-UHFFFAOYSA-N 1-(4-aminophenyl)prop-2-yn-1-ol Chemical compound NC1=CC=C(C(O)C#C)C=C1 VYAJTMNLGWASOE-UHFFFAOYSA-N 0.000 description 2
- OUKQTRFCDKSEPL-UHFFFAOYSA-N 1-Methyl-2-pyrrolecarboxaldehyde Chemical compound CN1C=CC=C1C=O OUKQTRFCDKSEPL-UHFFFAOYSA-N 0.000 description 2
- YQEHAHXOJGYJDW-UHFFFAOYSA-N 1-pyridin-3-ylprop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=CN=C1 YQEHAHXOJGYJDW-UHFFFAOYSA-N 0.000 description 2
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- JIVGSHFYXPRRSZ-UHFFFAOYSA-N 2,3-dimethoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1OC JIVGSHFYXPRRSZ-UHFFFAOYSA-N 0.000 description 2
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 2
- RWDVOBMEZLLUNU-UHFFFAOYSA-N 3-ethynylindol-2-one Chemical compound O=C1N=c2ccccc2=C1C#C RWDVOBMEZLLUNU-UHFFFAOYSA-N 0.000 description 2
- CLRPXACRDTXENY-UHFFFAOYSA-N 3-ethynylpyridine Chemical compound C#CC1=CC=CN=C1 CLRPXACRDTXENY-UHFFFAOYSA-N 0.000 description 2
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 2
- JKXHPYSLLHSPDF-UHFFFAOYSA-N 3-methoxy-4-(2-morpholin-4-ylethoxy)benzaldehyde Chemical compound COC1=CC(C=O)=CC=C1OCCN1CCOCC1 JKXHPYSLLHSPDF-UHFFFAOYSA-N 0.000 description 2
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 2
- IGXUUWYVUGBMFT-UHFFFAOYSA-N 3-methyleneoxindole Chemical compound C1=CC=C2C(=C)C(=O)NC2=C1 IGXUUWYVUGBMFT-UHFFFAOYSA-N 0.000 description 2
- IQGRDOOZCQXVIC-UHFFFAOYSA-N 4-(1-hydroxyprop-2-ynyl)phenol Chemical compound C#CC(O)C1=CC=C(O)C=C1 IQGRDOOZCQXVIC-UHFFFAOYSA-N 0.000 description 2
- FGLXMUOMJOHGKH-UHFFFAOYSA-N 4-(2-morpholin-4-ylethoxy)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCCN1CCOCC1 FGLXMUOMJOHGKH-UHFFFAOYSA-N 0.000 description 2
- GOUHYARYYWKXHS-UHFFFAOYSA-N 4-formylbenzoic acid Chemical compound OC(=O)C1=CC=C(C=O)C=C1 GOUHYARYYWKXHS-UHFFFAOYSA-N 0.000 description 2
- OMAAUZCBEFAWFW-UHFFFAOYSA-N 4-iodo-5-nitro-1,3-dihydroindol-2-one Chemical compound [O-][N+](=O)C1=CC=C2NC(=O)CC2=C1I OMAAUZCBEFAWFW-UHFFFAOYSA-N 0.000 description 2
- VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 description 2
- HXBLAUNKOYPVCA-UHFFFAOYSA-N 5-(1-hydroxyprop-2-ynyl)-2-methoxyphenol Chemical compound COC1=CC=C(C(O)C#C)C=C1O HXBLAUNKOYPVCA-UHFFFAOYSA-N 0.000 description 2
- QFZSWGXJGXPYMJ-UHFFFAOYSA-N 5-prop-2-ynylphenanthridin-6-one Chemical compound C1=CC=C2C(=O)N(CC#C)C3=CC=CC=C3C2=C1 QFZSWGXJGXPYMJ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 101000701497 Homo sapiens STE20/SPS1-related proline-alanine-rich protein kinase Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 2
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 102100030491 STE20/SPS1-related proline-alanine-rich protein kinase Human genes 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- JVTZFYYHCGSXJV-UHFFFAOYSA-N isovanillin Chemical compound COC1=CC=C(C=O)C=C1O JVTZFYYHCGSXJV-UHFFFAOYSA-N 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical compound CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- UNJWVVJSFUIFBQ-UHFFFAOYSA-N n-[4-(1-hydroxyprop-2-ynyl)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C(O)C#C)C=C1 UNJWVVJSFUIFBQ-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000005623 oxindoles Chemical class 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 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
- 230000037361 pathway Effects 0.000 description 2
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 2
- 230000000865 phosphorylative effect Effects 0.000 description 2
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical group O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 2
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- TZONEPGXYVZUKR-UHFFFAOYSA-N tert-butyl 2-(4-formylphenoxy)acetate Chemical compound CC(C)(C)OC(=O)COC1=CC=C(C=O)C=C1 TZONEPGXYVZUKR-UHFFFAOYSA-N 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- CNELYFGFVRCQQO-ATVHPVEESA-N (3z)-3-(1h-pyrrol-2-ylmethylidene)-5-(2-thiophen-2-ylethynyl)-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C#CC=3SC=CC=3)C=C2\C1=C\C1=CC=CN1 CNELYFGFVRCQQO-ATVHPVEESA-N 0.000 description 1
- YRXDNKVXUTYODU-SQFISAMPSA-N (3z)-4-[3-hydroxy-3-(1-methylpyrrol-2-yl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4N(C=CC=4)C)C=CC=C3NC\2=O)=C1OC YRXDNKVXUTYODU-SQFISAMPSA-N 0.000 description 1
- WAAWIJUGVVCBCM-CLFYSBASSA-N (3z)-4-bromo-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=2C(Br)=CC=CC=2NC(=O)\C1=C/C1=CC=CN1 WAAWIJUGVVCBCM-CLFYSBASSA-N 0.000 description 1
- UMVXEEDGNPDOFC-UYRXBGFRSA-N (3z)-5-[2-(3-hydroxyphenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound OC1=CC=CC(C#CC=2C=C3C(=C/C=4NC=CC=4)/C(=O)NC3=CC=2)=C1 UMVXEEDGNPDOFC-UYRXBGFRSA-N 0.000 description 1
- SDORKXKUPWJUFE-YFHOEESVSA-N (3z)-5-bromo-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=CC(Br)=CC=C3NC\2=O)=C1OC SDORKXKUPWJUFE-YFHOEESVSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 1
- CDLISZQDFZDWQT-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)prop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=C2OCOC2=C1 CDLISZQDFZDWQT-UHFFFAOYSA-N 0.000 description 1
- SFVGIOCAIBDDOH-UHFFFAOYSA-N 1-(2,3-dimethoxyphenyl)prop-2-yn-1-ol Chemical compound COC1=CC=CC(C(O)C#C)=C1OC SFVGIOCAIBDDOH-UHFFFAOYSA-N 0.000 description 1
- QPXUKUBWQSIORQ-UHFFFAOYSA-N 1-(2,4,5-trimethoxyphenyl)prop-2-yn-1-ol Chemical compound COC1=CC(OC)=C(C(O)C#C)C=C1OC QPXUKUBWQSIORQ-UHFFFAOYSA-N 0.000 description 1
- QSTWINSINQGTDH-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)prop-2-yn-1-ol Chemical compound COC1=CC=C(C(O)C#C)C=C1OC QSTWINSINQGTDH-UHFFFAOYSA-N 0.000 description 1
- BNPLJHLZNBBYAX-UHFFFAOYSA-N 1-(3-chlorophenyl)prop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=CC(Cl)=C1 BNPLJHLZNBBYAX-UHFFFAOYSA-N 0.000 description 1
- WACRSIOBIWTUMX-UHFFFAOYSA-N 1-(3-nitrophenyl)prop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=CC([N+]([O-])=O)=C1 WACRSIOBIWTUMX-UHFFFAOYSA-N 0.000 description 1
- PDUTVNAUVBKDTF-UHFFFAOYSA-N 1-(4-nitrophenyl)prop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=C([N+]([O-])=O)C=C1 PDUTVNAUVBKDTF-UHFFFAOYSA-N 0.000 description 1
- ZGCGNJYQFQSIFY-UHFFFAOYSA-N 1-(7-methoxy-1,3-benzodioxol-5-yl)prop-2-yn-1-ol Chemical compound COC1=CC(C(O)C#C)=CC2=C1OCO2 ZGCGNJYQFQSIFY-UHFFFAOYSA-N 0.000 description 1
- PIWITEMMCKUHPI-UHFFFAOYSA-N 1-[4-(dimethylamino)phenyl]prop-2-yn-1-ol Chemical compound CN(C)C1=CC=C(C(O)C#C)C=C1 PIWITEMMCKUHPI-UHFFFAOYSA-N 0.000 description 1
- IOVTVUABZQXKRJ-UHFFFAOYSA-N 1-[4-chloro-2-(methylsulfanylmethoxy)phenyl]prop-2-yn-1-ol Chemical compound CSCOC1=CC(Cl)=CC=C1C(O)C#C IOVTVUABZQXKRJ-UHFFFAOYSA-N 0.000 description 1
- ORPVVAKYSXQCJI-UHFFFAOYSA-N 1-bromo-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Br ORPVVAKYSXQCJI-UHFFFAOYSA-N 0.000 description 1
- QPTLYMZPCLYBTQ-UHFFFAOYSA-N 1-hydroxy-4-iodo-3h-indol-2-one Chemical compound C1=CC=C(I)C2=C1N(O)C(=O)C2 QPTLYMZPCLYBTQ-UHFFFAOYSA-N 0.000 description 1
- CBYAZOKPJYBCHE-UHFFFAOYSA-N 1-iodo-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(I)=C1 CBYAZOKPJYBCHE-UHFFFAOYSA-N 0.000 description 1
- SCCCFNJTCDSLCY-UHFFFAOYSA-N 1-iodo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(I)C=C1 SCCCFNJTCDSLCY-UHFFFAOYSA-N 0.000 description 1
- OCGGBKUCKYBJSC-UHFFFAOYSA-N 1-phenylbut-3-yn-2-ol Chemical compound C#CC(O)CC1=CC=CC=C1 OCGGBKUCKYBJSC-UHFFFAOYSA-N 0.000 description 1
- UIGLAZDLBZDVBL-UHFFFAOYSA-N 1-phenylprop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=CC=C1 UIGLAZDLBZDVBL-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
- 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 1
- JVKRKMWZYMKVTQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JVKRKMWZYMKVTQ-UHFFFAOYSA-N 0.000 description 1
- ISRGONDNXBCDBM-UHFFFAOYSA-N 2-chlorostyrene Chemical compound ClC1=CC=CC=C1C=C ISRGONDNXBCDBM-UHFFFAOYSA-N 0.000 description 1
- NHUBNHMFXQNNMV-UHFFFAOYSA-N 2-ethynylpyridine Chemical compound C#CC1=CC=CC=N1 NHUBNHMFXQNNMV-UHFFFAOYSA-N 0.000 description 1
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- AJYXPNIENRLELY-UHFFFAOYSA-N 2-thiophen-2-ylacetyl chloride Chemical compound ClC(=O)CC1=CC=CS1 AJYXPNIENRLELY-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- KGVFSOOCHJADLR-UHFFFAOYSA-N 3-(1-hydroxyprop-2-ynyl)phenol Chemical compound C#CC(O)C1=CC=CC(O)=C1 KGVFSOOCHJADLR-UHFFFAOYSA-N 0.000 description 1
- QZDYBBOJLGCMGC-UHFFFAOYSA-N 3-(2-methoxyphenyl)prop-1-yn-1-ol Chemical compound COC1=CC=CC=C1CC#CO QZDYBBOJLGCMGC-UHFFFAOYSA-N 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- QMGVGOZRXUJYCB-UHFFFAOYSA-N 3-(3-methoxyphenyl)prop-1-yn-1-ol Chemical compound COC1=CC=CC(CC#CO)=C1 QMGVGOZRXUJYCB-UHFFFAOYSA-N 0.000 description 1
- VFRYWNKBMCTSEA-UHFFFAOYSA-N 3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(C=C2C3=CC=CC=C3NC2=O)=C1OC VFRYWNKBMCTSEA-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
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- FXTKWBZFNQHAAO-UHFFFAOYSA-N 3-iodophenol Chemical compound OC1=CC=CC(I)=C1 FXTKWBZFNQHAAO-UHFFFAOYSA-N 0.000 description 1
- OTODBDQJLMYYKQ-UHFFFAOYSA-N 3-methoxy-1h-pyrrole Chemical compound COC=1C=CNC=1 OTODBDQJLMYYKQ-UHFFFAOYSA-N 0.000 description 1
- RFSKGCVUDQRZSD-UHFFFAOYSA-N 3-methoxythiophene Chemical compound COC=1C=CSC=1 RFSKGCVUDQRZSD-UHFFFAOYSA-N 0.000 description 1
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
- GOOWZCCAITUDAS-UHFFFAOYSA-N 3-pyridin-3-ylprop-1-yn-1-ol Chemical compound N1=CC(=CC=C1)CC#CO GOOWZCCAITUDAS-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- AMYDSGYFGRAJGZ-UHFFFAOYSA-N 3-thiophen-2-ylprop-1-yn-1-ol Chemical compound OC#CCc1cccs1 AMYDSGYFGRAJGZ-UHFFFAOYSA-N 0.000 description 1
- JIZCTFWLZZWKDY-UHFFFAOYSA-N 4-(3-hydroxyprop-2-ynyl)phenol Chemical compound OC#CCC1=CC=C(O)C=C1 JIZCTFWLZZWKDY-UHFFFAOYSA-N 0.000 description 1
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
- ZYOHTXKOHWSJMZ-UHFFFAOYSA-N 4-[3-(dimethylamino)propoxy]benzaldehyde Chemical compound CN(C)CCCOC1=CC=C(C=O)C=C1 ZYOHTXKOHWSJMZ-UHFFFAOYSA-N 0.000 description 1
- QJPJQTDYNZXKQF-UHFFFAOYSA-N 4-bromoanisole Chemical compound COC1=CC=C(Br)C=C1 QJPJQTDYNZXKQF-UHFFFAOYSA-N 0.000 description 1
- MPZMVUQGXAOJIK-UHFFFAOYSA-N 4-bromopyridine;hydron;chloride Chemical compound Cl.BrC1=CC=NC=C1 MPZMVUQGXAOJIK-UHFFFAOYSA-N 0.000 description 1
- HTAXOQIVKCKTJR-UHFFFAOYSA-N 4-bromothiophene Chemical compound BrC1=[C]SC=C1 HTAXOQIVKCKTJR-UHFFFAOYSA-N 0.000 description 1
- ZPOHSGZTQSHCOZ-UHFFFAOYSA-N 4-chloro-2-(methylsulfanylmethoxy)benzaldehyde Chemical compound CSCOC1=CC(Cl)=CC=C1C=O ZPOHSGZTQSHCOZ-UHFFFAOYSA-N 0.000 description 1
- LWXFCZXRFBUOOR-UHFFFAOYSA-N 4-chloro-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1O LWXFCZXRFBUOOR-UHFFFAOYSA-N 0.000 description 1
- WDGGTJISKVZXPM-UHFFFAOYSA-N 4-ethynyl-1,3-dihydroindol-2-one Chemical compound C1=CC=C(C#C)C2=C1NC(=O)C2 WDGGTJISKVZXPM-UHFFFAOYSA-N 0.000 description 1
- ONRHFFREBCNLNE-UHFFFAOYSA-N 4-ethynyl-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one Chemical compound C(#C)C1=C2C(C(NC2=CC=C1)=O)=CC=1NC=CC=1 ONRHFFREBCNLNE-UHFFFAOYSA-N 0.000 description 1
- MDAGSTGIBNZRLK-UHFFFAOYSA-N 4-ethynyl-5-(3-hydroxyphenyl)-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one Chemical compound OC1=CC=CC(C=2C(=C3C(=CC=4NC=CC=4)C(=O)NC3=CC=2)C#C)=C1 MDAGSTGIBNZRLK-UHFFFAOYSA-N 0.000 description 1
- BJMPSYHNUKWPGQ-UHFFFAOYSA-N 4-methoxy-1,3-benzodioxole Chemical compound COC1=CC=CC2=C1OCO2 BJMPSYHNUKWPGQ-UHFFFAOYSA-N 0.000 description 1
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
- QWLHJVDRPZNVBS-UHFFFAOYSA-N 4-phenoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OC1=CC=CC=C1 QWLHJVDRPZNVBS-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OEUGDMOJQQLVAZ-UHFFFAOYSA-N 5-Iodoisatin Chemical compound IC1=CC=C2NC(=O)C(=O)C2=C1 OEUGDMOJQQLVAZ-UHFFFAOYSA-N 0.000 description 1
- HMGIMYREXCYYCX-BWAHOGKJSA-N 5-[3-[(3z)-2-oxo-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-5-yl]prop-2-ynyl]phenanthridin-6-one Chemical compound O=C1NC2=CC=C(C#CCN3C(C4=CC=CC=C4C4=CC=CC=C43)=O)C=C2\C1=C\C1=CC=CN1 HMGIMYREXCYYCX-BWAHOGKJSA-N 0.000 description 1
- LOFRBHZYZCIOJO-UHFFFAOYSA-N 7-methoxy-1,3-benzodioxole-5-carbaldehyde Chemical compound COC1=CC(C=O)=CC2=C1OCO2 LOFRBHZYZCIOJO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102000015936 AP-1 transcription factor Human genes 0.000 description 1
- 108050004195 AP-1 transcription factor Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- POASCTOKSHNEBL-UHFFFAOYSA-N BrN1C(C(C2=CC=CC=C12)=CC=1NC=CC1OC)=O Chemical compound BrN1C(C(C2=CC=CC=C12)=CC=1NC=CC1OC)=O POASCTOKSHNEBL-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- QBVALIXKYOFQGQ-UHFFFAOYSA-N CC=1N=CNC1C=C1/C(N(C2=CC=C(C=C12)[Si](C)(C)C)C#C)=O Chemical compound CC=1N=CNC1C=C1/C(N(C2=CC=C(C=C12)[Si](C)(C)C)C#C)=O QBVALIXKYOFQGQ-UHFFFAOYSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 101100513486 Caenorhabditis elegans mkk-4 gene Proteins 0.000 description 1
- 101100421131 Caenorhabditis elegans sek-1 gene Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- GVOUFPWUYJWQSK-UHFFFAOYSA-N Cyclofenil Chemical group C1=CC(OC(=O)C)=CC=C1C(C=1C=CC(OC(C)=O)=CC=1)=C1CCCCC1 GVOUFPWUYJWQSK-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 102100023332 Dual specificity mitogen-activated protein kinase kinase 7 Human genes 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000624594 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 7 Proteins 0.000 description 1
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase 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
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 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 1
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 description 1
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 1
- 229940083963 Peptide antagonist Drugs 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- QDVBXSCTVLLSOC-UHFFFAOYSA-M [1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrol-2-yl]methyl-triphenylphosphanium;iodide Chemical compound [I-].CC(C)(C)OC(=O)N1C=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 QDVBXSCTVLLSOC-UHFFFAOYSA-M 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- JWMLCCRPDOIBAV-UHFFFAOYSA-N chloro(methylsulfanyl)methane Chemical compound CSCCl JWMLCCRPDOIBAV-UHFFFAOYSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 229960002944 cyclofenil Drugs 0.000 description 1
- 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 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 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
- 210000004408 hybridoma Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- JYQHZYNJTJQVKS-UHFFFAOYSA-N methyl 4-[1-hydroxy-3-[3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(O)C#CC1=CC=CC(NC2=O)=C1C2=CC1=C(OC)C=CN1 JYQHZYNJTJQVKS-UHFFFAOYSA-N 0.000 description 1
- QXDWMJQRXWLSDP-UHFFFAOYSA-N methyl 4-chloro-2-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(Cl)C=C1O QXDWMJQRXWLSDP-UHFFFAOYSA-N 0.000 description 1
- FEIOASZZURHTHB-UHFFFAOYSA-N methyl 4-formylbenzoate Chemical compound COC(=O)C1=CC=C(C=O)C=C1 FEIOASZZURHTHB-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- QRPRIOOKPZSVFN-UHFFFAOYSA-M methyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 QRPRIOOKPZSVFN-UHFFFAOYSA-M 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- SEVSMVUOKAMPDO-UHFFFAOYSA-N para-Acetoxybenzaldehyde Natural products CC(=O)OC1=CC=C(C=O)C=C1 SEVSMVUOKAMPDO-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229940081310 piperonal Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 108010053725 prolylvaline Proteins 0.000 description 1
- FWLKYEAOOIPJRL-UHFFFAOYSA-N prop-1-yn-1-ol Chemical compound CC#CO FWLKYEAOOIPJRL-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000012047 saturated solution Substances 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
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 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
- 230000002194 synthesizing effect Effects 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
- 238000003419 tautomerization reaction Methods 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11258998P | 1998-12-17 | 1998-12-17 | |
| US14148299P | 1999-06-29 | 1999-06-29 | |
| US60/141,482 | 1999-06-29 | ||
| US60/112,589 | 1999-06-29 | ||
| PCT/EP1999/009578 WO2000035906A2 (en) | 1998-12-17 | 1999-12-07 | 4- and 5-alkynyloxindoles and 4- and 5-alkenyloxindoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002532490A true JP2002532490A (ja) | 2002-10-02 |
| JP2002532490A5 JP2002532490A5 (enExample) | 2007-08-16 |
Family
ID=26810125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000588166A Pending JP2002532490A (ja) | 1998-12-17 | 1999-12-07 | 4−および5−アルキニルオキシンドールと4−および5−アルケニルオキシンドール |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP1149092B1 (enExample) |
| JP (1) | JP2002532490A (enExample) |
| KR (1) | KR20010087421A (enExample) |
| CN (1) | CN1147486C (enExample) |
| AT (1) | ATE253062T1 (enExample) |
| AU (1) | AU771599B2 (enExample) |
| BR (1) | BR9916272A (enExample) |
| CA (1) | CA2354510A1 (enExample) |
| DE (1) | DE69912479T2 (enExample) |
| DK (1) | DK1149092T3 (enExample) |
| ES (1) | ES2209527T3 (enExample) |
| PT (1) | PT1149092E (enExample) |
| TR (1) | TR200101747T2 (enExample) |
| WO (1) | WO2000035906A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006090698A1 (ja) * | 2005-02-22 | 2006-08-31 | Ono Pharmaceutical Co., Ltd. | キナーゼ阻害薬およびその用途 |
| JP2007528884A (ja) * | 2004-03-12 | 2007-10-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規なシクロアルキル含有5−アシルインドリノン、その製法及びその医薬品としての使用 |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6569868B2 (en) | 1998-04-16 | 2003-05-27 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| MY128450A (en) | 2000-05-24 | 2007-02-28 | Upjohn Co | 1-(pyrrolidin-1-ylmethyl)-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
| EP1294688A2 (en) | 2000-06-02 | 2003-03-26 | Sugen, Inc. | Indolinone derivatives as protein kinase/phosphatase inhibitors |
| CA2414468A1 (en) * | 2000-06-30 | 2002-01-10 | Sugen, Inc. | 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors |
| AU2002255263B2 (en) | 2001-04-16 | 2006-12-14 | Eisai R&D Management Co., Ltd. | Novel 1H-indazole compound |
| US7018999B2 (en) | 2001-05-16 | 2006-03-28 | Cephalon, Inc. | Methods for the treatment and prevention of pain |
| US6599902B2 (en) | 2001-05-30 | 2003-07-29 | Sugen, Inc. | 5-aralkysufonyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors |
| ATE419247T1 (de) | 2001-07-23 | 2009-01-15 | Serono Lab | Arylsulfonamidderivate als hemmer c-jun- terminaler kinasen (jnk) |
| MXPA04002537A (es) * | 2001-10-12 | 2004-05-31 | Warner Lambert Co | Alquinos como inhibidores de metaloproteinasa de matriz. |
| US6962922B2 (en) | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| DE60332215D1 (de) | 2002-02-28 | 2010-06-02 | Eisai R&D Man Co Ltd | Neue indazolverbindungen mit kondensiertem ring |
| US6747147B2 (en) | 2002-03-08 | 2004-06-08 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US6894057B2 (en) | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| IL164209A0 (en) | 2002-05-31 | 2005-12-18 | Eisai Co Ltd | Pyrazole derivatives and pharmaceutical compositions containing the same |
| CA2487948A1 (en) | 2002-06-14 | 2003-12-24 | Applied Research Systems Ars Holding N.V. | Azole methylidene cyanide derivatives and their use as protein kinase modulators |
| BRPI0415773A (pt) | 2003-10-24 | 2006-12-26 | Schering Ag | derivados de indolinona e sua aplicação no tratamento de estados de doença tais como cáncer |
| US7803824B2 (en) | 2004-10-29 | 2010-09-28 | Alcon, Inc. | Use of inhibitors of Jun N-terminal kinases to treat glaucoma |
| US20060094753A1 (en) | 2004-10-29 | 2006-05-04 | Alcon, Inc. | Use of inhibitors of Jun N-terminal kinases for the treatment of glaucomatous retinopathy and ocular diseases |
| KR20080044836A (ko) | 2005-07-15 | 2008-05-21 | 라보라뚜와르 세로노 에스. 에이. | 자궁내막증 치료용 jnk 억제제 |
| BRPI0613042A2 (pt) | 2005-07-15 | 2010-12-14 | Serono Lab | inibidores de jnk para o tratamento de endometriose |
| CN1939922B (zh) * | 2005-09-27 | 2010-10-13 | 天津和美生物技术有限公司 | 可抑制细胞释放肿瘤坏死因子的5H-噻吩[3,4-c]吡咯-4,6-二酮衍生物 |
| US7968572B2 (en) | 2005-10-03 | 2011-06-28 | Ono Pharmaceuticals Co., Ltd. | Nitrogen-containing heterocyclic compound and pharmaceutical application thereof |
| FR2962733B1 (fr) | 2010-07-13 | 2012-08-17 | Michelin Soc Tech | Polymere greffe par des molecules associatives azotees. |
| FR2962729B1 (fr) | 2010-07-13 | 2012-09-21 | Arkema France | Molecules porteuses de groupes associatifs |
| WO2012178015A2 (en) * | 2011-06-24 | 2012-12-27 | Zenobia Therapeutics, Inc. | Lrrk2 inhibitors |
| JP7270590B2 (ja) | 2019-11-27 | 2023-05-10 | 財團法人工業技術研究院 | 自己発電式検出送信装置 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998007695A1 (en) * | 1996-08-23 | 1998-02-26 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
| WO1998050356A1 (en) * | 1997-05-07 | 1998-11-12 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9501567D0 (en) * | 1995-01-26 | 1995-03-15 | Pharmacia Spa | Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors |
| GB9507298D0 (en) * | 1995-04-07 | 1995-05-31 | Pharmacia Spa | Substituted indolylmethylene-oxindale analogues as tyrosine kinase inhibitors |
| US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| GB9610964D0 (en) * | 1996-05-24 | 1996-07-31 | Pharmacia & Upjohn Spa | Substituted tetralylmethylen-oxindole analogues as tyrosine kinase inhibitors |
-
1999
- 1999-12-07 DE DE69912479T patent/DE69912479T2/de not_active Expired - Fee Related
- 1999-12-07 WO PCT/EP1999/009578 patent/WO2000035906A2/en not_active Ceased
- 1999-12-07 CA CA002354510A patent/CA2354510A1/en not_active Abandoned
- 1999-12-07 BR BR9916272-5A patent/BR9916272A/pt not_active IP Right Cessation
- 1999-12-07 EP EP99957341A patent/EP1149092B1/en not_active Expired - Lifetime
- 1999-12-07 AT AT99957341T patent/ATE253062T1/de not_active IP Right Cessation
- 1999-12-07 JP JP2000588166A patent/JP2002532490A/ja active Pending
- 1999-12-07 KR KR1020017007552A patent/KR20010087421A/ko not_active Ceased
- 1999-12-07 CN CNB998146994A patent/CN1147486C/zh not_active Expired - Fee Related
- 1999-12-07 PT PT99957341T patent/PT1149092E/pt unknown
- 1999-12-07 AU AU15076/00A patent/AU771599B2/en not_active Ceased
- 1999-12-07 DK DK99957341T patent/DK1149092T3/da active
- 1999-12-07 ES ES99957341T patent/ES2209527T3/es not_active Expired - Lifetime
- 1999-12-07 TR TR2001/01747T patent/TR200101747T2/xx unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998007695A1 (en) * | 1996-08-23 | 1998-02-26 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
| WO1998050356A1 (en) * | 1997-05-07 | 1998-11-12 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007528884A (ja) * | 2004-03-12 | 2007-10-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規なシクロアルキル含有5−アシルインドリノン、その製法及びその医薬品としての使用 |
| WO2006090698A1 (ja) * | 2005-02-22 | 2006-08-31 | Ono Pharmaceutical Co., Ltd. | キナーゼ阻害薬およびその用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000035906A2 (en) | 2000-06-22 |
| ES2209527T3 (es) | 2004-06-16 |
| EP1149092B1 (en) | 2003-10-29 |
| WO2000035906A3 (en) | 2000-11-09 |
| CN1147486C (zh) | 2004-04-28 |
| CN1331689A (zh) | 2002-01-16 |
| DK1149092T3 (da) | 2004-02-23 |
| EP1149092A2 (en) | 2001-10-31 |
| BR9916272A (pt) | 2001-09-04 |
| DE69912479T2 (de) | 2004-07-22 |
| AU771599B2 (en) | 2004-03-25 |
| KR20010087421A (ko) | 2001-09-15 |
| CA2354510A1 (en) | 2000-06-22 |
| DE69912479D1 (de) | 2003-12-04 |
| TR200101747T2 (tr) | 2001-11-21 |
| AU1507600A (en) | 2000-07-03 |
| ATE253062T1 (de) | 2003-11-15 |
| PT1149092E (pt) | 2004-03-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2002532490A (ja) | 4−および5−アルキニルオキシンドールと4−および5−アルケニルオキシンドール | |
| US6307056B1 (en) | 4-aryloxindoles | |
| KR100738165B1 (ko) | 헤테로방향족 카르복사미드 유도체 및 ikk-2 효소억제제로서의 용도 | |
| JP3746680B2 (ja) | Cdk2阻害剤としてのピラゾロベンゾジアゼピン | |
| US5874427A (en) | Substituted heteroaromatic 5-HT1F agonists | |
| PL180027B1 (pl) | Nowe zwiazki, skondensowane pirolokarboksyanilidy, bedace nowa klasa ligandów receptora mózgowego GABA PL PL PL PL PL PL PL PL | |
| US6252086B1 (en) | 4-alkenyl-and 4-alkynyloxindoles | |
| AU2007334416A1 (en) | Imidazoles as aldosterone synthase inhibitors | |
| JP2000509719A (ja) | 置換されたアザビシクロ化合物、ならびにtnfおよびサイクリックampホスホジエステラーゼ産生の阻害剤としてのそれらの使用 | |
| US5792766A (en) | Imidazo 1,5-c! quinazolines; a new class of GABA brain receptor ligands | |
| JP2002532503A (ja) | プロテインキナーゼ阻害剤としての4,5−ピラジノオキシンドール | |
| CN110337433B (zh) | 用于调节sgk活性的化合物和药物组合物及其方法 | |
| KR20040047946A (ko) | 2환식 화합물 | |
| KR20040104613A (ko) | 인터루킨-4 유전자 발현 억제제로서의 3-치환된아미노-1η-인돌-2-카복실산 및 3-치환된아미노-벤조티오펜-2-카복실산 유도체 | |
| JP2006515355A (ja) | 酵素ikk−2阻害剤としてのチオフェンカルボキサミド | |
| US6313310B1 (en) | 4-and 5-alkynyloxindoles and 4-and 5-alkenyloxindoles | |
| MXPA01006049A (en) | 4- and 5-alkynyloxindoles and 4- and 5-alkenyloxindoles | |
| ZA200104281B (en) | 4- and 5-alkynyloxindoles and 4- and 5-alkenyloxindoles. | |
| CN114276338B (zh) | 2-吡唑-3-苯并咪唑衍生物及其制备方法和应用 | |
| MXPA01006141A (en) | 4-aryloxindoles as inhibitors of jnk protein kinases | |
| ZA200104320B (en) | 4-Aryloxindoles as inhibitors of JNK protein kinases. | |
| TW202417429A (zh) | 用於抑制yap-tead交互作用的新穎雜雙環化合物及包含其之藥學組成物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20061207 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061207 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20070702 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100622 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20101130 |