HRP20030214A2 - Pharmaceutically active sulfonamide derivatives bearing both lipohilic and ionisable moieties as inhibitors of protein junkinases - Google Patents

Info

Publication number

HRP20030214A2

HRP20030214A2 HR20030214A HRP20030214A HRP20030214A2 HR P20030214 A2 HRP20030214 A2 HR P20030214A2 HR 20030214 A HR20030214 A HR 20030214A HR P20030214 A HRP20030214 A HR P20030214A HR P20030214 A2 HRP20030214 A2 HR P20030214A2

Authority

HR

Croatia

Prior art keywords

methyl

sulfonyl

amino

thien

benzamide

Prior art date

2000-09-27

Links

• Espacenet
• Global Dossier
• Discuss

• 229940124530 sulfonamide Drugs 0.000 title claims description 52
• 150000003456 sulfonamides Chemical class 0.000 title claims description 43
• 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 title claims description 17
• 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 title claims description 17
• 239000003112 inhibitor Substances 0.000 title description 6
• -1 nitro, sulfonyl Chemical group 0.000 claims description 77
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 claims description 65
• 239000000203 mixture Substances 0.000 claims description 50
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 44
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 33
• 150000001412 amines Chemical class 0.000 claims description 31
• 238000002360 preparation method Methods 0.000 claims description 26
• 125000003118 aryl group Chemical group 0.000 claims description 23
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 17
• 230000014509 gene expression Effects 0.000 claims description 15
• 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 claims description 13
• 208000035475 disorder Diseases 0.000 claims description 13
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 13
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
• 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 claims description 11
• 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 claims description 11
• 150000002431 hydrogen Chemical group 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 11
• 230000000694 effects Effects 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• HEHMZUQCKMARIT-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)C(F)(F)F)=C1 HEHMZUQCKMARIT-UHFFFAOYSA-N 0.000 claims description 9
• 210000004556 brain Anatomy 0.000 claims description 9
• 208000028867 ischemia Diseases 0.000 claims description 9
• VRJHQPZVIGNGMX-UHFFFAOYSA-N piperidine-4-one Chemical group O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 claims description 9
• 125000001544 thienyl group Chemical group 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 125000000217 alkyl group Chemical group 0.000 claims description 7
• 125000002541 furyl group Chemical group 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 150000002367 halogens Chemical group 0.000 claims description 7
• OGLWFGSKCPERGG-UHFFFAOYSA-N 2-oxo-n-[[5-[4-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-1h-pyridine-3-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C(NC=CC=3)=O)=CC=2)CC1 OGLWFGSKCPERGG-UHFFFAOYSA-N 0.000 claims description 6
• 208000023275 Autoimmune disease Diseases 0.000 claims description 6
• 230000000302 ischemic effect Effects 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• XPPZCVNVUAJANR-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)N(C)CC=2C=CC(=CC=2)C(F)(F)F)=C1 XPPZCVNVUAJANR-UHFFFAOYSA-N 0.000 claims description 5
• 206010028980 Neoplasm Diseases 0.000 claims description 5
• 206010040070 Septic Shock Diseases 0.000 claims description 5
• 125000004423 acyloxy group Chemical group 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 125000004122 cyclic group Chemical group 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 210000002216 heart Anatomy 0.000 claims description 5
• 210000003734 kidney Anatomy 0.000 claims description 5
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 4
• 125000004442 acylamino group Chemical group 0.000 claims description 4
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical group C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 201000006370 kidney failure Diseases 0.000 claims description 4
• 210000004185 liver Anatomy 0.000 claims description 4
• 229910052757 nitrogen Inorganic materials 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 125000005309 thioalkoxy group Chemical group 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
• 208000023105 Huntington disease Diseases 0.000 claims description 3
• 208000018737 Parkinson disease Diseases 0.000 claims description 3
• 206010063837 Reperfusion injury Diseases 0.000 claims description 3
• 230000002159 abnormal effect Effects 0.000 claims description 3
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• 230000006806 disease prevention Effects 0.000 claims description 3
• 206010015037 epilepsy Diseases 0.000 claims description 3
• 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• 208000010125 myocardial infarction Diseases 0.000 claims description 3
• 125000006501 nitrophenyl group Chemical group 0.000 claims description 3
• BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical group NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 claims description 3
• 125000003386 piperidinyl group Chemical group 0.000 claims description 3
• WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 claims description 3
• NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical group NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 claims description 3
• QGKLPGKXAVVPOJ-UHFFFAOYSA-N pyrrolidin-3-one Chemical group O=C1CCNC1 QGKLPGKXAVVPOJ-UHFFFAOYSA-N 0.000 claims description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
• 229920006395 saturated elastomer Polymers 0.000 claims description 3
• 230000036303 septic shock Effects 0.000 claims description 3
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
• ZXDHMWKKHWUGNF-UHFFFAOYSA-N 2-sulfanylidene-n-[[5-[4-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-1h-pyridine-3-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C(NC=CC=3)=S)=CC=2)CC1 ZXDHMWKKHWUGNF-UHFFFAOYSA-N 0.000 claims description 2
• WNDVUNAGTFREDB-UHFFFAOYSA-N 3-methoxy-n-[[5-[3-(2-pyridin-2-ylethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CC(CC2)NCCC=2N=CC=CC=2)=C1 WNDVUNAGTFREDB-UHFFFAOYSA-N 0.000 claims description 2
• KPOIREPMXZFSNV-UHFFFAOYSA-N 3-methoxy-n-[[5-[3-(3-morpholin-4-ylpropylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CC(CC2)NCCCN2CCOCC2)=C1 KPOIREPMXZFSNV-UHFFFAOYSA-N 0.000 claims description 2
• CWRSKSUXNCINND-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(2-pyridin-2-ylethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)NCCC=2N=CC=CC=2)=C1 CWRSKSUXNCINND-UHFFFAOYSA-N 0.000 claims description 2
• AABAJDPRRHYOAV-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(2-pyridin-2-ylethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCC=2N=CC=CC=2)=C1 AABAJDPRRHYOAV-UHFFFAOYSA-N 0.000 claims description 2
• WJVPSLHIPHKJGR-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(3-morpholin-4-ylpropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCCN2CCOCC2)=C1 WJVPSLHIPHKJGR-UHFFFAOYSA-N 0.000 claims description 2
• IEVZPTYBQVKDGM-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(2,3,4,5,6-pentamethylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C(=C(C)C(C)=C(C)C=2C)C)=C1 IEVZPTYBQVKDGM-UHFFFAOYSA-N 0.000 claims description 2
• LKMMJRSDKDNVCD-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-methylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(C)=CC=2)=C1 LKMMJRSDKDNVCD-UHFFFAOYSA-N 0.000 claims description 2
• HWVOMCVAQLMXEP-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-methylsulfonylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)S(C)(=O)=O)=C1 HWVOMCVAQLMXEP-UHFFFAOYSA-N 0.000 claims description 2
• SIPDDBKNGXEADC-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-phenoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 SIPDDBKNGXEADC-UHFFFAOYSA-N 0.000 claims description 2
• YDWAZMSGTWOJKZ-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-propoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(OCCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 YDWAZMSGTWOJKZ-UHFFFAOYSA-N 0.000 claims description 2
• POXCZVSHFWOHHK-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[1-[4-(trifluoromethyl)phenyl]ethylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NC(C)C=2C=CC(=CC=2)C(F)(F)F)=C1 POXCZVSHFWOHHK-UHFFFAOYSA-N 0.000 claims description 2
• WCFANFOWTKGWNV-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[1-[4-(trifluoromethyl)phenyl]propylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(CC)NC(CC1)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 WCFANFOWTKGWNV-UHFFFAOYSA-N 0.000 claims description 2
• IBUQXYBAGPSJJO-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[2-(4-methylphenyl)ethylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCC=2C=CC(C)=CC=2)=C1 IBUQXYBAGPSJJO-UHFFFAOYSA-N 0.000 claims description 2
• UNWNZJPKLZSKCV-RPBOFIJWSA-N 3-methoxy-n-[[5-[4-[[(1s,2r)-2-phenylcyclopropyl]amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)N[C@@H]2[C@H](C2)C=2C=CC=CC=2)=C1 UNWNZJPKLZSKCV-RPBOFIJWSA-N 0.000 claims description 2
• ZWFPICDMSOAGLH-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[2-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C(=CC=CC=2)C(F)(F)F)=C1 ZWFPICDMSOAGLH-UHFFFAOYSA-N 0.000 claims description 2
• HMZNUBAPMAOCOT-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[3-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=C(C=CC=2)C(F)(F)F)=C1 HMZNUBAPMAOCOT-UHFFFAOYSA-N 0.000 claims description 2
• CMSNSJKESAFZTI-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[3-(trifluoromethylsulfanyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=C(SC(F)(F)F)C=CC=2)=C1 CMSNSJKESAFZTI-UHFFFAOYSA-N 0.000 claims description 2
• XPBMHMIVWLMSSJ-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[4-(trifluoromethylsulfanyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(SC(F)(F)F)=CC=2)=C1 XPBMHMIVWLMSSJ-UHFFFAOYSA-N 0.000 claims description 2
• WQYNKWNGMHSGNT-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[6-(trifluoromethyl)pyridin-3-yl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=NC(=CC=2)C(F)(F)F)=C1 WQYNKWNGMHSGNT-UHFFFAOYSA-N 0.000 claims description 2
• BLHCGACBVVBQJQ-GOSISDBHSA-N 4-chloro-n-[[5-[(3r)-3-[(hexylamino)methyl]pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1[C@@H](CNCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 BLHCGACBVVBQJQ-GOSISDBHSA-N 0.000 claims description 2
• ISDZJHKRZJOPFG-GOSISDBHSA-N 4-chloro-n-[[5-[(3r)-3-[[[4-(trifluoromethyl)phenyl]methylamino]methyl]pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNC[C@@H]1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 ISDZJHKRZJOPFG-GOSISDBHSA-N 0.000 claims description 2
• PJRYNEPWNXFQGP-UHFFFAOYSA-N 4-chloro-n-[[5-[2-[[[4-(trifluoromethyl)phenyl]methylamino]methyl]pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNCC1N(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1 PJRYNEPWNXFQGP-UHFFFAOYSA-N 0.000 claims description 2
• ZMWLJQDAWIGXOC-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(2-pyridin-2-ylethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CC(CC2)NCCC=2N=CC=CC=2)S1 ZMWLJQDAWIGXOC-UHFFFAOYSA-N 0.000 claims description 2
• QFDUJWBLOQNNFF-UHFFFAOYSA-N 4-chloro-n-[[5-[3-[(1-hydroxycyclohexyl)methylamino]pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1NCC1(O)CCCCC1 QFDUJWBLOQNNFF-UHFFFAOYSA-N 0.000 claims description 2
• JUECCJMELXTEIW-UHFFFAOYSA-N 4-chloro-n-[[5-[3-[[[4-(trifluoromethyl)phenyl]methylamino]methyl]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNCC1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1 JUECCJMELXTEIW-UHFFFAOYSA-N 0.000 claims description 2
• BNBVRPMOIVJFGS-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[(4-propylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(CCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 BNBVRPMOIVJFGS-UHFFFAOYSA-N 0.000 claims description 2
• OPNYMHLOHHVHJC-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[1-[4-(trifluoromethyl)phenyl]ethylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(C)NC(CC1)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 OPNYMHLOHHVHJC-UHFFFAOYSA-N 0.000 claims description 2
• DIDQABDFIWEKRS-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[2-[4-(trifluoromethyl)phenyl]propan-2-ylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(C)(C)NC(CC1)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 DIDQABDFIWEKRS-UHFFFAOYSA-N 0.000 claims description 2
• ZPKZTRKUOSQDAN-GOSISDBHSA-N 4-chloro-n-[[5-[4-[[(1r)-1-cyclohexylethyl]amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound N([C@H](C)C1CCCCC1)C(CC1)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 ZPKZTRKUOSQDAN-GOSISDBHSA-N 0.000 claims description 2
• JWLSFCHUCJLYLD-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[[4-(trifluoromethoxy)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 JWLSFCHUCJLYLD-UHFFFAOYSA-N 0.000 claims description 2
• BVFJKTWMNUHVDO-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 BVFJKTWMNUHVDO-UHFFFAOYSA-N 0.000 claims description 2
• YRSBUPXJFZUIJU-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[[4-(trifluoromethylsulfanyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(SC(F)(F)F)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 YRSBUPXJFZUIJU-UHFFFAOYSA-N 0.000 claims description 2
• SWWYYUFJDBPSCO-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[hexyl(3-phenylpropyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1N(CCCCCC)CCCC1=CC=CC=C1 SWWYYUFJDBPSCO-UHFFFAOYSA-N 0.000 claims description 2
• SFFWJQKPFTWBOT-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[hexyl(pyridin-4-ylmethyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1N(CCCCCC)CC1=CC=NC=C1 SFFWJQKPFTWBOT-UHFFFAOYSA-N 0.000 claims description 2
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
• 206010019196 Head injury Diseases 0.000 claims description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
• 208000017442 Retinal disease Diseases 0.000 claims description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
• 210000000481 breast Anatomy 0.000 claims description 2
• 210000001072 colon Anatomy 0.000 claims description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 210000004072 lung Anatomy 0.000 claims description 2
• VHUXUXYRKSWDAU-UHFFFAOYSA-N n-[[4-chloro-5-[4-(hexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C1=C(Cl)C=C(CNC(=O)C=2C=C(OC)C=CC=2)S1 VHUXUXYRKSWDAU-UHFFFAOYSA-N 0.000 claims description 2
• AUMSGNKKNYYDPO-UHFFFAOYSA-N n-[[5-[3-(1-adamantylmethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CC(CC2)NCC23CC4CC(CC(C4)C2)C3)=C1 AUMSGNKKNYYDPO-UHFFFAOYSA-N 0.000 claims description 2
• HAXYDEDKPDXTRY-UHFFFAOYSA-N n-[[5-[3-(1-adamantylmethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CC(CC2)NCC23CC4CC(CC(C4)C2)C3)S1 HAXYDEDKPDXTRY-UHFFFAOYSA-N 0.000 claims description 2
• PEDDBRJLQYOUOZ-UHFFFAOYSA-N n-[[5-[3-(2-cyclohexylethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CC(CC2)NCCC2CCCCC2)=C1 PEDDBRJLQYOUOZ-UHFFFAOYSA-N 0.000 claims description 2
• UJZBPGBILAFJTQ-UHFFFAOYSA-N n-[[5-[3-(butylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1C(NCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 UJZBPGBILAFJTQ-UHFFFAOYSA-N 0.000 claims description 2
• BJCCBOGODWMYNF-ITUIMRKVSA-N n-[[5-[3-[[(1r)-1-cyclohexylethyl]amino]pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CC(CC2)N[C@H](C)C2CCCCC2)=C1 BJCCBOGODWMYNF-ITUIMRKVSA-N 0.000 claims description 2
• BDTCTRHEDIAZLI-WEWZKHDXSA-N n-[[5-[3-[[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]amino]pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound N([C@H]1[C@]2([H])CC[C@@](C2)(C1)[H])C(C1)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 BDTCTRHEDIAZLI-WEWZKHDXSA-N 0.000 claims description 2
• BYZMUFLFKDVUJW-UHFFFAOYSA-N n-[[5-[4-(2,3-dihydro-1,4-benzodioxin-6-ylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=C3OCCOC3=CC=2)=C1 BYZMUFLFKDVUJW-UHFFFAOYSA-N 0.000 claims description 2
• UFPYTBMPRFMEQT-UHFFFAOYSA-N n-[[5-[4-(2,3-dihydro-1-benzofuran-5-ylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=C3CCOC3=CC=2)=C1 UFPYTBMPRFMEQT-UHFFFAOYSA-N 0.000 claims description 2
• KLYZWURVWSWFLY-UHFFFAOYSA-N n-[[5-[4-(2-cyclohexylethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCC2CCCCC2)=C1 KLYZWURVWSWFLY-UHFFFAOYSA-N 0.000 claims description 2
• CKXLOOSPQMRJMK-UHFFFAOYSA-N n-[[5-[4-(3,3-diethoxypropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCC(OCC)OCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 CKXLOOSPQMRJMK-UHFFFAOYSA-N 0.000 claims description 2
• IJSNIBWPXCQGHM-UHFFFAOYSA-N n-[[5-[4-(benzylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC=CC=2)=C1 IJSNIBWPXCQGHM-UHFFFAOYSA-N 0.000 claims description 2
• QRMFLENACLOUIF-UHFFFAOYSA-N n-[[5-[4-(butylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-2-oxo-1h-pyridine-3-carboxamide Chemical compound C1CC(NCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CNC1=O QRMFLENACLOUIF-UHFFFAOYSA-N 0.000 claims description 2
• QUPGNQAAPYBLQS-UHFFFAOYSA-N n-[[5-[4-(hexylamino)piperidin-1-yl]sulfonyl-4-[hydroxy(phenyl)methyl]thiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C1=C(C(O)C=2C=CC=CC=2)C=C(CNC(=O)C=2C=C(OC)C=CC=2)S1 QUPGNQAAPYBLQS-UHFFFAOYSA-N 0.000 claims description 2
• GCTUKULTSHXALR-UHFFFAOYSA-N n-[[5-[4-(hexylamino)piperidin-1-yl]sulfonyl-4-trimethylsilylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C1=C([Si](C)(C)C)C=C(CNC(=O)C=2C=C(OC)C=CC=2)S1 GCTUKULTSHXALR-UHFFFAOYSA-N 0.000 claims description 2
• YHENMXCQEQDMCT-UHFFFAOYSA-N n-[[5-[4-(hexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-2-sulfanylidene-1h-pyridine-3-carboxamide Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CNC1=S YHENMXCQEQDMCT-UHFFFAOYSA-N 0.000 claims description 2
• IHASYAHJFDYBCN-UHFFFAOYSA-N n-[[5-[4-[(2,2-difluoro-1,3-benzodioxol-5-yl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=C3OC(F)(F)OC3=CC=2)=C1 IHASYAHJFDYBCN-UHFFFAOYSA-N 0.000 claims description 2
• IYOIXTJUBKEFFP-UHFFFAOYSA-N n-[[5-[4-[(4-butoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1=CC(OCCCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 IYOIXTJUBKEFFP-UHFFFAOYSA-N 0.000 claims description 2
• NMGGSYPIVVODTC-UHFFFAOYSA-N n-[[5-[4-[(4-ethylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1=CC(CC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 NMGGSYPIVVODTC-UHFFFAOYSA-N 0.000 claims description 2
• DVOAIIHBNXHFHN-UHFFFAOYSA-N n-[[5-[4-[(4-ethylsulfanylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1=CC(SCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 DVOAIIHBNXHFHN-UHFFFAOYSA-N 0.000 claims description 2
• JNSJAYIEHBECRH-UHFFFAOYSA-N n-[[5-[4-[(5-bromofuran-2-yl)methyl-hexylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1N(CCCCCC)CC1=CC=C(Br)O1 JNSJAYIEHBECRH-UHFFFAOYSA-N 0.000 claims description 2
• MQVGWGTYVZGDHS-UHFFFAOYSA-N n-[[5-[4-[2-(4-hydroxyphenyl)ethylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCC=2C=CC(O)=CC=2)=C1 MQVGWGTYVZGDHS-UHFFFAOYSA-N 0.000 claims description 2
• IYMXZYMDKGDVCP-PPUHSXQSSA-N n-[[5-[4-[[(1r)-1-cyclohexylethyl]amino]azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)N[C@H](C)C2CCCCC2)=C1 IYMXZYMDKGDVCP-PPUHSXQSSA-N 0.000 claims description 2
• WJRKVPQBYULJLZ-LJQANCHMSA-N n-[[5-[4-[[(1r)-1-cyclohexylethyl]amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)N[C@H](C)C2CCCCC2)=C1 WJRKVPQBYULJLZ-LJQANCHMSA-N 0.000 claims description 2
• SPYAWOKUARADJQ-GDHBDLSCSA-N n-[[5-[4-[[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]amino]azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound N([C@H]1[C@]2([H])CC[C@@](C2)(C1)[H])C(CC1)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 SPYAWOKUARADJQ-GDHBDLSCSA-N 0.000 claims description 2
• FJRFRBOTFXORHP-WTUOIENSSA-N n-[[5-[4-[[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]amino]azepan-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound N([C@H]1[C@]2([H])CC[C@@](C2)(C1)[H])C(CC1)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 FJRFRBOTFXORHP-WTUOIENSSA-N 0.000 claims description 2
• MHXQUNHXLFOURQ-YZZKKUAISA-N n-[[5-[4-[[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound N([C@H]1[C@]2([H])CC[C@@](C2)(C1)[H])C(CC1)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 MHXQUNHXLFOURQ-YZZKKUAISA-N 0.000 claims description 2
• PAINNEQTKSSEME-AQOAWAETSA-N n-[[5-[4-[[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound N([C@H]1[C@]2([H])CC[C@@](C2)(C1)[H])C(CC1)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 PAINNEQTKSSEME-AQOAWAETSA-N 0.000 claims description 2
• QFYMBOHCUQXBMB-UHFFFAOYSA-N n-[[5-[4-[[2,5-bis(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C(=CC=C(C=2)C(F)(F)F)C(F)(F)F)=C1 QFYMBOHCUQXBMB-UHFFFAOYSA-N 0.000 claims description 2
• BGFKIMXHVHKPNG-UHFFFAOYSA-N n-[[5-[4-[[4-(difluoromethoxy)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(OC(F)F)=CC=2)=C1 BGFKIMXHVHKPNG-UHFFFAOYSA-N 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 210000000056 organ Anatomy 0.000 claims description 2
• 125000004043 oxo group Chemical group O=* 0.000 claims description 2
• 239000001301 oxygen Substances 0.000 claims description 2
• 230000037361 pathway Effects 0.000 claims description 2
• 210000002307 prostate Anatomy 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• 238000006268 reductive amination reaction Methods 0.000 claims description 2
• 208000020431 spinal cord injury Diseases 0.000 claims description 2
• 125000004434 sulfur atom Chemical group 0.000 claims description 2
• 210000001550 testis Anatomy 0.000 claims description 2
• HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims 14
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 4
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 3
• 102000019145 JUN kinase activity proteins Human genes 0.000 claims 2
• 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims 1
• WFCHEWUYHIIPDU-UHFFFAOYSA-N 3-methoxy-N-[[5-[4-[[4-(2-methylpropyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide 3-methoxy-N-[[5-[4-[(4-propan-2-ylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C(C(C)C)C1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1.C(C)(C)C1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1 WFCHEWUYHIIPDU-UHFFFAOYSA-N 0.000 claims 1
• WKAUASPRERVXBS-UHFFFAOYSA-N 4-chloro-N-[[5-[4-[[4-(difluoromethoxy)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide 4-chloro-N-[[5-[4-[(4-propoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)OCCC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)OC(F)F)C=C1 WKAUASPRERVXBS-UHFFFAOYSA-N 0.000 claims 1
• NQGJYCKIXCESDA-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-cyclohexylethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide;4-chloro-n-[[5-[4-(cyclohexylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCC2CCCCC2)S1.C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCCC2CCCCC2)S1 NQGJYCKIXCESDA-UHFFFAOYSA-N 0.000 claims 1
• PEOPOFHAAWDBLO-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-ethylhexylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide;4-chloro-n-[[5-[4-(2-propoxyethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCOCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1.C1CC(NCC(CC)CCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 PEOPOFHAAWDBLO-UHFFFAOYSA-N 0.000 claims 1
• ZZAINDHFFCGOPR-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-ethylhexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide;4-chloro-n-[[5-[4-(3-imidazol-1-ylpropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCC(CC)CCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1.C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCCCN2C=NC=C2)S1 ZZAINDHFFCGOPR-UHFFFAOYSA-N 0.000 claims 1
• BSYLQPYKXIPKGD-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(heptylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide;4-chloro-n-[[5-[4-(octylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1.C1CC(NCCCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 BSYLQPYKXIPKGD-UHFFFAOYSA-N 0.000 claims 1
• ZAJCFNGTGLBWQU-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(hexylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide;n-[[5-[4-(hexylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1.C1CC(NCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 ZAJCFNGTGLBWQU-UHFFFAOYSA-N 0.000 claims 1
• NGVMCDWZEGDTKT-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(octylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide;n-[[5-[4-(heptylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1.C1CC(NCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 NGVMCDWZEGDTKT-UHFFFAOYSA-N 0.000 claims 1
• SBTVUGWQXLXMON-UHFFFAOYSA-N 5-[[(3-methoxybenzoyl)amino]methyl]-2-[4-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophene-3-carboxylic acid Chemical class COC1=CC=CC(C(=O)NCC=2SC(=C(C(O)=O)C=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)C(F)(F)F)=C1 SBTVUGWQXLXMON-UHFFFAOYSA-N 0.000 claims 1
• DSRHCPAMEKHQLU-UHFFFAOYSA-N C(C)C(CNC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O)CCCC.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCN2CCCCC2)C=CC1 Chemical compound C(C)C(CNC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O)CCCC.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCN2CCCCC2)C=CC1 DSRHCPAMEKHQLU-UHFFFAOYSA-N 0.000 claims 1
• XRYLCMKFQVPZOQ-UHFFFAOYSA-N C(C)C(CNC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O)CCCC.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCN2CCCCC2)C=CC1 Chemical compound C(C)C(CNC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O)CCCC.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCN2CCCCC2)C=CC1 XRYLCMKFQVPZOQ-UHFFFAOYSA-N 0.000 claims 1
• YWTIDRAHRAMOCK-UHFFFAOYSA-N C(C)OC=1C=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=CC1.C(C)(C)(C)C1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1 Chemical compound C(C)OC=1C=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=CC1.C(C)(C)(C)C1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1 YWTIDRAHRAMOCK-UHFFFAOYSA-N 0.000 claims 1
• SWJYEAFPMGNSCW-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1.IC1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1 Chemical compound C(C1=CC=CC=C1)OC1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1.IC1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1 SWJYEAFPMGNSCW-UHFFFAOYSA-N 0.000 claims 1
• SYGKFXFHPPDWSX-UHFFFAOYSA-N C(CCC)N(C1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC=C(C=C1)Cl)=O)CCCCCC.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)N(CC2=NC=CC=C2)CCCCCC)C=C1 Chemical compound C(CCC)N(C1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC=C(C=C1)Cl)=O)CCCCCC.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)N(CC2=NC=CC=C2)CCCCCC)C=C1 SYGKFXFHPPDWSX-UHFFFAOYSA-N 0.000 claims 1
• NJARXDSIZAEXHI-UHFFFAOYSA-N C(CCC)NC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCCC)C=CC1 Chemical compound C(CCC)NC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCCC)C=CC1 NJARXDSIZAEXHI-UHFFFAOYSA-N 0.000 claims 1
• LHNKGTSELYJPAR-UHFFFAOYSA-N C(CCC)NC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC=C(C=C1)Cl)=O.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCCC)C=C1 Chemical compound C(CCC)NC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC=C(C=C1)Cl)=O.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCCC)C=C1 LHNKGTSELYJPAR-UHFFFAOYSA-N 0.000 claims 1
• KPCDPHLMTCKJHG-UHFFFAOYSA-N C(CCC)NCCC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)CNCCCCC)C=CC1 Chemical compound C(CCC)NCCC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)CNCCCCC)C=CC1 KPCDPHLMTCKJHG-UHFFFAOYSA-N 0.000 claims 1
• FTNAEWJPIYDXOH-UHFFFAOYSA-N C(CCCCCCCCCCC)NC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.C(CCC)NC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O Chemical compound C(CCCCCCCCCCC)NC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.C(CCC)NC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O FTNAEWJPIYDXOH-UHFFFAOYSA-N 0.000 claims 1
• KPSXKPCPLCJJTO-UHFFFAOYSA-N C(CCCCCCCCCCC)NC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.C(CCC)NC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O Chemical compound C(CCCCCCCCCCC)NC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.C(CCC)NC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O KPSXKPCPLCJJTO-UHFFFAOYSA-N 0.000 claims 1
• XDZFSTANHRHTNF-UHFFFAOYSA-N C1(CCCCC1)CCNC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.C(CCCCCCCCCCC)NC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O Chemical compound C1(CCCCC1)CCNC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.C(CCCCCCCCCCC)NC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O XDZFSTANHRHTNF-UHFFFAOYSA-N 0.000 claims 1
• TXKUYCQAMIHGTH-UHFFFAOYSA-N C1(CCCCC1)CNC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCOCCC)C=CC1 Chemical compound C1(CCCCC1)CNC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCOCCC)C=CC1 TXKUYCQAMIHGTH-UHFFFAOYSA-N 0.000 claims 1
• MTJSBUNJOGUNFV-UHFFFAOYSA-N C1(CCCCC1)CNC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCOCCC)C=CC1 Chemical compound C1(CCCCC1)CNC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCOCCC)C=CC1 MTJSBUNJOGUNFV-UHFFFAOYSA-N 0.000 claims 1
• RBZWEWBNJGJGOE-UHFFFAOYSA-N C12(CC3CC(CC(C1)C3)C2)CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O.COC=2C=C(C(=O)NCC=3SC(=CC3)S(=O)(=O)N3CCC(CC3)NCCOCCC)C=CC2 Chemical compound C12(CC3CC(CC(C1)C3)C2)CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O.COC=2C=C(C(=O)NCC=3SC(=CC3)S(=O)(=O)N3CCC(CC3)NCCOCCC)C=CC2 RBZWEWBNJGJGOE-UHFFFAOYSA-N 0.000 claims 1
• VJRWERKXULJQBL-UHFFFAOYSA-N C12(CC3CC(CC(C1)C3)C2)CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC=C(C=C2)Cl)=O.ClC2=CC=C(C(=O)NCC=3SC(=CC3)S(=O)(=O)N3CCC(CC3)NCCOCCC)C=C2 Chemical compound C12(CC3CC(CC(C1)C3)C2)CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC=C(C=C2)Cl)=O.ClC2=CC=C(C(=O)NCC=3SC(=CC3)S(=O)(=O)N3CCC(CC3)NCCOCCC)C=C2 VJRWERKXULJQBL-UHFFFAOYSA-N 0.000 claims 1
• FWDUMNGFXOFGPP-ANQAEFHNSA-N C1C(NCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1.C1C(NCCCCCC)C[C@@H](C(=O)OC)N1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 Chemical compound C1C(NCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1.C1C(NCCCCCC)C[C@@H](C(=O)OC)N1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 FWDUMNGFXOFGPP-ANQAEFHNSA-N 0.000 claims 1
• JQVGRJITXWFCGI-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC(C)C2=CC=CC=C2)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=CC3=CC=CC=C23)C=CC1 Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC(C)C2=CC=CC=C2)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=CC3=CC=CC=C23)C=CC1 JQVGRJITXWFCGI-UHFFFAOYSA-N 0.000 claims 1
• FAKDGTHTOWXSQR-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)C(F)(F)F)C=CC1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCCC)C=C1 Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)C(F)(F)F)C=CC1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCCC)C=C1 FAKDGTHTOWXSQR-UHFFFAOYSA-N 0.000 claims 1
• PXAHICKLCKFUCB-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)CCC)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC(=CC=C2)C)C=CC1 Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)CCC)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC(=CC=C2)C)C=CC1 PXAHICKLCKFUCB-UHFFFAOYSA-N 0.000 claims 1
• YIYFDCRUODICCL-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=NC=C2)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)OC)C=CC1 Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=NC=C2)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)OC)C=CC1 YIYFDCRUODICCL-UHFFFAOYSA-N 0.000 claims 1
• NVHFJMHKOOLLKM-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC=2C=NC=CC2)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=NC=CC=C2)C=CC1 Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC=2C=NC=CC2)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=NC=CC=C2)C=CC1 NVHFJMHKOOLLKM-UHFFFAOYSA-N 0.000 claims 1
• JVQYWAHDGUOFBY-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCC)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCCCCC)C=CC1 Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCC)C=CC1.COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCCCCC)C=CC1 JVQYWAHDGUOFBY-UHFFFAOYSA-N 0.000 claims 1
• QHZVVQRKRBYLSB-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCCCCCC)C=CC1.OCCNC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCCCCCC)C=CC1.OCCNC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O QHZVVQRKRBYLSB-UHFFFAOYSA-N 0.000 claims 1
• VOQKHRIWSVHWHA-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCCCCCC)C=CC1.C(CCCCCC)NC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCCCCCC)C=CC1.C(CCCCCC)NC1CCN(CCC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O VOQKHRIWSVHWHA-UHFFFAOYSA-N 0.000 claims 1
• PVPNQAFQDUSQLR-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCN2CCOCC2)C=CC1.C12(CC3CC(CC(C1)C3)C2)CNC2CCN(CCC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O Chemical compound COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCN2CCOCC2)C=CC1.C12(CC3CC(CC(C1)C3)C2)CNC2CCN(CCC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O PVPNQAFQDUSQLR-UHFFFAOYSA-N 0.000 claims 1
• IWYPKSWRHZSURS-UHFFFAOYSA-N ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCC(CCCC)CC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCN2CCCCC2)C=C1 Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCC(CCCC)CC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCN2CCCCC2)C=C1 IWYPKSWRHZSURS-UHFFFAOYSA-N 0.000 claims 1
• DIXVLBAXLRZGER-UHFFFAOYSA-N ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCCCC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCCCCC)C=C1 Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCCCC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCCCCC)C=C1 DIXVLBAXLRZGER-UHFFFAOYSA-N 0.000 claims 1
• KBHIPXRXDQMZTG-UHFFFAOYSA-N ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCCCCCC)C=C1.C(CCCCC)NC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCCCCCC)C=C1.C(CCCCC)NC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O KBHIPXRXDQMZTG-UHFFFAOYSA-N 0.000 claims 1
• RGLBGVQSFFSJBM-UHFFFAOYSA-N ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CCC2)CNCCCCCC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CCC2)NCC2=CC=C(C=C2)C(F)(F)F)C=C1 Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CCC2)CNCCCCCC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CCC2)NCC2=CC=C(C=C2)C(F)(F)F)C=C1 RGLBGVQSFFSJBM-UHFFFAOYSA-N 0.000 claims 1
• QPCFRJZLWDHXTN-UHFFFAOYSA-N ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)OC2=CC=CC=C2)C=C1.C(C)(C)(C)C1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC=C(C=C2)Cl)=O)C=C1 Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)OC2=CC=CC=C2)C=C1.C(C)(C)(C)C1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC=C(C=C2)Cl)=O)C=C1 QPCFRJZLWDHXTN-UHFFFAOYSA-N 0.000 claims 1
• PNCOAQYUDNWYPY-UHFFFAOYSA-N ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCCCC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NC=2SC=CN2)C=C1 Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCCCCCC)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NC=2SC=CN2)C=C1 PNCOAQYUDNWYPY-UHFFFAOYSA-N 0.000 claims 1
• HXXNUSXZTYZSON-UHFFFAOYSA-N ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCN2CCCCC2)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCC2=NC=CC=C2)C=C1 Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCN2CCCCC2)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCCC2=NC=CC=C2)C=C1 HXXNUSXZTYZSON-UHFFFAOYSA-N 0.000 claims 1
• FWPNECYTHSNNCH-UHFFFAOYSA-N ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCC2CCCCC2)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCCCCCCCCCC)C=C1 Chemical compound ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCC2CCCCC2)C=C1.ClC1=CC=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CCC2)NCCCCCCCCCCCC)C=C1 FWPNECYTHSNNCH-UHFFFAOYSA-N 0.000 claims 1
• PSCVTLBOTZELNK-UHFFFAOYSA-N ClC1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1.C1(=C(C(=CC(=C1)C)C)CNC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O)C Chemical compound ClC1=CC=C(CNC2CCN(CC2)S(=O)(=O)C2=CC=C(S2)CNC(C2=CC(=CC=C2)OC)=O)C=C1.C1(=C(C(=CC(=C1)C)C)CNC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O)C PSCVTLBOTZELNK-UHFFFAOYSA-N 0.000 claims 1
• NARYVODOJDLSSH-UHFFFAOYSA-N N-[[5-[3-(2-cyclohexylethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C(C1=CC=CC=C1)(=O)NCC=1SC(=CC=1)S(=O)(=O)N1CC(CC1)NCCC1CCCCC1 NARYVODOJDLSSH-UHFFFAOYSA-N 0.000 claims 1
• IBWBEKHRKFFQBP-UHFFFAOYSA-N N-[[5-[4-(hexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-2-hydroxybenzamide 2-hydroxy-N-[[5-[4-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound OC1=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CCC(CC2)NCC2=CC=C(C=C2)C(F)(F)F)C=CC=C1.C(CCCCC)NC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=C(C=CC=C1)O)=O IBWBEKHRKFFQBP-UHFFFAOYSA-N 0.000 claims 1
• YZZDNLPXRLBIIV-UHFFFAOYSA-N N-[[5-[4-(hexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide N-[[5-[4-(3-imidazol-1-ylpropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C(CCCCC)NC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O.N1(C=NC=C1)CCCNC1CCN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O YZZDNLPXRLBIIV-UHFFFAOYSA-N 0.000 claims 1
• 208000006011 Stroke Diseases 0.000 claims 1
• 150000002148 esters Chemical class 0.000 claims 1
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
• QFCPRUXYKVLAQK-UHFFFAOYSA-N n-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1CNC1CCNCC1 QFCPRUXYKVLAQK-UHFFFAOYSA-N 0.000 claims 1
• HVEKJUAYPMGFDD-UHFFFAOYSA-N n-[[4-(trifluoromethyl)phenyl]methyl]ethanamine Chemical compound CCNCC1=CC=C(C(F)(F)F)C=C1 HVEKJUAYPMGFDD-UHFFFAOYSA-N 0.000 claims 1
• DURIDXXKDRXNAX-UHFFFAOYSA-N n-[[5-[4-(2-ethylhexylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide;n-[[5-[4-(3-imidazol-1-ylpropylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCC(CC)CCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1.COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)NCCCN2C=NC=C2)=C1 DURIDXXKDRXNAX-UHFFFAOYSA-N 0.000 claims 1
• 229960003966 nicotinamide Drugs 0.000 claims 1
• 239000011570 nicotinamide Substances 0.000 claims 1
• 210000001672 ovary Anatomy 0.000 claims 1
• 201000002528 pancreatic cancer Diseases 0.000 claims 1
• 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
• 150000001875 compounds Chemical class 0.000 description 114
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
• 239000000243 solution Substances 0.000 description 58
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
• 210000004027 cell Anatomy 0.000 description 44
• 238000000034 method Methods 0.000 description 38
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
• 238000006243 chemical reaction Methods 0.000 description 30
• 239000011541 reaction mixture Substances 0.000 description 30
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 27
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 27
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
• 230000004913 activation Effects 0.000 description 24
• 235000019439 ethyl acetate Nutrition 0.000 description 24
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
• 235000019341 magnesium sulphate Nutrition 0.000 description 22
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 22
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
• 241000894007 species Species 0.000 description 20
• 239000007787 solid Substances 0.000 description 19
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
• 230000005764 inhibitory process Effects 0.000 description 17
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
• 239000012267 brine Substances 0.000 description 16
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
• 238000005160 1H NMR spectroscopy Methods 0.000 description 15
• 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 15
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
• 102000000588 Interleukin-2 Human genes 0.000 description 14
• 108010002350 Interleukin-2 Proteins 0.000 description 14
• 102000043136 MAP kinase family Human genes 0.000 description 14
• 108091054455 MAP kinase family Proteins 0.000 description 14
• 102100023132 Transcription factor Jun Human genes 0.000 description 14
• 210000002569 neuron Anatomy 0.000 description 14
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
• 238000004458 analytical method Methods 0.000 description 13
• 125000006239 protecting group Chemical group 0.000 description 13
• 239000002904 solvent Substances 0.000 description 13
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 12
• 239000002158 endotoxin Substances 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• 108090000623 proteins and genes Proteins 0.000 description 12
• 235000017557 sodium bicarbonate Nutrition 0.000 description 12
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
• 102000004127 Cytokines Human genes 0.000 description 11
• 108090000695 Cytokines Proteins 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 150000001266 acyl halides Chemical class 0.000 description 11
• 238000013459 approach Methods 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• 229920006008 lipopolysaccharide Polymers 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
• 108091023040 Transcription factor Proteins 0.000 description 10
• 102000040945 Transcription factor Human genes 0.000 description 10
• 230000026731 phosphorylation Effects 0.000 description 10
• 238000006366 phosphorylation reaction Methods 0.000 description 10
• 230000008569 process Effects 0.000 description 10
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
• 238000005481 NMR spectroscopy Methods 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 239000003153 chemical reaction reagent Substances 0.000 description 9
• 150000002576 ketones Chemical class 0.000 description 9
• 239000002609 medium Substances 0.000 description 9
• 239000008194 pharmaceutical composition Substances 0.000 description 9
• GDKHKGCITPNDCG-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(hexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 GDKHKGCITPNDCG-UHFFFAOYSA-N 0.000 description 8
• 108010068304 MAP Kinase Kinase 4 Proteins 0.000 description 8
• 230000006907 apoptotic process Effects 0.000 description 8
• 150000003857 carboxamides Chemical class 0.000 description 8
• 230000030833 cell death Effects 0.000 description 8
• 238000010790 dilution Methods 0.000 description 8
• 239000012895 dilution Substances 0.000 description 8
• 201000010099 disease Diseases 0.000 description 8
• 238000009472 formulation Methods 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 102000004169 proteins and genes Human genes 0.000 description 8
• 239000007858 starting material Substances 0.000 description 8
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 7
• 239000012825 JNK inhibitor Substances 0.000 description 7
• 108060001084 Luciferase Proteins 0.000 description 7
• 239000005089 Luciferase Substances 0.000 description 7
• 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 7
• 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 7
• 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 7
• 235000011089 carbon dioxide Nutrition 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• 239000001963 growth medium Substances 0.000 description 7
• 230000002401 inhibitory effect Effects 0.000 description 7
• 239000002953 phosphate buffered saline Substances 0.000 description 7
• 229920000642 polymer Polymers 0.000 description 7
• 230000011664 signaling Effects 0.000 description 7
• 238000010561 standard procedure Methods 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 6
• YLHTUKZXHAJUID-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(pentylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(NCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 YLHTUKZXHAJUID-UHFFFAOYSA-N 0.000 description 6
• 102100023995 Beta-nerve growth factor Human genes 0.000 description 6
• 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• 241000699670 Mus sp. Species 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• 108010025020 Nerve Growth Factor Proteins 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• 210000001744 T-lymphocyte Anatomy 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 238000005859 coupling reaction Methods 0.000 description 6
• 239000013058 crude material Substances 0.000 description 6
• PZNLFFXOENCJNZ-UHFFFAOYSA-N ethyl 2-[4-(hexylamino)piperidin-1-yl]sulfonyl-5-[[(3-methoxybenzoyl)amino]methyl]thiophene-3-carboxylate Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C1=C(C(=O)OCC)C=C(CNC(=O)C=2C=C(OC)C=CC=2)S1 PZNLFFXOENCJNZ-UHFFFAOYSA-N 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• 210000000987 immune system Anatomy 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 230000014759 maintenance of location Effects 0.000 description 6
• 210000000653 nervous system Anatomy 0.000 description 6
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• 210000002222 superior cervical ganglion Anatomy 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 229930192474 thiophene Natural products 0.000 description 6
• 238000010626 work up procedure Methods 0.000 description 6
• CRHGHCURUYSQTN-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(pentylamino)methyl]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(CNCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 CRHGHCURUYSQTN-UHFFFAOYSA-N 0.000 description 5
• 241000699694 Gerbillinae Species 0.000 description 5
• 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 5
• 108060006687 MAP kinase kinase kinase Proteins 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 235000011054 acetic acid Nutrition 0.000 description 5
• 125000003342 alkenyl group Chemical group 0.000 description 5
• 125000000304 alkynyl group Chemical group 0.000 description 5
• 229910052786 argon Inorganic materials 0.000 description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
• 239000006285 cell suspension Substances 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 230000006378 damage Effects 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 210000001320 hippocampus Anatomy 0.000 description 5
• 230000002757 inflammatory effect Effects 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 235000019198 oils Nutrition 0.000 description 5
• 108090000765 processed proteins & peptides Proteins 0.000 description 5
• 230000010410 reperfusion Effects 0.000 description 5
• 230000019491 signal transduction Effects 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 230000035882 stress Effects 0.000 description 5
• 239000000758 substrate Substances 0.000 description 5
• 239000006228 supernatant Substances 0.000 description 5
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 4
• BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 4
• RBGDLYUEXLWQBZ-UHFFFAOYSA-N 2-chlorobenzamide Chemical compound NC(=O)C1=CC=CC=C1Cl RBGDLYUEXLWQBZ-UHFFFAOYSA-N 0.000 description 4
• JJZPDCGJRLWDQI-UHFFFAOYSA-N 2-oxo-n-[[5-(4-oxopiperidin-1-yl)sulfonylthiophen-2-yl]methyl]-1h-pyridine-3-carboxamide Chemical compound C=1C=CNC(=O)C=1C(=O)NCC(S1)=CC=C1S(=O)(=O)N1CCC(=O)CC1 JJZPDCGJRLWDQI-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• KOXQQQLFMXRMEB-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[hexyl(pyridin-2-ylmethyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1N(CCCCCC)CC1=CC=CC=N1 KOXQQQLFMXRMEB-UHFFFAOYSA-N 0.000 description 4
• HWAXMFYECKQLDX-UHFFFAOYSA-N 5-[[(4-chlorobenzoyl)amino]methyl]thiophene-2-sulfonyl chloride Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(Cl)(=O)=O)S1 HWAXMFYECKQLDX-UHFFFAOYSA-N 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 101710105206 C-Jun-amino-terminal kinase-interacting protein 1 Proteins 0.000 description 4
• 102100022291 C-Jun-amino-terminal kinase-interacting protein 1 Human genes 0.000 description 4
• 238000002965 ELISA Methods 0.000 description 4
• 102100039556 Galectin-4 Human genes 0.000 description 4
• 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 4
• 101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 description 4
• 101710166851 JNK-interacting protein 1 Proteins 0.000 description 4
• 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 4
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
• 241000242739 Renilla Species 0.000 description 4
• 150000003863 ammonium salts Chemical class 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 150000007942 carboxylates Chemical class 0.000 description 4
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
• 229960004132 diethyl ether Drugs 0.000 description 4
• 230000004069 differentiation Effects 0.000 description 4
• 239000012636 effector Substances 0.000 description 4
• 239000006260 foam Substances 0.000 description 4
• 239000003102 growth factor Substances 0.000 description 4
• 150000003840 hydrochlorides Chemical class 0.000 description 4
• 230000028709 inflammatory response Effects 0.000 description 4
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
• 238000001819 mass spectrum Methods 0.000 description 4
• JIJTXGSBFBOTAP-UHFFFAOYSA-N n-[[5-[4-(heptylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 JIJTXGSBFBOTAP-UHFFFAOYSA-N 0.000 description 4
• 150000003053 piperidines Chemical class 0.000 description 4
• 239000002243 precursor Substances 0.000 description 4
• 230000004044 response Effects 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 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
• 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 3
• CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical compound ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 3
• BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 3
• WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 3
• 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 208000032382 Ischaemic stroke Diseases 0.000 description 3
• 102000002569 MAP Kinase Kinase 4 Human genes 0.000 description 3
• 241000124008 Mammalia Species 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
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-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
• 108010029485 Protein Isoforms Proteins 0.000 description 3
• 102000001708 Protein Isoforms Human genes 0.000 description 3
• 102000001253 Protein Kinase Human genes 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 150000001263 acyl chlorides Chemical class 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 230000001640 apoptogenic effect Effects 0.000 description 3
• 230000001363 autoimmune Effects 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 238000004113 cell culture Methods 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
• 239000012230 colorless oil Substances 0.000 description 3
• MAMQLSRUHZSUEV-UHFFFAOYSA-N ethyl 5-[[(3-methoxybenzoyl)amino]methyl]-2-(4-oxopiperidin-1-yl)sulfonylthiophene-3-carboxylate Chemical compound S1C(S(=O)(=O)N2CCC(=O)CC2)=C(C(=O)OCC)C=C1CNC(=O)C1=CC=CC(OC)=C1 MAMQLSRUHZSUEV-UHFFFAOYSA-N 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 239000012894 fetal calf serum Substances 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 230000001939 inductive effect Effects 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 238000004020 luminiscence type Methods 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 230000016273 neuron death Effects 0.000 description 3
• 230000009223 neuronal apoptosis Effects 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 102000004196 processed proteins & peptides Human genes 0.000 description 3
• 108060006633 protein kinase Proteins 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 229920005989 resin Polymers 0.000 description 3
• 239000011347 resin Substances 0.000 description 3
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 238000006277 sulfonation reaction Methods 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 230000002889 sympathetic effect Effects 0.000 description 3
• FKKJJPMGAWGYPN-UHFFFAOYSA-N thiophen-2-ylmethanamine Chemical compound NCC1=CC=CS1 FKKJJPMGAWGYPN-UHFFFAOYSA-N 0.000 description 3
• 238000001890 transfection Methods 0.000 description 3
• 238000011144 upstream manufacturing Methods 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
• KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
• CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 2
• SCMQZCDHXKMJJQ-UHFFFAOYSA-N 3-[[(3-methoxybenzoyl)amino]methyl]thiophene-2-sulfonyl chloride Chemical compound COC1=CC=CC(C(=O)NCC2=C(SC=C2)S(Cl)(=O)=O)=C1 SCMQZCDHXKMJJQ-UHFFFAOYSA-N 0.000 description 2
• GDZMSRFBYYKGIN-UHFFFAOYSA-N 3-methoxy-n-[[5-(4-oxoazepan-1-yl)sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(=O)CCC2)=C1 GDZMSRFBYYKGIN-UHFFFAOYSA-N 0.000 description 2
• RUQIUASLAXJZIE-UHFFFAOYSA-N 3-methoxybenzoyl chloride Chemical compound COC1=CC=CC(C(Cl)=O)=C1 RUQIUASLAXJZIE-UHFFFAOYSA-N 0.000 description 2
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
• OPXTXCLTXQNTQH-UHFFFAOYSA-N 4-chloro-n-(thiophen-2-ylmethyl)benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=CS1 OPXTXCLTXQNTQH-UHFFFAOYSA-N 0.000 description 2
• YXYZWXRBHIBALW-UHFFFAOYSA-N 4-chloro-n-[[5-(4-oxopiperidin-1-yl)sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(=O)CC2)S1 YXYZWXRBHIBALW-UHFFFAOYSA-N 0.000 description 2
• XHGDOYAFJXNKQC-CYBMUJFWSA-N 4-chloro-n-[[5-[(3r)-3-hydroxypyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1[C@H](O)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 XHGDOYAFJXNKQC-CYBMUJFWSA-N 0.000 description 2
• RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 2
• WDGGZSSZDYAHCF-UHFFFAOYSA-M 5-[[(3-methoxybenzoyl)amino]methyl]thiophene-2-sulfonate;tetrabutylazanium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC.COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S([O-])(=O)=O)=C1 WDGGZSSZDYAHCF-UHFFFAOYSA-M 0.000 description 2
• RTSXKBQXXIFLKN-UHFFFAOYSA-N 5-[[bis(prop-2-enyl)amino]methyl]thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(CN(CC=C)CC=C)S1 RTSXKBQXXIFLKN-UHFFFAOYSA-N 0.000 description 2
• KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 206010010904 Convulsion Diseases 0.000 description 2
• 108020004414 DNA Proteins 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• 102100023332 Dual specificity mitogen-activated protein kinase kinase 7 Human genes 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 238000012286 ELISA Assay Methods 0.000 description 2
• 206010019280 Heart failures Diseases 0.000 description 2
• 208000016988 Hemorrhagic Stroke Diseases 0.000 description 2
• 101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 Proteins 0.000 description 2
• 101000624594 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 7 Proteins 0.000 description 2
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
• 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 2
• 206010021143 Hypoxia Diseases 0.000 description 2
• 108010074328 Interferon-gamma Proteins 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 102000005741 Metalloproteases Human genes 0.000 description 2
• 108010006035 Metalloproteases Proteins 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 108091008874 T cell receptors Proteins 0.000 description 2
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
• 210000004241 Th2 cell Anatomy 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 150000003973 alkyl amines Chemical class 0.000 description 2
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
• 150000001409 amidines Chemical class 0.000 description 2
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 210000000612 antigen-presenting cell Anatomy 0.000 description 2
• 230000007503 antigenic stimulation Effects 0.000 description 2
• 238000003782 apoptosis assay Methods 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000001743 benzylic group Chemical group 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 210000000988 bone and bone Anatomy 0.000 description 2
• 150000001728 carbonyl compounds Chemical class 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 210000000845 cartilage Anatomy 0.000 description 2
• 239000013553 cell monolayer Substances 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 230000003833 cell viability Effects 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 230000002490 cerebral effect Effects 0.000 description 2
• 229910052681 coesite Inorganic materials 0.000 description 2
• 229910052906 cristobalite Inorganic materials 0.000 description 2
• KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 2
• BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
• 239000000539 dimer Substances 0.000 description 2
• 230000003828 downregulation Effects 0.000 description 2
• 238000010864 dual luciferase reporter gene assay Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• PPNWPZYLTRSUMN-UHFFFAOYSA-N ethyl 2-(1,4-dioxa-8-azaspiro[4.5]decan-8-ylsulfonyl)-5-[[(3-methoxybenzoyl)amino]methyl]thiophene-3-carboxylate Chemical compound S1C(S(=O)(=O)N2CCC3(CC2)OCCO3)=C(C(=O)OCC)C=C1CNC(=O)C1=CC=CC(OC)=C1 PPNWPZYLTRSUMN-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 230000003492 excitotoxic effect Effects 0.000 description 2
• 231100000063 excitotoxicity Toxicity 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 239000012467 final product Substances 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 235000019264 food flavour enhancer Nutrition 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
• 150000002374 hemiaminals Chemical class 0.000 description 2
• JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 230000007954 hypoxia Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 239000012442 inert solvent Substances 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 2
• PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 2
• QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
• 239000007791 liquid phase Substances 0.000 description 2
• 208000019423 liver disease Diseases 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 210000004962 mammalian cell Anatomy 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• WPWFBRXWLVRKRG-UHFFFAOYSA-N n-[[5-[4-[[amino-[4-(trifluoromethyl)phenyl]methylidene]amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=N)NC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 WPWFBRXWLVRKRG-UHFFFAOYSA-N 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 239000013642 negative control Substances 0.000 description 2
• 210000005036 nerve Anatomy 0.000 description 2
• 231100000590 oncogenic Toxicity 0.000 description 2
• 230000002246 oncogenic effect Effects 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
• LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 2
• FLKRMXAWABTWSH-UHFFFAOYSA-N piperidine-1-sulfonamide Chemical class NS(=O)(=O)N1CCCCC1 FLKRMXAWABTWSH-UHFFFAOYSA-N 0.000 description 2
• 229920001184 polypeptide Polymers 0.000 description 2
• 229920000136 polysorbate Polymers 0.000 description 2
• 235000015320 potassium carbonate Nutrition 0.000 description 2
• 230000005522 programmed cell death Effects 0.000 description 2
• 230000000770 proinflammatory effect Effects 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 238000011084 recovery Methods 0.000 description 2
• 208000037803 restenosis Diseases 0.000 description 2
• 238000006798 ring closing metathesis reaction Methods 0.000 description 2
• 230000035939 shock Effects 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 235000012239 silicon dioxide Nutrition 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 229910052682 stishovite Inorganic materials 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
• 150000003871 sulfonates Chemical class 0.000 description 2
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 2
• 229910052905 tridymite Inorganic materials 0.000 description 2
• 230000001960 triggered effect Effects 0.000 description 2
• 125000004953 trihalomethyl group Chemical group 0.000 description 2
• 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 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 229910052727 yttrium Inorganic materials 0.000 description 2
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• VXLPFTSOFKGDHB-IJHRGXPZSA-N (2s)-1-[5-[[(4-chlorobenzoyl)amino]methyl]thiophen-2-yl]sulfonyl-4-(hexylamino)pyrrolidine-2-carboxylic acid Chemical compound C1C(NCCCCCC)C[C@@H](C(O)=O)N1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 VXLPFTSOFKGDHB-IJHRGXPZSA-N 0.000 description 1
• GRRNUXAQVGOGFE-XKIAHZFYSA-N (2s,3'r,3as,4s,4's,5'r,6r,6'r,7s,7as)-4-[(1r,2s,3r,5s,6r)-3-amino-2,6-dihydroxy-5-(methylamino)cyclohexyl]oxy-6'-[(1r)-1-amino-2-hydroxyethyl]-6-(hydroxymethyl)spiro[4,6,7,7a-tetrahydro-3ah-[1,3]dioxolo[4,5-c]pyran-2,2'-oxane]-3',4',5',7-tetrol Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H]([C@H](N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-XKIAHZFYSA-N 0.000 description 1
• LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• VVSASNKOFCZVES-UHFFFAOYSA-N 1,3-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)N(C)C1=O VVSASNKOFCZVES-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• 238000004293 19F NMR spectroscopy Methods 0.000 description 1
• PYHXGXCGESYPCW-UHFFFAOYSA-M 2,2-diphenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)[O-])C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-M 0.000 description 1
• MXIUWSYTQJLIKE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC=C1C(Cl)=O MXIUWSYTQJLIKE-UHFFFAOYSA-N 0.000 description 1
• UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 description 1
• KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• PXQTZKZWTYRZQL-UHFFFAOYSA-N 2-hydroxy-n-[[5-[4-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound OC1=CC=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)C(F)(F)F)S1 PXQTZKZWTYRZQL-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• YFPMKTSZVUDZDO-UHFFFAOYSA-N 2-propoxyacetaldehyde Chemical compound CCCOCC=O YFPMKTSZVUDZDO-UHFFFAOYSA-N 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• XPYOORHZRLSTSG-UHFFFAOYSA-N 2-sulfonylpiperidine Chemical class O=S(=O)=C1CCCCN1 XPYOORHZRLSTSG-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
• RCPZMRMSIOJNEK-UHFFFAOYSA-N 3-methoxy-n-(thiophen-2-ylmethyl)benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC=CC=2)=C1 RCPZMRMSIOJNEK-UHFFFAOYSA-N 0.000 description 1
• MAHSHMCCJZUSIB-UHFFFAOYSA-N 3-methoxy-n-[[5-[3-(2-piperidin-1-ylethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CC(CC2)NCCN2CCCCC2)=C1 MAHSHMCCJZUSIB-UHFFFAOYSA-N 0.000 description 1
• DLHZIDXNHZXNCG-UHFFFAOYSA-N 3-methoxy-n-[[5-[3-(2-propoxyethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(NCCOCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 DLHZIDXNHZXNCG-UHFFFAOYSA-N 0.000 description 1
• FQWANLJPEMLYKA-UHFFFAOYSA-N 3-methoxy-n-[[5-[3-(octylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(NCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 FQWANLJPEMLYKA-UHFFFAOYSA-N 0.000 description 1
• WBWRBQJQTXJQEH-UHFFFAOYSA-N 3-methoxy-n-[[5-[3-(pentylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(NCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 WBWRBQJQTXJQEH-UHFFFAOYSA-N 0.000 description 1
• BQOPCSNIKARECX-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(2-phenylpropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC(C)C=2C=CC=CC=2)=C1 BQOPCSNIKARECX-UHFFFAOYSA-N 0.000 description 1
• KITQPGQJYRKLSF-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(2-piperidin-1-ylethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)NCCN2CCCCC2)=C1 KITQPGQJYRKLSF-UHFFFAOYSA-N 0.000 description 1
• GFJRJIKLSAEMNY-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(2-piperidin-1-ylethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCN2CCCCC2)=C1 GFJRJIKLSAEMNY-UHFFFAOYSA-N 0.000 description 1
• KZSNDEFQVGXPMZ-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(2-propoxyethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCOCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 KZSNDEFQVGXPMZ-UHFFFAOYSA-N 0.000 description 1
• WCEKCURXOZTGDS-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(2-propoxyethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCOCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 WCEKCURXOZTGDS-UHFFFAOYSA-N 0.000 description 1
• YSUDSBJJPCPFPT-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(2-thiophen-2-ylethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCC=2SC=CC=2)=C1 YSUDSBJJPCPFPT-UHFFFAOYSA-N 0.000 description 1
• VJNFCXZOALNNPM-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(3-morpholin-4-ylpropylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)NCCCN2CCOCC2)=C1 VJNFCXZOALNNPM-UHFFFAOYSA-N 0.000 description 1
• RNZCQBIJDLAFHR-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(3-phenylpropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCCC=2C=CC=CC=2)=C1 RNZCQBIJDLAFHR-UHFFFAOYSA-N 0.000 description 1
• QHMAVLYJDMGCEA-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(naphthalen-1-ylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C3=CC=CC=C3C=CC=2)=C1 QHMAVLYJDMGCEA-UHFFFAOYSA-N 0.000 description 1
• JDDCXMNNTRBYBN-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(nonylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 JDDCXMNNTRBYBN-UHFFFAOYSA-N 0.000 description 1
• YDCCBDNEFUXAFX-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(octylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 YDCCBDNEFUXAFX-UHFFFAOYSA-N 0.000 description 1
• SRVHDHVRVFJPEC-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(octylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 SRVHDHVRVFJPEC-UHFFFAOYSA-N 0.000 description 1
• YWQNBWKSGSHTSA-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(pentylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 YWQNBWKSGSHTSA-UHFFFAOYSA-N 0.000 description 1
• GJDJWHWZYXRUFL-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(pentylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 GJDJWHWZYXRUFL-UHFFFAOYSA-N 0.000 description 1
• VKHNIKHUZIDBIF-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(pyridin-2-ylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2N=CC=CC=2)=C1 VKHNIKHUZIDBIF-UHFFFAOYSA-N 0.000 description 1
• KNBKWCCNNOOXPL-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(pyridin-3-ylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=NC=CC=2)=C1 KNBKWCCNNOOXPL-UHFFFAOYSA-N 0.000 description 1
• WMJNMYNGCZXGIA-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(pyridin-4-ylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CN=CC=2)=C1 WMJNMYNGCZXGIA-UHFFFAOYSA-N 0.000 description 1
• DOBMKOAVENARPA-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-(quinolin-4-ylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C3=CC=CC=C3N=CC=2)=C1 DOBMKOAVENARPA-UHFFFAOYSA-N 0.000 description 1
• IMQRFPBEONZCPF-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(2,4,6-trimethylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C(=CC(C)=CC=2C)C)=C1 IMQRFPBEONZCPF-UHFFFAOYSA-N 0.000 description 1
• MNVLEGMIVINXKM-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(3-methylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=C(C)C=CC=2)=C1 MNVLEGMIVINXKM-UHFFFAOYSA-N 0.000 description 1
• BLJVWTGKRFCVBZ-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(3-phenylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=C(C=CC=2)C=2C=CC=CC=2)=C1 BLJVWTGKRFCVBZ-UHFFFAOYSA-N 0.000 description 1
• SZBHMBJTXNIGQH-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-methoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(OC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 SZBHMBJTXNIGQH-UHFFFAOYSA-N 0.000 description 1
• XNKMZWSHDVMLSI-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-pentylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(CCCCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 XNKMZWSHDVMLSI-UHFFFAOYSA-N 0.000 description 1
• CHWPJAXADOPKIO-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-phenylmethoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1 CHWPJAXADOPKIO-UHFFFAOYSA-N 0.000 description 1
• AZGRWGCJEDGBIZ-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-phenylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 AZGRWGCJEDGBIZ-UHFFFAOYSA-N 0.000 description 1
• GYBHJPHJSXIXCZ-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-propan-2-ylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)C(C)C)=C1 GYBHJPHJSXIXCZ-UHFFFAOYSA-N 0.000 description 1
• SVSUWZYJFOYRFK-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[(4-propylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(CCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 SVSUWZYJFOYRFK-UHFFFAOYSA-N 0.000 description 1
• OTQSQGVTQLVRQH-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[2-(4-phenylphenyl)ethylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCC=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 OTQSQGVTQLVRQH-UHFFFAOYSA-N 0.000 description 1
• ZXRIHWPEXPLNNC-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[2-[3-(trifluoromethyl)phenyl]ethylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCC=2C=C(C=CC=2)C(F)(F)F)=C1 ZXRIHWPEXPLNNC-UHFFFAOYSA-N 0.000 description 1
• NONOZHXFYAEZEL-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[2-[4-(trifluoromethyl)phenyl]propan-2-ylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NC(C)(C)C=2C=CC(=CC=2)C(F)(F)F)=C1 NONOZHXFYAEZEL-UHFFFAOYSA-N 0.000 description 1
• MEJQSJZFHPABOL-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[4-(2-methylpropyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(CC(C)C)=CC=2)=C1 MEJQSJZFHPABOL-UHFFFAOYSA-N 0.000 description 1
• NLFQFVHCCRNBQW-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[4-(trifluoromethoxy)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(OC(F)(F)F)=CC=2)=C1 NLFQFVHCCRNBQW-UHFFFAOYSA-N 0.000 description 1
• SUKHVBVIZFJHOI-UHFFFAOYSA-N 3-methoxy-n-[[5-[4-[[4-(trifluoromethylsulfonyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)S(=O)(=O)C(F)(F)F)=C1 SUKHVBVIZFJHOI-UHFFFAOYSA-N 0.000 description 1
• VKPLPDIMEREJJF-UHFFFAOYSA-N 3-methoxybenzamide Chemical compound COC1=CC=CC(C(N)=O)=C1 VKPLPDIMEREJJF-UHFFFAOYSA-N 0.000 description 1
• DRNJIKRLQJRKMM-UHFFFAOYSA-N 4-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=C(C#N)C=C1 DRNJIKRLQJRKMM-UHFFFAOYSA-N 0.000 description 1
• YMMNSNFRGFKVMR-UHFFFAOYSA-N 4-chloro-n-[[5-(3-oxopyrrolidin-1-yl)sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CC(=O)CC2)S1 YMMNSNFRGFKVMR-UHFFFAOYSA-N 0.000 description 1
• BUVCQNQBGZLGAH-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(2-cyclohexylethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CC(CC2)NCCC2CCCCC2)S1 BUVCQNQBGZLGAH-UHFFFAOYSA-N 0.000 description 1
• RWDUGBMWCMDUHQ-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(2-ethylhexylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(NCC(CC)CCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 RWDUGBMWCMDUHQ-UHFFFAOYSA-N 0.000 description 1
• BRWJFVYFRSUCHH-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(2-piperidin-1-ylethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CC(CC2)NCCN2CCCCC2)S1 BRWJFVYFRSUCHH-UHFFFAOYSA-N 0.000 description 1
• TWGRXZOAOXCLGZ-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(3-morpholin-4-ylpropylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CC(CC2)NCCCN2CCOCC2)S1 TWGRXZOAOXCLGZ-UHFFFAOYSA-N 0.000 description 1
• HCRATRDKMYDJDC-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(heptylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(NCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 HCRATRDKMYDJDC-UHFFFAOYSA-N 0.000 description 1
• XGIHWZNNOKUWDJ-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(hexylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(NCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 XGIHWZNNOKUWDJ-UHFFFAOYSA-N 0.000 description 1
• RCVFSEZGFQCOBD-UHFFFAOYSA-N 4-chloro-n-[[5-[3-(octylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(NCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 RCVFSEZGFQCOBD-UHFFFAOYSA-N 0.000 description 1
• RQYKEGAQMFXVJP-UHFFFAOYSA-N 4-chloro-n-[[5-[3-[(hexylamino)methyl]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1C(CNCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 RQYKEGAQMFXVJP-UHFFFAOYSA-N 0.000 description 1
• KWYJOFXOFWATEF-UHFFFAOYSA-N 4-chloro-n-[[5-[3-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNC1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1 KWYJOFXOFWATEF-UHFFFAOYSA-N 0.000 description 1
• GVHIWUGNPXBCTB-UHFFFAOYSA-N 4-chloro-n-[[5-[3-[[4-(trifluoromethyl)phenyl]methylamino]pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNC1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 GVHIWUGNPXBCTB-UHFFFAOYSA-N 0.000 description 1
• GDBCHABFFBVTAC-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(1,3-thiazol-2-ylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NC=2SC=CN=2)S1 GDBCHABFFBVTAC-UHFFFAOYSA-N 0.000 description 1
• CIIIXBGYIXZJBT-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-cyclohexylethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CCC2)NCCC2CCCCC2)S1 CIIIXBGYIXZJBT-UHFFFAOYSA-N 0.000 description 1
• SDEYCKRAIPMKHJ-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-cyclohexylethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCCC2CCCCC2)S1 SDEYCKRAIPMKHJ-UHFFFAOYSA-N 0.000 description 1
• ZEQTWQWSSSUDKV-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-ethylhexylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCC(CC)CCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 ZEQTWQWSSSUDKV-UHFFFAOYSA-N 0.000 description 1
• JHKPLVAAQGLEPX-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-ethylhexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCC(CC)CCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 JHKPLVAAQGLEPX-UHFFFAOYSA-N 0.000 description 1
• TVJRQTSPMZXFGB-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-piperidin-1-ylethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCCN2CCCCC2)S1 TVJRQTSPMZXFGB-UHFFFAOYSA-N 0.000 description 1
• LUMJMSMVXOTWCT-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-propoxyethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCOCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 LUMJMSMVXOTWCT-UHFFFAOYSA-N 0.000 description 1
• CYPFWIUNFVXBTR-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-propoxyethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCOCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 CYPFWIUNFVXBTR-UHFFFAOYSA-N 0.000 description 1
• RGPOBKHHKYZHGO-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(2-pyridin-2-ylethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCCC=2N=CC=CC=2)S1 RGPOBKHHKYZHGO-UHFFFAOYSA-N 0.000 description 1
• BOKQMLSFAHQVJD-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(3-imidazol-1-ylpropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCCCN2C=NC=C2)S1 BOKQMLSFAHQVJD-UHFFFAOYSA-N 0.000 description 1
• FRIAPOLWMNLJOE-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(cyclohexylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCC2CCCCC2)S1 FRIAPOLWMNLJOE-UHFFFAOYSA-N 0.000 description 1
• PILHIILMXFXEGP-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(dodecylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 PILHIILMXFXEGP-UHFFFAOYSA-N 0.000 description 1
• FWXPQNAYNFBQIC-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(dodecylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 FWXPQNAYNFBQIC-UHFFFAOYSA-N 0.000 description 1
• BRLVCXYGWOZEPV-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(heptylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 BRLVCXYGWOZEPV-UHFFFAOYSA-N 0.000 description 1
• GQGVRCYFYVRTED-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(heptylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 GQGVRCYFYVRTED-UHFFFAOYSA-N 0.000 description 1
• RVLKWOOHJIBGHR-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(hexylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 RVLKWOOHJIBGHR-UHFFFAOYSA-N 0.000 description 1
• OPYRLNCUCPAIPQ-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(octylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 OPYRLNCUCPAIPQ-UHFFFAOYSA-N 0.000 description 1
• OHDMVTBELZFHAK-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(octylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 OHDMVTBELZFHAK-UHFFFAOYSA-N 0.000 description 1
• DMSSOIOIUWCVDY-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(pentylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 DMSSOIOIUWCVDY-UHFFFAOYSA-N 0.000 description 1
• FVIMGKFAIXLCRU-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(pentylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 FVIMGKFAIXLCRU-UHFFFAOYSA-N 0.000 description 1
• ZVUVHRYRAGSAOI-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(propylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 ZVUVHRYRAGSAOI-UHFFFAOYSA-N 0.000 description 1
• GETINMRFKPZTMI-UHFFFAOYSA-N 4-chloro-n-[[5-[4-(quinolin-4-ylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCC=2C3=CC=CC=C3N=CC=2)S1 GETINMRFKPZTMI-UHFFFAOYSA-N 0.000 description 1
• MDIOJCXOEWWVOD-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[(3,4-dihydroxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=C(O)C(O)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 MDIOJCXOEWWVOD-UHFFFAOYSA-N 0.000 description 1
• ZZIHVCCGSDQAAC-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[(3-chlorophenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCC=2C=C(Cl)C=CC=2)S1 ZZIHVCCGSDQAAC-UHFFFAOYSA-N 0.000 description 1
• AVYCTEZUZHQYLR-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[(4-phenoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCC=2C=CC(OC=3C=CC=CC=3)=CC=2)S1 AVYCTEZUZHQYLR-UHFFFAOYSA-N 0.000 description 1
• FFTMEKVATSLZAW-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[(4-propoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(OCCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 FFTMEKVATSLZAW-UHFFFAOYSA-N 0.000 description 1
• QSHNSFUKEJXNCG-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[2-(trifluoromethylsulfonylamino)ethylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(NCCNS(=O)(=O)C(F)(F)F)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 QSHNSFUKEJXNCG-UHFFFAOYSA-N 0.000 description 1
• SCPWZCWDIIFELZ-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[[4-(difluoromethoxy)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(OC(F)F)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 SCPWZCWDIIFELZ-UHFFFAOYSA-N 0.000 description 1
• RHDAZTUTKLAUNI-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[[4-(trifluoromethylsulfonyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 RHDAZTUTKLAUNI-UHFFFAOYSA-N 0.000 description 1
• RKWXQGKEUVKRGE-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[cyclohexylmethyl(hexyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1N(CCCCCC)CC1CCCCC1 RKWXQGKEUVKRGE-UHFFFAOYSA-N 0.000 description 1
• DYSCUYNFHSVFSU-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[hexyl(2-phenylethyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1N(CCCCCC)CCC1=CC=CC=C1 DYSCUYNFHSVFSU-UHFFFAOYSA-N 0.000 description 1
• OCTZCSIXSFPNEQ-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[hexyl(methyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CC(N(C)CCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 OCTZCSIXSFPNEQ-UHFFFAOYSA-N 0.000 description 1
• QDOJFSKGVDWIHV-UHFFFAOYSA-N 4-chloro-n-[[5-[4-[hexyl(pyridin-3-ylmethyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1N(CCCCCC)CC1=CC=CN=C1 QDOJFSKGVDWIHV-UHFFFAOYSA-N 0.000 description 1
• DBMFYTQPPBBKHI-UHFFFAOYSA-N 4-cyanobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(C#N)C=C1 DBMFYTQPPBBKHI-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
• SMISIQMCBPTDKU-UHFFFAOYSA-N 5-[[(3-methoxybenzoyl)amino]methyl]thiophene-2-sulfonyl chloride Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(Cl)(=O)=O)=C1 SMISIQMCBPTDKU-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 description 1
• 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 230000003844 B-cell-activation Effects 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 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
• YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
• 238000011740 C57BL/6 mouse Methods 0.000 description 1
• 101100026251 Caenorhabditis elegans atf-2 gene Proteins 0.000 description 1
• 101100513486 Caenorhabditis elegans mkk-4 gene Proteins 0.000 description 1
• 101100476202 Caenorhabditis elegans mog-2 gene Proteins 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 206010007559 Cardiac failure congestive Diseases 0.000 description 1
• 206010048964 Carotid artery occlusion Diseases 0.000 description 1
• 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
• 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 101710150820 Cellular tumor antigen p53 Proteins 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 108010077544 Chromatin Proteins 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 206010010144 Completed suicide Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229920000742 Cotton Polymers 0.000 description 1
• 102100023033 Cyclic AMP-dependent transcription factor ATF-2 Human genes 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 230000004568 DNA-binding Effects 0.000 description 1
• 102000010170 Death domains Human genes 0.000 description 1
• 108050001718 Death domains Proteins 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• 239000004097 EU approved flavor enhancer Substances 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 239000001263 FEMA 3042 Substances 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 208000010496 Heart Arrest Diseases 0.000 description 1
• 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 1
• 101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 description 1
• 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
• 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 102100037850 Interferon gamma Human genes 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 102000003777 Interleukin-1 beta Human genes 0.000 description 1
• 108090000193 Interleukin-1 beta Proteins 0.000 description 1
• 108090000174 Interleukin-10 Proteins 0.000 description 1
• 108090000176 Interleukin-13 Proteins 0.000 description 1
• 108090000978 Interleukin-4 Proteins 0.000 description 1
• 108010002616 Interleukin-5 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 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
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
• 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
• 108010075654 MAP Kinase Kinase Kinase 1 Proteins 0.000 description 1
• 244000246386 Mentha pulegium Species 0.000 description 1
• 235000016257 Mentha pulegium Nutrition 0.000 description 1
• 235000004357 Mentha x piperita Nutrition 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• 102000047918 Myelin Basic Human genes 0.000 description 1
• 101710107068 Myelin basic protein Proteins 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
• 206010056677 Nerve degeneration Diseases 0.000 description 1
• 208000028389 Nerve injury Diseases 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000037273 Pathologic Processes Diseases 0.000 description 1
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 1
• 229920002230 Pectic acid Polymers 0.000 description 1
• LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
• 206010057249 Phagocytosis Diseases 0.000 description 1
• 108010020346 Polyglutamic Acid Proteins 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 102100027584 Protein c-Fos Human genes 0.000 description 1
• 108010018070 Proto-Oncogene Proteins c-ets Proteins 0.000 description 1
• 102000004053 Proto-Oncogene Proteins c-ets Human genes 0.000 description 1
• 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 229910006024 SO2Cl2 Inorganic materials 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 230000006044 T cell activation Effects 0.000 description 1
• 208000000389 T-cell leukemia Diseases 0.000 description 1
• 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
• 230000029662 T-helper 1 type immune response Effects 0.000 description 1
• 239000012317 TBTU Substances 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 210000000447 Th1 cell Anatomy 0.000 description 1
• YGZWVPBHYABGLT-KJEVXHAQSA-N Thr-Pro-Tyr Chemical group C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 YGZWVPBHYABGLT-KJEVXHAQSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 208000030886 Traumatic Brain injury Diseases 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• PRDBLLIPPDOICK-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=C(C(F)(F)F)C=C1 PRDBLLIPPDOICK-UHFFFAOYSA-N 0.000 description 1
• ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 1
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 125000002877 alkyl aryl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000007854 aminals Chemical class 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 208000021328 arterial occlusion Diseases 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 230000000923 atherogenic effect Effects 0.000 description 1
• 230000003143 atherosclerotic effect Effects 0.000 description 1
• 230000006472 autoimmune response Effects 0.000 description 1
• GMHPWGYTSXHHPI-UHFFFAOYSA-N azepan-4-one Chemical compound O=C1CCCNCC1 GMHPWGYTSXHHPI-UHFFFAOYSA-N 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 150000003935 benzaldehydes Chemical class 0.000 description 1
• 229940054066 benzamide antipsychotics Drugs 0.000 description 1
• 150000003936 benzamides Chemical class 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 230000002146 bilateral effect Effects 0.000 description 1
• 230000027455 binding Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 230000005978 brain dysfunction 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
• 230000005587 bubbling Effects 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 244000309464 bull Species 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
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 210000001715 carotid artery Anatomy 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000012292 cell migration Effects 0.000 description 1
• 210000003855 cell nucleus Anatomy 0.000 description 1
• 230000010307 cell transformation Effects 0.000 description 1
• 230000004637 cellular stress Effects 0.000 description 1
• 229940106189 ceramide Drugs 0.000 description 1
• ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
• 206010008118 cerebral infarction Diseases 0.000 description 1
• 239000013626 chemical specie Substances 0.000 description 1
• 239000012320 chlorinating reagent Substances 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• 238000005957 chlorosulfonylation reaction Methods 0.000 description 1
• 210000003483 chromatin Anatomy 0.000 description 1
• JOPOVCBBYLSVDA-UHFFFAOYSA-N chromium(6+) Chemical class [Cr+6] JOPOVCBBYLSVDA-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid Chemical compound OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 238000012937 correction Methods 0.000 description 1
• 230000004940 costimulation Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000005520 cutting process Methods 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000000593 degrading effect Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 229910000397 disodium phosphate Inorganic materials 0.000 description 1
• 235000019800 disodium phosphate Nutrition 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 210000003162 effector t lymphocyte Anatomy 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000001037 epileptic effect Effects 0.000 description 1
• 230000003628 erosive effect Effects 0.000 description 1
• OMOQNWFNWBKNDA-UHFFFAOYSA-N ethyl 5-[[(3-methoxybenzoyl)amino]methyl]-2-[4-[[4-(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophene-3-carboxylate Chemical compound S1C(S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)C(F)(F)F)=C(C(=O)OCC)C=C1CNC(=O)C1=CC=CC(OC)=C1 OMOQNWFNWBKNDA-UHFFFAOYSA-N 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000013265 extended release Methods 0.000 description 1
• 230000006355 external stress Effects 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• JFSPBVWPKOEZCB-UHFFFAOYSA-N fenfuram Chemical compound O1C=CC(C(=O)NC=2C=CC=CC=2)=C1C JFSPBVWPKOEZCB-UHFFFAOYSA-N 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
• 239000012634 fragment Substances 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• CATSNJVOTSVZJV-UHFFFAOYSA-N heptan-2-one Chemical compound CCCCCC(C)=O CATSNJVOTSVZJV-UHFFFAOYSA-N 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 235000001050 hortel pimenta Nutrition 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 1
• 125000001165 hydrophobic group Chemical group 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 229940097277 hygromycin b Drugs 0.000 description 1
• 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 229960003130 interferon gamma Drugs 0.000 description 1
• 230000004073 interleukin-2 production Effects 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000005990 isobenzothienyl group Chemical group 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 239000012948 isocyanate Substances 0.000 description 1
• 150000002513 isocyanates Chemical class 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
• 229950006874 kainic acid Drugs 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 230000002147 killing effect Effects 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
• 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 235000012054 meals Nutrition 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 238000006263 metalation reaction Methods 0.000 description 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• MYMHRAOVLXQTBG-QWAKEFERSA-N methyl (2s)-1-[5-[[(4-chlorobenzoyl)amino]methyl]thiophen-2-yl]sulfonyl-4-(hexylamino)pyrrolidine-2-carboxylate Chemical compound C1C(NCCCCCC)C[C@@H](C(=O)OC)N1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 MYMHRAOVLXQTBG-QWAKEFERSA-N 0.000 description 1
• SAAUDOGTWMFFHD-UHFFFAOYSA-N methyl 2-[[1-[5-[[(4-chlorobenzoyl)amino]methyl]thiophen-2-yl]sulfonylpiperidin-4-yl]-hexylamino]acetate Chemical compound C1CC(N(CC(=O)OC)CCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 SAAUDOGTWMFFHD-UHFFFAOYSA-N 0.000 description 1
• 229960001047 methyl salicylate Drugs 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000002297 mitogenic effect Effects 0.000 description 1
• 230000004660 morphological change Effects 0.000 description 1
• QKMJVIBQNUDLOS-UHFFFAOYSA-N n-[[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-ylsulfonyl)thiophen-2-yl]methyl]-2-oxo-1h-pyridine-3-carboxamide Chemical compound C=1C=CNC(=O)C=1C(=O)NCC(S1)=CC=C1S(=O)(=O)N(CC1)CCC21OCCO2 QKMJVIBQNUDLOS-UHFFFAOYSA-N 0.000 description 1
• QTHHMMWIZXYCCX-UHFFFAOYSA-N n-[[5-[3-(2-ethylhexylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1C(NCC(CC)CCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 QTHHMMWIZXYCCX-UHFFFAOYSA-N 0.000 description 1
• YWVUEWMXOUVOQS-UHFFFAOYSA-N n-[[5-[3-(butylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1C(NCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 YWVUEWMXOUVOQS-UHFFFAOYSA-N 0.000 description 1
• SERLGPIXTTUKMR-UHFFFAOYSA-N n-[[5-[3-(cyclohexylmethylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CC(CC2)NCC2CCCCC2)=C1 SERLGPIXTTUKMR-UHFFFAOYSA-N 0.000 description 1
• XRTQWHAWFTWZQT-UHFFFAOYSA-N n-[[5-[3-(dodecylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1C(NCCCCCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 XRTQWHAWFTWZQT-UHFFFAOYSA-N 0.000 description 1
• GKEBJYVWVMHPNH-UHFFFAOYSA-N n-[[5-[3-(heptylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1C(NCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 GKEBJYVWVMHPNH-UHFFFAOYSA-N 0.000 description 1
• NPRYDXVECUDIFH-UHFFFAOYSA-N n-[[5-[3-(hexylamino)pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1C(NCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 NPRYDXVECUDIFH-UHFFFAOYSA-N 0.000 description 1
• BZXQOWIECILVKG-JSTNZPBCSA-N n-[[5-[3-[[(1s,3r,4r)-3-bicyclo[2.2.1]heptanyl]amino]pyrrolidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound N([C@H]1[C@]2([H])CC[C@@](C2)(C1)[H])C(C1)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 BZXQOWIECILVKG-JSTNZPBCSA-N 0.000 description 1
• XSGBYNKTCCNLKS-UHFFFAOYSA-N n-[[5-[4-(1-adamantylmethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)NCC23CC4CC(CC(C4)C2)C3)=C1 XSGBYNKTCCNLKS-UHFFFAOYSA-N 0.000 description 1
• RKZRBDPUXPRQPW-UHFFFAOYSA-N n-[[5-[4-(1-adamantylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC23CC4CC(CC(C4)C2)C3)=C1 RKZRBDPUXPRQPW-UHFFFAOYSA-N 0.000 description 1
• ZYGCODOMBDMDLS-UHFFFAOYSA-N n-[[5-[4-(1-adamantylmethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(S(=O)(=O)N2CCC(CC2)NCC23CC4CC(CC(C4)C2)C3)S1 ZYGCODOMBDMDLS-UHFFFAOYSA-N 0.000 description 1
• REAKEZFLPJUGMX-UHFFFAOYSA-N n-[[5-[4-(2,3-dihydroxypropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC(O)CO)=C1 REAKEZFLPJUGMX-UHFFFAOYSA-N 0.000 description 1
• ZBKMLQJTMYJAES-UHFFFAOYSA-N n-[[5-[4-(2-cyclohexylethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)NCCC2CCCCC2)=C1 ZBKMLQJTMYJAES-UHFFFAOYSA-N 0.000 description 1
• BWZVXGXPQNCMNU-UHFFFAOYSA-N n-[[5-[4-(2-ethylhexylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCC(CC)CCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 BWZVXGXPQNCMNU-UHFFFAOYSA-N 0.000 description 1
• JYLIJHMCGACXOT-UHFFFAOYSA-N n-[[5-[4-(2-ethylhexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCC(CC)CCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 JYLIJHMCGACXOT-UHFFFAOYSA-N 0.000 description 1
• XJUUHVHRPWRCQU-UHFFFAOYSA-N n-[[5-[4-(2-hydroxyethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCO)=C1 XJUUHVHRPWRCQU-UHFFFAOYSA-N 0.000 description 1
• KNKWAANXGSZURL-UHFFFAOYSA-N n-[[5-[4-(3-imidazol-1-ylpropylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)NCCCN2C=NC=C2)=C1 KNKWAANXGSZURL-UHFFFAOYSA-N 0.000 description 1
• SQXCTJBQLYJXPH-UHFFFAOYSA-N n-[[5-[4-(3-imidazol-1-ylpropylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCCCN2C=NC=C2)=C1 SQXCTJBQLYJXPH-UHFFFAOYSA-N 0.000 description 1
• QDTNGIOBKJDZAT-UHFFFAOYSA-N n-[[5-[4-(butylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 QDTNGIOBKJDZAT-UHFFFAOYSA-N 0.000 description 1
• PRRXFIRBCBVHNY-UHFFFAOYSA-N n-[[5-[4-(butylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1CC(NCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 PRRXFIRBCBVHNY-UHFFFAOYSA-N 0.000 description 1
• SWJFETHHKUJUKC-UHFFFAOYSA-N n-[[5-[4-(butylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 SWJFETHHKUJUKC-UHFFFAOYSA-N 0.000 description 1
• YFMLZVPBTJYRAE-UHFFFAOYSA-N n-[[5-[4-(butylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1CC(NCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 YFMLZVPBTJYRAE-UHFFFAOYSA-N 0.000 description 1
• VMUITQMEIFXYSI-UHFFFAOYSA-N n-[[5-[4-(cyclohexylmethylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CCC2)NCC2CCCCC2)=C1 VMUITQMEIFXYSI-UHFFFAOYSA-N 0.000 description 1
• ASNFRUWIAXUQCE-UHFFFAOYSA-N n-[[5-[4-(decylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 ASNFRUWIAXUQCE-UHFFFAOYSA-N 0.000 description 1
• AHHWHQBGQQEZBX-UHFFFAOYSA-N n-[[5-[4-(dodecylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCCCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 AHHWHQBGQQEZBX-UHFFFAOYSA-N 0.000 description 1
• QHNZKMJXKUOTKJ-UHFFFAOYSA-N n-[[5-[4-(dodecylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 QHNZKMJXKUOTKJ-UHFFFAOYSA-N 0.000 description 1
• OPBMPAWOBNKSQI-UHFFFAOYSA-N n-[[5-[4-(ethylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 OPBMPAWOBNKSQI-UHFFFAOYSA-N 0.000 description 1
• ZCLGLTGKEPVHGJ-UHFFFAOYSA-N n-[[5-[4-(heptylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 ZCLGLTGKEPVHGJ-UHFFFAOYSA-N 0.000 description 1
• MSEVCYYRWIFFMQ-UHFFFAOYSA-N n-[[5-[4-(hexylamino)azepan-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCC)CCCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 MSEVCYYRWIFFMQ-UHFFFAOYSA-N 0.000 description 1
• PMXPOABEASCNDB-UHFFFAOYSA-N n-[[5-[4-(hexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-2-hydroxybenzamide Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC=C1O PMXPOABEASCNDB-UHFFFAOYSA-N 0.000 description 1
• VTKJUWWSYDUOTP-UHFFFAOYSA-N n-[[5-[4-(hexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-2-oxo-1h-pyridine-3-carboxamide Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CNC1=O VTKJUWWSYDUOTP-UHFFFAOYSA-N 0.000 description 1
• RVLXBEJFSCUIDV-UHFFFAOYSA-N n-[[5-[4-(hexylamino)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(NCCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 RVLXBEJFSCUIDV-UHFFFAOYSA-N 0.000 description 1
• MGOOYKMCBKKAET-UHFFFAOYSA-N n-[[5-[4-(hydroxymethyl)piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CO)CC2)=C1 MGOOYKMCBKKAET-UHFFFAOYSA-N 0.000 description 1
• NMQOFBZKRUPPRK-UHFFFAOYSA-N n-[[5-[4-[(3-ethoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound CCOC1=CC=CC(CNC2CCN(CC2)S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)=C1 NMQOFBZKRUPPRK-UHFFFAOYSA-N 0.000 description 1
• URIPWGBOHDBVGI-UHFFFAOYSA-N n-[[5-[4-[(4-butoxyphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1=CC(OCCCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 URIPWGBOHDBVGI-UHFFFAOYSA-N 0.000 description 1
• XRXPSQBFKULZLM-UHFFFAOYSA-N n-[[5-[4-[(4-butylanilino)methyl]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1=CC(CCCC)=CC=C1NCC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 XRXPSQBFKULZLM-UHFFFAOYSA-N 0.000 description 1
• GDFFDPMYMQCXSX-UHFFFAOYSA-N n-[[5-[4-[(4-butylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1=CC(CCCC)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CC1 GDFFDPMYMQCXSX-UHFFFAOYSA-N 0.000 description 1
• FOSRLIPIVDTNKW-UHFFFAOYSA-N n-[[5-[4-[(4-chlorophenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(Cl)=CC=2)=C1 FOSRLIPIVDTNKW-UHFFFAOYSA-N 0.000 description 1
• IZGYKYJINBEEAT-UHFFFAOYSA-N n-[[5-[4-[(4-iodophenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(I)=CC=2)=C1 IZGYKYJINBEEAT-UHFFFAOYSA-N 0.000 description 1
• UEHNWZFKDOMFGI-UHFFFAOYSA-N n-[[5-[4-[(4-tert-butylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=CC(=CC=2)C(C)(C)C)=C1 UEHNWZFKDOMFGI-UHFFFAOYSA-N 0.000 description 1
• KYBJGRXKYJXTAN-UHFFFAOYSA-N n-[[5-[4-[(4-tert-butylphenyl)methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1CNC1CCN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CC1 KYBJGRXKYJXTAN-UHFFFAOYSA-N 0.000 description 1
• XVDOZYUIWBXTIN-UHFFFAOYSA-N n-[[5-[4-[2-(butylamino)ethyl]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CC(CCNCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=CC(OC)=C1 XVDOZYUIWBXTIN-UHFFFAOYSA-N 0.000 description 1
• IMJDOYRGXAPQCN-UHFFFAOYSA-N n-[[5-[4-[[3,5-bis(trifluoromethyl)phenyl]methylamino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NCC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C1 IMJDOYRGXAPQCN-UHFFFAOYSA-N 0.000 description 1
• QEHDHRBPLGLGSO-UHFFFAOYSA-N n-[[5-[4-[benzyl(hexyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=CC(Cl)=CC=3)=CC=2)CCC1N(CCCCCC)CC1=CC=CC=C1 QEHDHRBPLGLGSO-UHFFFAOYSA-N 0.000 description 1
• JGKVXEHUGBMXGH-UHFFFAOYSA-N n-[[5-[4-[butyl(hexyl)amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide Chemical compound C1CC(N(CCCC)CCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 JGKVXEHUGBMXGH-UHFFFAOYSA-N 0.000 description 1
• YZYLARBFCGWMJP-UHFFFAOYSA-N n-[[5-[4-[ethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]piperidin-1-yl]sulfonylthiophen-2-yl]methyl]-3-methoxybenzamide Chemical compound C1CN(S(=O)(=O)C=2SC(CNC(=O)C=3C=C(OC)C=CC=3)=CC=2)CCC1N(CC)CC1=CC=C(C(F)(F)F)C=C1 YZYLARBFCGWMJP-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• YNILDRGPFGMCDE-UHFFFAOYSA-N n-ethylfuran-2-amine Chemical compound CCNC1=CC=CO1 YNILDRGPFGMCDE-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• OJSDIMLQIDMVNL-UHFFFAOYSA-N n-methylfuran-2-amine Chemical compound CNC1=CC=CO1 OJSDIMLQIDMVNL-UHFFFAOYSA-N 0.000 description 1
• XJINZNWPEQMMBV-UHFFFAOYSA-N n-methylhexan-1-amine Chemical compound CCCCCCNC XJINZNWPEQMMBV-UHFFFAOYSA-N 0.000 description 1
• DYUWTXWIYMHBQS-UHFFFAOYSA-N n-prop-2-enylprop-2-en-1-amine Chemical compound C=CCNCC=C DYUWTXWIYMHBQS-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• BITOAPGZBZODKM-UHFFFAOYSA-N n-propylfuran-2-amine Chemical compound CCCNC1=CC=CO1 BITOAPGZBZODKM-UHFFFAOYSA-N 0.000 description 1
• 210000004897 n-terminal region Anatomy 0.000 description 1
• YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
• 210000003739 neck Anatomy 0.000 description 1
• 230000001338 necrotic effect Effects 0.000 description 1
• 230000008764 nerve damage Effects 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 230000000324 neuroprotective effect Effects 0.000 description 1
• VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 239000007968 orange flavor Substances 0.000 description 1
• 210000003463 organelle Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 229960005010 orotic acid Drugs 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000036542 oxidative stress Effects 0.000 description 1
• 230000000242 pagocytic effect Effects 0.000 description 1
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
• 150000002940 palladium Chemical class 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000009054 pathological process Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 description 1
• 229960001412 pentobarbital Drugs 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 230000008782 phagocytosis Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 125000005561 phenanthryl group Chemical group 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
• 230000000865 phosphorylative effect Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 239000003880 polar aprotic solvent Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 239000010318 polygalacturonic acid Substances 0.000 description 1
• 229920002643 polyglutamic acid Polymers 0.000 description 1
• 229920005990 polystyrene resin Polymers 0.000 description 1
• 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
• 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
• 230000001242 postsynaptic effect Effects 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• OCAAZRFBJBEVPS-UHFFFAOYSA-N prop-2-enyl carbamate Chemical group NC(=O)OCC=C OCAAZRFBJBEVPS-UHFFFAOYSA-N 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 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
• BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
• LPPOVVJDAVMOET-UHFFFAOYSA-N pyrrolidine-1-sulfonamide Chemical class NS(=O)(=O)N1CCCC1 LPPOVVJDAVMOET-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 239000003642 reactive oxygen metabolite Substances 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000011663 regulation of signaling Effects 0.000 description 1
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
• 230000008672 reprogramming Effects 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 230000037390 scarring Effects 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000002356 single layer Substances 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 210000000225 synapse Anatomy 0.000 description 1
• 230000000946 synaptic effect Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000003760 tallow Substances 0.000 description 1
• 229920002258 tannic acid Polymers 0.000 description 1
• 235000015523 tannic acid Nutrition 0.000 description 1
• 229940033123 tannic acid Drugs 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• SOGMBUSBLTXMKX-UHFFFAOYSA-N tert-butyl 2-[[1-[5-[[(4-chlorobenzoyl)amino]methyl]thiophen-2-yl]sulfonylpiperidin-4-yl]-hexylamino]acetate Chemical compound C1CC(N(CC(=O)OC(C)(C)C)CCCCCC)CCN1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1 SOGMBUSBLTXMKX-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
• SEYDWUDASGFNOX-UHFFFAOYSA-N tert-butyl n-[1-[5-[[(3-methoxybenzoyl)amino]methyl]thiophen-2-yl]sulfonylpiperidin-4-yl]carbamate Chemical compound COC1=CC=CC(C(=O)NCC=2SC(=CC=2)S(=O)(=O)N2CCC(CC2)NC(=O)OC(C)(C)C)=C1 SEYDWUDASGFNOX-UHFFFAOYSA-N 0.000 description 1
• CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000001302 tertiary amino group Chemical group 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 238000010257 thawing Methods 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 150000003555 thioacetals Chemical class 0.000 description 1
• 125000004001 thioalkyl group Chemical group 0.000 description 1
• YNVOMSDITJMNET-UHFFFAOYSA-M thiophene-3-carboxylate Chemical compound [O-]C(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-M 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
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 108091006106 transcriptional activators Proteins 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 230000006433 tumor necrosis factor production Effects 0.000 description 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
• 230000029069 type 2 immune response Effects 0.000 description 1
• 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 210000005167 vascular cell Anatomy 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 229940045860 white wax Drugs 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1