ZA200301746B - Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein junkinases. - Google Patents
Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein junkinases. Download PDFInfo
- Publication number
- ZA200301746B ZA200301746B ZA200301746A ZA200301746A ZA200301746B ZA 200301746 B ZA200301746 B ZA 200301746B ZA 200301746 A ZA200301746 A ZA 200301746A ZA 200301746 A ZA200301746 A ZA 200301746A ZA 200301746 B ZA200301746 B ZA 200301746B
- Authority
- ZA
- South Africa
- Prior art keywords
- sulfonyl
- thien
- amino
- methyl
- benzamide
- Prior art date
Links
- 229940124530 sulfonamide Drugs 0.000 title claims description 17
- 150000003456 sulfonamides Chemical class 0.000 title claims description 15
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 title description 8
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 title description 8
- 239000003112 inhibitor Substances 0.000 title description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 214
- -1 pyrrolo Chemical group 0.000 claims description 68
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 63
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 55
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 claims description 39
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 31
- 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 description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 235000013350 formula milk Nutrition 0.000 claims description 20
- 230000037361 pathway Effects 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 claims description 8
- 210000004556 brain Anatomy 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 230000014509 gene expression Effects 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 230000001537 neural effect Effects 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 5
- MNWSGMTUGXNYHJ-UHFFFAOYSA-N 2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(N)=O MNWSGMTUGXNYHJ-UHFFFAOYSA-N 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 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
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 210000002216 heart Anatomy 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 3
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 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 3
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 3
- 201000006370 kidney failure Diseases 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 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 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
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
- 208000006673 asthma Diseases 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
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 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 claims description 2
- 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 claims description 2
- 201000006417 multiple sclerosis Diseases 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
- 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 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 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 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 17
- 229960003966 nicotinamide Drugs 0.000 claims 4
- 239000011570 nicotinamide Substances 0.000 claims 4
- VRJHQPZVIGNGMX-UHFFFAOYSA-N piperidine-4-one Natural products O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 claims 4
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims 3
- 238000002360 preparation method Methods 0.000 claims 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- 102000019145 JUN kinase activity proteins Human genes 0.000 claims 2
- 206010063837 Reperfusion injury Diseases 0.000 claims 2
- 230000002159 abnormal effect Effects 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 235000005152 nicotinamide Nutrition 0.000 claims 2
- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical compound NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 claims 2
- QGKLPGKXAVVPOJ-UHFFFAOYSA-N pyrrolidin-3-one Chemical compound O=C1CCNC1 QGKLPGKXAVVPOJ-UHFFFAOYSA-N 0.000 claims 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 2
- AKXPPROXUJRUJX-UVLQBBPGSA-N (2S)-1-[5-[[(4-chlorobenzoyl)amino]methyl]thiophen-2-yl]sulfonyl-4-(hexylamino)pyrrolidine-2-carboxylic acid ethyl 2-[4-(hexylamino)piperidin-1-yl]sulfonyl-5-[[(3-methoxybenzoyl)amino]methyl]thiophene-3-carboxylate Chemical compound C1C(NCCCCCC)C[C@@H](C(O)=O)N1S(=O)(=O)C(S1)=CC=C1CNC(=O)C1=CC=C(Cl)C=C1.C1CC(NCCCCCC)CCN1S(=O)(=O)C1=C(C(=O)OCC)C=C(CNC(=O)C=2C=C(OC)C=CC=2)S1 AKXPPROXUJRUJX-UVLQBBPGSA-N 0.000 claims 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 claims 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 claims 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 claims 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 claims 1
- 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 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 claims 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 claims 1
- 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 1
- 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 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
- 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 1
- 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 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 claims 1
- 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 1
- 125000003352 4-tert-butyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
- LMLPAAYHTWEBQU-UHFFFAOYSA-N COC=1C=C(C(=O)NCC=2SC(=CC2)S(=O)(=O)N2CC(CC2)NCCCCCCCC)C=CC1.C(CCCCCC)NC1CN(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)N2CC(CC2)NCCCCCCCC)C=CC1.C(CCCCCC)NC1CN(CC1)S(=O)(=O)C1=CC=C(S1)CNC(C1=CC(=CC=C1)OC)=O LMLPAAYHTWEBQU-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
- 206010019196 Head injury Diseases 0.000 claims 1
- 206010061216 Infarction Diseases 0.000 claims 1
- 206010040070 Septic Shock Diseases 0.000 claims 1
- 206010052779 Transplant rejections Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 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 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 230000002440 hepatic effect Effects 0.000 claims 1
- 125000001841 imino group Chemical group [H]N=* 0.000 claims 1
- 230000007574 infarction Effects 0.000 claims 1
- 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 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 claims 1
- 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 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 claims 1
- 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 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 claims 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 claims 1
- 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 1
- 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 1
- 230000002611 ovarian Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 238000006268 reductive amination reaction Methods 0.000 claims 1
- 230000002207 retinal effect Effects 0.000 claims 1
- 229960000581 salicylamide Drugs 0.000 claims 1
- 230000036303 septic shock Effects 0.000 claims 1
- 208000020431 spinal cord injury Diseases 0.000 claims 1
- 230000002381 testicular Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 18
- 230000004913 activation Effects 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 14
- 102000043136 MAP kinase family Human genes 0.000 description 12
- 108091054455 MAP kinase family Proteins 0.000 description 12
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 108010068304 MAP Kinase Kinase 4 Proteins 0.000 description 8
- 102100023132 Transcription factor Jun Human genes 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 230000019491 signal transduction Effects 0.000 description 8
- 230000006907 apoptotic process Effects 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 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
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 4
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- 239000000758 substrate Substances 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
- 101710105206 C-Jun-amino-terminal kinase-interacting protein 1 Proteins 0.000 description 3
- 102100022291 C-Jun-amino-terminal kinase-interacting protein 1 Human genes 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes 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
- 102000002569 MAP Kinase Kinase 4 Human genes 0.000 description 3
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 3
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 3
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 3
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 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
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000001640 apoptogenic effect Effects 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 230000009223 neuronal apoptosis Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108060006633 protein kinase Proteins 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000002222 superior cervical ganglion Anatomy 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 102100025064 Cellular tumor antigen p53 Human genes 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
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 2
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 2
- 101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 239000012825 JNK inhibitor Substances 0.000 description 2
- 101710166851 JNK-interacting protein 1 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-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
- 102000009270 Tumour necrosis factor alpha Human genes 0.000 description 2
- 108050000101 Tumour necrosis factor alpha Proteins 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 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
- 239000005557 antagonist Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 238000003782 apoptosis assay Methods 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
- 230000002950 deficient Effects 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000003492 excitotoxic effect Effects 0.000 description 2
- 231100000063 excitotoxicity Toxicity 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 210000004185 liver Anatomy 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
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 125000006501 nitrophenyl group Chemical group 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 229920001184 polypeptide Polymers 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
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 230000009466 transformation 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
- 238000011144 upstream manufacturing Methods 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
- 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
- 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
- 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
- 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
- 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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
- 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
- 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 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
- 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 description 1
- 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 description 1
- 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 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
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 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
- 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
- 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
- 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
- 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
- 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
- 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 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010051728 Bone erosion Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 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
- 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
- 206010007559 Cardiac failure congestive 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000511343 Chondrostoma nasus Species 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
- 206010010144 Completed suicide Diseases 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
- 102000010170 Death domains Human genes 0.000 description 1
- 108050001718 Death domains Proteins 0.000 description 1
- 102100023332 Dual specificity mitogen-activated protein kinase kinase 7 Human genes 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 101000624594 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 7 Proteins 0.000 description 1
- 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor 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
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 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
- 108010002350 Interleukin-2 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
- 101150026829 JUNB gene Proteins 0.000 description 1
- 108010075654 MAP Kinase Kinase Kinase 1 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 102100033115 Mitogen-activated protein kinase kinase kinase 1 Human genes 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
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000037273 Pathologic Processes Diseases 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
- 108010018070 Proto-Oncogene Proteins c-ets Proteins 0.000 description 1
- 102000004053 Proto-Oncogene Proteins c-ets Human genes 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- 241000283984 Rodentia 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
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108700012920 TNF Proteins 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
- 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
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 241000112708 Vates Species 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000005213 alkyl heteroaryl group Chemical group 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 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
- 230000001580 bacterial effect Effects 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
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 208000002352 blister Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect 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
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 210000003483 chromatin Anatomy 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
- 229940001468 citrate Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003413 degradative effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction 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
- 210000001320 hippocampus Anatomy 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 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
- 230000001976 improved effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 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
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 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
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000004660 morphological change Effects 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
- 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
- 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
- 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
- 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
- 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 description 1
- 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 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
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 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
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000008764 nerve damage 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
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000000242 pagocytic effect Effects 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
- 230000035515 penetration Effects 0.000 description 1
- 230000008782 phagocytosis Effects 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
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 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
- 125000000168 pyrrolyl group Chemical group 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
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000036573 scar formation Effects 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
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000011664 signaling Effects 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
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 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
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 150000003555 thioacetals Chemical class 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
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00810887A EP1193268A1 (en) | 2000-09-27 | 2000-09-27 | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200301746B true ZA200301746B (en) | 2004-03-03 |
Family
ID=8174937
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200301746A ZA200301746B (en) | 2000-09-27 | 2001-09-27 | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein junkinases. |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US7544700B2 (no) |
| EP (2) | EP1193268A1 (no) |
| JP (1) | JP4927304B2 (no) |
| KR (1) | KR20030057532A (no) |
| CN (1) | CN1288150C (no) |
| AR (1) | AR033999A1 (no) |
| AU (2) | AU8799101A (no) |
| BG (1) | BG107633A (no) |
| BR (1) | BR0114223A (no) |
| CA (1) | CA2421209A1 (no) |
| CZ (1) | CZ2003884A3 (no) |
| EA (1) | EA005819B1 (no) |
| EE (1) | EE200300119A (no) |
| ES (1) | ES2438185T3 (no) |
| HK (1) | HK1072768A1 (no) |
| HR (1) | HRP20030214A2 (no) |
| HU (1) | HUP0302980A3 (no) |
| IL (1) | IL154965A0 (no) |
| MX (1) | MXPA03002568A (no) |
| NO (1) | NO20031375D0 (no) |
| NZ (1) | NZ524542A (no) |
| PL (1) | PL361687A1 (no) |
| SK (1) | SK3662003A3 (no) |
| UA (1) | UA75891C2 (no) |
| WO (1) | WO2002026733A2 (no) |
| YU (1) | YU21803A (no) |
| ZA (1) | ZA200301746B (no) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1193256A1 (en) * | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active benzsulfonamide derivatives as inhibitors of JNK proteins |
| EP1193267A1 (en) * | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein JunKinases |
| EP1193268A1 (en) | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases |
| ATE419247T1 (de) * | 2001-07-23 | 2009-01-15 | Serono Lab | Arylsulfonamidderivate als hemmer c-jun- terminaler kinasen (jnk) |
| EP1663193B1 (en) | 2003-09-12 | 2012-04-04 | Merck Serono SA | Sulfonamide derivatives for the treatment of diabetes |
| MXPA06007172A (es) * | 2003-12-23 | 2006-08-23 | Lundbeck & Co As H | Derivados de 2-(1h-indolilsulfanil)-bencilamina como ssri. |
| AR052308A1 (es) * | 2004-07-16 | 2007-03-14 | Lundbeck & Co As H | Derivados de 2-(1h-indolilsulfanil)-arilamina y una composicion farmaceutica que contiene al compuesto |
| US7629473B2 (en) * | 2005-06-17 | 2009-12-08 | H. Lundbeck A/S | 2-(1H-indolylsulfanyl)-aryl amine derivatives |
| AR054393A1 (es) * | 2005-06-17 | 2007-06-20 | Lundbeck & Co As H | Derivados de benzo(b)furano y benzo(b)tiofeno, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por la inhibicion de la reabsorcion de neurotransmisores de amina biogenicos. |
| BRPI0613042A2 (pt) | 2005-07-15 | 2010-12-14 | Serono Lab | inibidores de jnk para o tratamento de endometriose |
| KR20080044836A (ko) | 2005-07-15 | 2008-05-21 | 라보라뚜와르 세로노 에스. 에이. | 자궁내막증 치료용 ｊｎｋ 억제제 |
| AU2011265521B9 (en) * | 2005-07-15 | 2014-05-22 | Merck Serono Sa | JNK inhibitors for the treatment of endometreosis |
| EP2026802A2 (en) * | 2006-06-02 | 2009-02-25 | Laboratoires Serono SA | Jnk inhibitors for treatment of skin diseases |
| WO2010043721A1 (en) | 2008-10-17 | 2010-04-22 | Oryzon Genomics, S.A. | Oxidase inhibitors and their use |
| EP2389362B1 (en) | 2009-01-21 | 2019-12-11 | Oryzon Genomics, S.A. | Phenylcyclopropylamine derivatives and their medical use |
| KR101736218B1 (ko) | 2009-09-25 | 2017-05-16 | 오리존 지노믹스 에스.에이. | 라이신 특이적 디메틸라아제-1 억제제 및 이의 용도 |
| EP2486002B1 (en) | 2009-10-09 | 2019-03-27 | Oryzon Genomics, S.A. | Substituted heteroaryl- and aryl- cyclopropylamine acetamides and their use |
| WO2011106105A2 (en) | 2010-02-24 | 2011-09-01 | Oryzon Genomics, S.A. | Inhibitors for antiviral use |
| WO2011106573A2 (en) | 2010-02-24 | 2011-09-01 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with hepadnaviridae |
| ES2607081T3 (es) | 2010-04-19 | 2017-03-29 | Oryzon Genomics, S.A. | Inhibidores de desmetilasa específica de lisina-1 y su uso |
| HUE037937T2 (hu) | 2010-07-29 | 2021-11-29 | Oryzon Genomics Sa | Arilciklopropilamin-alapú LSD1-demetiláz inhibitorok és gyógyászati alkalmazásuk |
| US9006449B2 (en) | 2010-07-29 | 2015-04-14 | Oryzon Genomics, S.A. | Cyclopropylamine derivatives useful as LSD1 inhibitors |
| US9061966B2 (en) | 2010-10-08 | 2015-06-23 | Oryzon Genomics S.A. | Cyclopropylamine inhibitors of oxidases |
| WO2012072713A2 (en) | 2010-11-30 | 2012-06-07 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with flaviviridae |
| WO2012107498A1 (en) | 2011-02-08 | 2012-08-16 | Oryzon Genomics S.A. | Lysine demethylase inhibitors for myeloproliferative disorders |
| US20140296255A1 (en) * | 2011-05-19 | 2014-10-02 | Oryzong Genomics, S.A. | Lysine demethylase inhibitors for thrombosis and cardiovascular diseases |
| EP2741741A2 (en) * | 2011-05-19 | 2014-06-18 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for inflammatory diseases or conditions |
| EP2768805B1 (en) | 2011-10-20 | 2020-03-25 | Oryzon Genomics, S.A. | (hetero)aryl cyclopropylamine compounds as lsd1 inhibitors |
| PE20141692A1 (es) | 2011-10-20 | 2014-11-08 | Oryzon Genomics Sa | Compuestos de (hetero) aril ciclopropilamina como inhibidores de lsd1 |
| KR101699822B1 (ko) | 2011-12-21 | 2017-01-25 | 노비라 테라퓨틱스, 인코포레이티드 | B형 간염의 항바이러스성 제제 |
| AR092270A1 (es) | 2012-08-28 | 2015-04-08 | Janssen R&D Ireland | Sulfamoilarilamidas y su uso como medicamentos para el tratamiento de la hepatitis b |
| PT2961732T (pt) | 2013-02-28 | 2017-06-26 | Janssen Sciences Ireland Uc | Sulfamoil-arilamidas e utilização das mesmas como medicamentos para o tratamento de hepatite b |
| EA027068B1 (ru) | 2013-04-03 | 2017-06-30 | Янссен Сайенсиз Айрлэнд Юси | Производные n-фенилкарбоксамида и их применение в качестве лекарственных препаратов для лечения гепатита b |
| JP6441315B2 (ja) | 2013-05-17 | 2018-12-19 | ヤンセン・サイエンシズ・アイルランド・ユーシー | スルファモイルチオフェンアミド誘導体およびｂ型肝炎を治療するための医薬品としてのその使用 |
| JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
| US10450270B2 (en) | 2013-07-25 | 2019-10-22 | Janssen Sciences Ireland Uc | Glyoxamide substituted pyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| MX368158B (es) | 2013-10-23 | 2019-09-20 | Janssen Sciences Ireland Uc | Derivados de carboxamida y su uso como medicamentos para el tratamiento de la hepatitis b. |
| US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| MX2016009449A (es) | 2014-02-05 | 2016-10-13 | Novira Therapeutics Inc | Terapia de combinacion para el tratamiento de infecciones por virus de la hepatitis b (vhb). |
| EA035848B1 (ru) | 2014-02-06 | 2020-08-20 | Янссен Сайенсиз Айрлэнд Юси | Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b |
| WO2016149581A1 (en) | 2015-03-19 | 2016-09-22 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis b infections |
| US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| AU2016330964B2 (en) | 2015-09-29 | 2021-04-01 | Novira Therapeutics, Inc. | Crystalline forms of a hepatitis B antiviral agent |
| SG11201808949SA (en) | 2016-04-15 | 2018-11-29 | Novira Therapeutics Inc | Combinations and methods comprising a capsid assembly inhibitor |
| CA3090125A1 (en) | 2018-03-14 | 2019-09-19 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator dosing regimen |
| US11096931B2 (en) | 2019-02-22 | 2021-08-24 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of HBV infection or HBV-induced diseases |
| EP3966205A1 (en) | 2019-05-06 | 2022-03-16 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of hbv infection or hbv-induced diseases |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2553414B1 (fr) * | 1983-10-18 | 1986-08-14 | Choay Sa | Nouveaux benzenesulfonamides n-cyclises, leur procede de preparation et leur utilisation comme substance active de compositions pharmaceutiques |
| US5238950A (en) * | 1991-12-17 | 1993-08-24 | Schering Corporation | Inhibitors of platelet-derived growth factor |
| US5744320A (en) | 1995-06-07 | 1998-04-28 | Promega Corporation | Quenching reagents and assays for enzyme-mediated luminescence |
| CN1159292C (zh) * | 1996-05-31 | 2004-07-28 | 法玛西雅厄普约翰美国公司 | 用作选择性多巴胺d3配体的芳基取代的环胺类化合物 |
| US6043083A (en) | 1997-04-28 | 2000-03-28 | Davis; Roger J. | Inhibitors of the JNK signal transduction pathway and methods of use |
| CA2291778A1 (en) * | 1997-05-29 | 1998-12-03 | Merck & Co., Inc. | Heterocyclic amide compounds as cell adhesion inhibitors |
| DE19743435A1 (de) * | 1997-10-01 | 1999-04-08 | Merck Patent Gmbh | Benzamidinderivate |
| AR019322A1 (es) * | 1998-06-18 | 2002-02-13 | Smithkline Beecham Corp | Derivados de sulfonilo sustituido por heterociclo-etanodionanilina sustituida por heterociclo, composicion farmaceutica que los contiene y su uso para lamanufactura de un medicamento |
| CN1332943C (zh) * | 1998-07-08 | 2007-08-22 | 萨诺费－阿文蒂斯德国有限公司 | 硫取代的磺酰基氨基羧酸n－芳基酰胺,其制备方法、用途以及含有该化合物的药物制剂 |
| EP1088821A1 (en) * | 1999-09-28 | 2001-04-04 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives |
| EP1193268A1 (en) | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases |
| EP1193267A1 (en) * | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein JunKinases |
| EP1193256A1 (en) * | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active benzsulfonamide derivatives as inhibitors of JNK proteins |
-
2000
- 2000-09-27 EP EP00810887A patent/EP1193268A1/en not_active Withdrawn
-
2001
- 2001-09-27 ZA ZA200301746A patent/ZA200301746B/en unknown
- 2001-09-27 EE EEP200300119A patent/EE200300119A/xx unknown
- 2001-09-27 IL IL15496501A patent/IL154965A0/xx unknown
- 2001-09-27 SK SK366-2003A patent/SK3662003A3/sk not_active Application Discontinuation
- 2001-09-27 PL PL36168701A patent/PL361687A1/xx not_active Application Discontinuation
- 2001-09-27 BR BR0114223-2A patent/BR0114223A/pt not_active IP Right Cessation
- 2001-09-27 AR ARP010104565A patent/AR033999A1/es unknown
- 2001-09-27 AU AU8799101A patent/AU8799101A/xx active Pending
- 2001-09-27 JP JP2002531117A patent/JP4927304B2/ja not_active Expired - Fee Related
- 2001-09-27 KR KR10-2003-7004265A patent/KR20030057532A/ko not_active Application Discontinuation
- 2001-09-27 AU AU2001287991A patent/AU2001287991B2/en not_active Ceased
- 2001-09-27 EP EP01967622.0A patent/EP1322642B1/en not_active Expired - Lifetime
- 2001-09-27 CZ CZ2003884A patent/CZ2003884A3/cs unknown
- 2001-09-27 US US10/381,665 patent/US7544700B2/en not_active Expired - Fee Related
- 2001-09-27 CA CA002421209A patent/CA2421209A1/en not_active Abandoned
- 2001-09-27 CN CNB01819141XA patent/CN1288150C/zh not_active Expired - Fee Related
- 2001-09-27 ES ES01967622.0T patent/ES2438185T3/es not_active Expired - Lifetime
- 2001-09-27 EA EA200300412A patent/EA005819B1/ru not_active IP Right Cessation
- 2001-09-27 UA UA2003032606A patent/UA75891C2/uk unknown
- 2001-09-27 YU YU21803A patent/YU21803A/sh unknown
- 2001-09-27 NZ NZ524542A patent/NZ524542A/en unknown
- 2001-09-27 MX MXPA03002568A patent/MXPA03002568A/es not_active Application Discontinuation
- 2001-09-27 HU HU0302980A patent/HUP0302980A3/hu unknown
- 2001-09-27 WO PCT/IB2001/001772 patent/WO2002026733A2/en active IP Right Grant
-
2003
- 2003-03-13 BG BG107633A patent/BG107633A/bg unknown
- 2003-03-20 HR HR20030214A patent/HRP20030214A2/hr not_active Application Discontinuation
- 2003-03-26 NO NO20031375A patent/NO20031375D0/no not_active Application Discontinuation
-
2005
- 2005-04-29 HK HK05103676A patent/HK1072768A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200301746B (en) | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein junkinases. | |
| US8008341B2 (en) | Pharmaceutically active benzsulfonamide derivatives as inhibitors of protein junkinases | |
| AU2001287991A1 (en) | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein junkinases | |
| NO324792B1 (no) | Farmasoytisk aktive sulfonamidderivater | |
| AU2001287992A1 (en) | Pharmaceutically active benzsulfonamide derivatives as inhibitors of protein junkinases | |
| JP2012111777A (ja) | 薬剤活性のあるスルホニルアミノ酸誘導体 | |
| JP4927306B2 (ja) | タンパク質Ｊｕｎ−キナーゼのインヒビターとしての医薬的活性親水性スルホンアミド誘導体 | |
| AU2001287990A1 (en) | Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein junkinases | |
| JP4414219B2 (ja) | Ｃ−ｊｕｎ−ｎ−末端キナーゼ（ｊｎｋ）インヒビターとしてのアリールスルホンアミド誘導体 | |
| MXPA06011575A (en) | Composition comprising a jnk inhibitor and cyclosporin |