CA2396824C - Heteroaromatic carboxamide derivatives and their use as inhibitors of the enzyme ikk-2 - Google Patents
Heteroaromatic carboxamide derivatives and their use as inhibitors of the enzyme ikk-2 Download PDFInfo
- Publication number
- CA2396824C CA2396824C CA2396824A CA2396824A CA2396824C CA 2396824 C CA2396824 C CA 2396824C CA 2396824 A CA2396824 A CA 2396824A CA 2396824 A CA2396824 A CA 2396824A CA 2396824 C CA2396824 C CA 2396824C
- Authority
- CA
- Canada
- Prior art keywords
- amino
- thiophenecarboxamide
- aminocarbonyl
- phenyl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 125000001072 heteroaryl group Chemical group 0.000 title claims description 13
- 102000004190 Enzymes Human genes 0.000 title description 5
- 108090000790 Enzymes Proteins 0.000 title description 5
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 title description 3
- 239000003112 inhibitor Substances 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 101
- -1 heteroaromatic carboxamides Chemical class 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 230000008569 process Effects 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 88
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 67
- 150000003839 salts Chemical class 0.000 claims description 44
- 230000003287 optical effect Effects 0.000 claims description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 239000012453 solvate Substances 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 239000011593 sulfur Substances 0.000 claims description 9
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 229930192474 thiophene Natural products 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 239000005864 Sulphur Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- QQZVZIZPJRWDJD-UHFFFAOYSA-N 2-(carbamoylamino)-4-methyl-5-phenylthiophene-3-carboxamide Chemical compound S1C(NC(N)=O)=C(C(N)=O)C(C)=C1C1=CC=CC=C1 QQZVZIZPJRWDJD-UHFFFAOYSA-N 0.000 claims description 4
- BXIPBPGAJAHULV-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-hydroxyphenyl)thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=CC(O)=CC=2)=C1 BXIPBPGAJAHULV-UHFFFAOYSA-N 0.000 claims description 4
- IZDMGIFTGJJRIC-UHFFFAOYSA-N 3-(carbamoylamino)-5-(2-methoxyphenyl)thiophene-2-carboxamide Chemical compound COC1=CC=CC=C1C1=CC(NC(N)=O)=C(C(N)=O)S1 IZDMGIFTGJJRIC-UHFFFAOYSA-N 0.000 claims description 4
- ZTIWLEXWFMLTQD-UHFFFAOYSA-N 3-(carbamoylamino)-5-[2-[2-(dimethylamino)ethoxy]phenyl]thiophene-2-carboxamide Chemical compound CN(C)CCOC1=CC=CC=C1C1=CC(NC(N)=O)=C(C(N)=O)S1 ZTIWLEXWFMLTQD-UHFFFAOYSA-N 0.000 claims description 4
- CYEQODIYTZSLEN-UHFFFAOYSA-N 3-(carbamoylamino)-5-[4-[2-(dimethylamino)ethoxy]phenyl]thiophene-2-carboxamide Chemical compound C1=CC(OCCN(C)C)=CC=C1C1=CC(NC(N)=O)=C(C(N)=O)S1 CYEQODIYTZSLEN-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- ATBVEMCPWCNKAL-UHFFFAOYSA-N 2-(carbamothioylamino)-5-phenylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=S)N)SC(C=2C=CC=CC=2)=C1 ATBVEMCPWCNKAL-UHFFFAOYSA-N 0.000 claims description 3
- SDLHAVROROHUBG-UHFFFAOYSA-N 2-(carbamoylamino)-4-ethyl-5-phenylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2C=CC=CC=2)=C1CC SDLHAVROROHUBG-UHFFFAOYSA-N 0.000 claims description 3
- XGWCGJSJBKWZMI-UHFFFAOYSA-N 2-(carbamoylamino)-4-methyl-5-(3,4,5-trimethoxyphenyl)thiophene-3-carboxamide Chemical compound COC1=C(OC)C(OC)=CC(C2=C(C(C(N)=O)=C(NC(N)=O)S2)C)=C1 XGWCGJSJBKWZMI-UHFFFAOYSA-N 0.000 claims description 3
- NZIYDXMBIZCEKY-UHFFFAOYSA-N 2-(carbamoylamino)-4-methyl-5-(4-methylphenyl)thiophene-3-carboxamide Chemical compound S1C(NC(N)=O)=C(C(N)=O)C(C)=C1C1=CC=C(C)C=C1 NZIYDXMBIZCEKY-UHFFFAOYSA-N 0.000 claims description 3
- JPWRQYSXPRDVAA-UHFFFAOYSA-N 2-(carbamoylamino)-4-methyl-5-(4-propan-2-ylphenyl)thiophene-3-carboxamide Chemical compound C1=CC(C(C)C)=CC=C1C1=C(C)C(C(N)=O)=C(NC(N)=O)S1 JPWRQYSXPRDVAA-UHFFFAOYSA-N 0.000 claims description 3
- CXTHSHHAIJQMJR-UHFFFAOYSA-N 2-(carbamoylamino)-4-methyl-5-[4-(2-piperidin-1-ylethoxy)phenyl]thiophene-3-carboxamide Chemical compound S1C(NC(N)=O)=C(C(N)=O)C(C)=C1C(C=C1)=CC=C1OCCN1CCCCC1 CXTHSHHAIJQMJR-UHFFFAOYSA-N 0.000 claims description 3
- SMXLQZQJGMJJAH-UHFFFAOYSA-N 2-(carbamoylamino)-4-methyl-5-pyrazin-2-ylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2N=CC=NC=2)=C1C SMXLQZQJGMJJAH-UHFFFAOYSA-N 0.000 claims description 3
- YTSMDSUOXYWBIL-UHFFFAOYSA-N 2-(carbamoylamino)-5-(2,3-dimethoxyphenyl)-4-methylthiophene-3-carboxamide Chemical compound COC1=CC=CC(C2=C(C(C(N)=O)=C(NC(N)=O)S2)C)=C1OC YTSMDSUOXYWBIL-UHFFFAOYSA-N 0.000 claims description 3
- CLPFREPZDLOUQD-UHFFFAOYSA-N 2-(carbamoylamino)-5-(3,5-dimethyl-1,2-oxazol-4-yl)thiophene-3-carboxamide Chemical compound CC1=NOC(C)=C1C1=CC(C(N)=O)=C(NC(N)=O)S1 CLPFREPZDLOUQD-UHFFFAOYSA-N 0.000 claims description 3
- KMVRILPXROLFES-UHFFFAOYSA-N 2-(carbamoylamino)-5-(3-chloro-4-methoxyphenyl)-4-methylthiophene-3-carboxamide Chemical compound C1=C(Cl)C(OC)=CC=C1C1=C(C)C(C(N)=O)=C(NC(N)=O)S1 KMVRILPXROLFES-UHFFFAOYSA-N 0.000 claims description 3
- WOCVVZHRWJHXPQ-UHFFFAOYSA-N 2-(carbamoylamino)-5-(3-fluorophenyl)-4-methylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2C=C(F)C=CC=2)=C1C WOCVVZHRWJHXPQ-UHFFFAOYSA-N 0.000 claims description 3
- FVBQZSLVARNBKI-UHFFFAOYSA-N 2-(carbamoylamino)-5-(3-methoxyphenyl)-4-methylthiophene-3-carboxamide Chemical compound COC1=CC=CC(C2=C(C(C(N)=O)=C(NC(N)=O)S2)C)=C1 FVBQZSLVARNBKI-UHFFFAOYSA-N 0.000 claims description 3
- LJDWXGLSTKMDFA-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-chlorophenyl)-4-methylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2C=CC(Cl)=CC=2)=C1C LJDWXGLSTKMDFA-UHFFFAOYSA-N 0.000 claims description 3
- WPYPRHJBDHULLS-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-chlorophenyl)thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=CC(Cl)=CC=2)=C1 WPYPRHJBDHULLS-UHFFFAOYSA-N 0.000 claims description 3
- LNPHMBRNCVPNDD-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-cyanophenyl)-4-methylthiophene-3-carboxamide Chemical compound S1C(NC(N)=O)=C(C(N)=O)C(C)=C1C1=CC=C(C#N)C=C1 LNPHMBRNCVPNDD-UHFFFAOYSA-N 0.000 claims description 3
- CDUVIKAVHUBTFR-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-fluorophenyl)-4-methylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2C=CC(F)=CC=2)=C1C CDUVIKAVHUBTFR-UHFFFAOYSA-N 0.000 claims description 3
- XDWCHVTXXSDZPW-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-hydroxyphenyl)-4-methylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2C=CC(O)=CC=2)=C1C XDWCHVTXXSDZPW-UHFFFAOYSA-N 0.000 claims description 3
- KLTHOXLEZZZIKF-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-methoxy-3-methylphenyl)-4-methylthiophene-3-carboxamide Chemical compound C1=C(C)C(OC)=CC=C1C1=C(C)C(C(N)=O)=C(NC(N)=O)S1 KLTHOXLEZZZIKF-UHFFFAOYSA-N 0.000 claims description 3
- COYICBSHVUAHQG-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-methoxyphenyl)-4-methylthiophene-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C)C(C(N)=O)=C(NC(N)=O)S1 COYICBSHVUAHQG-UHFFFAOYSA-N 0.000 claims description 3
- BDZUXXVCUNXOPR-UHFFFAOYSA-N 2-(carbamoylamino)-5-(furan-2-yl)thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2OC=CC=2)=C1 BDZUXXVCUNXOPR-UHFFFAOYSA-N 0.000 claims description 3
- AXXSGOUYJMRDBJ-UHFFFAOYSA-N 2-(carbamoylamino)-5-(furan-3-yl)thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C2=COC=C2)=C1 AXXSGOUYJMRDBJ-UHFFFAOYSA-N 0.000 claims description 3
- UQXDOVBNWLUIAF-UHFFFAOYSA-N 2-(carbamoylamino)-5-[4-(1,3-thiazol-4-ylmethoxy)phenyl]thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=CC(OCC=3N=CSC=3)=CC=2)=C1 UQXDOVBNWLUIAF-UHFFFAOYSA-N 0.000 claims description 3
- SCBVWSFCSHHZTA-UHFFFAOYSA-N 2-(carbamoylamino)-5-[4-(2-piperidin-1-ylethoxy)phenyl]thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=CC(OCCN3CCCCC3)=CC=2)=C1 SCBVWSFCSHHZTA-UHFFFAOYSA-N 0.000 claims description 3
- POZWZZAJFLHFAG-UHFFFAOYSA-N 2-(carbamoylamino)-5-[4-[2-(diethylamino)ethoxy]phenyl]-4-methylthiophene-3-carboxamide Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C1=C(C)C(C(N)=O)=C(NC(N)=O)S1 POZWZZAJFLHFAG-UHFFFAOYSA-N 0.000 claims description 3
- NYZIZMIEXUUSLK-UHFFFAOYSA-N 2-(carbamoylamino)-5-[4-[2-(diethylamino)ethoxy]phenyl]thiophene-3-carboxamide Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C1=CC(C(N)=O)=C(NC(N)=O)S1 NYZIZMIEXUUSLK-UHFFFAOYSA-N 0.000 claims description 3
- RFSVVCBVIFWEMZ-UHFFFAOYSA-N 2-(carbamoylamino)-5-[4-[2-(dimethylamino)ethoxy]phenyl]thiophene-3-carboxamide Chemical compound C1=CC(OCCN(C)C)=CC=C1C1=CC(C(N)=O)=C(NC(N)=O)S1 RFSVVCBVIFWEMZ-UHFFFAOYSA-N 0.000 claims description 3
- SMJJKGGHJUSUHR-UHFFFAOYSA-N 2-(carbamoylamino)-5-phenyl-4-(trifluoromethyl)thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=CC=CC=2)=C1C(F)(F)F SMJJKGGHJUSUHR-UHFFFAOYSA-N 0.000 claims description 3
- FLGCIFCXVAFWLT-UHFFFAOYSA-N 2-(carbamoylamino)-5-pyridin-3-ylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=NC=CC=2)=C1 FLGCIFCXVAFWLT-UHFFFAOYSA-N 0.000 claims description 3
- GIDGPFNZBRRNRV-UHFFFAOYSA-N 3-(carbamoylamino)-5-(3-hydroxyphenyl)thiophene-2-carboxamide Chemical compound S1C(C(N)=O)=C(NC(=O)N)C=C1C1=CC=CC(O)=C1 GIDGPFNZBRRNRV-UHFFFAOYSA-N 0.000 claims description 3
- TZNIVANCRGBJFY-UHFFFAOYSA-N 3-(carbamoylamino)-5-(3-methoxyphenyl)thiophene-2-carboxamide Chemical compound COC1=CC=CC(C=2SC(=C(NC(N)=O)C=2)C(N)=O)=C1 TZNIVANCRGBJFY-UHFFFAOYSA-N 0.000 claims description 3
- JLVQRNZTRSPEHQ-UHFFFAOYSA-N 3-(carbamoylamino)-5-[2-(2-pyrrolidin-1-ylethoxy)phenyl]thiophene-2-carboxamide Chemical compound S1C(C(N)=O)=C(NC(=O)N)C=C1C1=CC=CC=C1OCCN1CCCC1 JLVQRNZTRSPEHQ-UHFFFAOYSA-N 0.000 claims description 3
- OXOHISRDNOBQSP-UHFFFAOYSA-N 3-(carbamoylamino)-5-[3-(2-piperidin-1-ylethoxy)phenyl]thiophene-2-carboxamide Chemical compound S1C(C(N)=O)=C(NC(=O)N)C=C1C1=CC=CC(OCCN2CCCCC2)=C1 OXOHISRDNOBQSP-UHFFFAOYSA-N 0.000 claims description 3
- SLONXLUFWDCEBJ-UHFFFAOYSA-N 3-(carbamoylamino)-5-[3-(2-pyrrolidin-1-ylethoxy)phenyl]thiophene-2-carboxamide Chemical compound S1C(C(N)=O)=C(NC(=O)N)C=C1C1=CC=CC(OCCN2CCCC2)=C1 SLONXLUFWDCEBJ-UHFFFAOYSA-N 0.000 claims description 3
- UBGJXCDOCIXCJC-UHFFFAOYSA-N 3-(carbamoylamino)-5-[4-(2-methylpropyl)phenyl]thiophene-2-carboxamide Chemical compound C1=CC(CC(C)C)=CC=C1C1=CC(NC(N)=O)=C(C(N)=O)S1 UBGJXCDOCIXCJC-UHFFFAOYSA-N 0.000 claims description 3
- XZJDTLHIAQZDKI-UHFFFAOYSA-N 3-(carbamoylamino)-5-[4-(2-piperidin-1-ylethoxy)phenyl]thiophene-2-carboxamide Chemical compound S1C(C(N)=O)=C(NC(=O)N)C=C1C(C=C1)=CC=C1OCCN1CCCCC1 XZJDTLHIAQZDKI-UHFFFAOYSA-N 0.000 claims description 3
- ZDQLZTAJWGOWEF-UHFFFAOYSA-N 3-(carbamoylamino)-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]thiophene-2-carboxamide Chemical compound S1C(C(N)=O)=C(NC(=O)N)C=C1C(C=C1)=CC=C1OCCN1CCCC1 ZDQLZTAJWGOWEF-UHFFFAOYSA-N 0.000 claims description 3
- AZFVZMKCOBJRAW-UHFFFAOYSA-N 3-(carbamoylamino)-5-thiophen-3-ylthiophene-2-carboxamide Chemical compound S1C(C(N)=O)=C(NC(=O)N)C=C1C1=CSC=C1 AZFVZMKCOBJRAW-UHFFFAOYSA-N 0.000 claims description 3
- OJSUVLRFSLPFGL-UHFFFAOYSA-N 5-(carbamoylamino)-2-(3,5-dichlorophenyl)-1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)OC(C=2C=C(Cl)C=C(Cl)C=2)=N1 OJSUVLRFSLPFGL-UHFFFAOYSA-N 0.000 claims description 3
- WQAOYOSIGJNDHS-UHFFFAOYSA-N 5-(carbamoylamino)-2-[4-(trifluoromethyl)phenyl]-1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 WQAOYOSIGJNDHS-UHFFFAOYSA-N 0.000 claims description 3
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- YCKNYGUFYNQBQL-UHFFFAOYSA-N 2-(carbamoylamino)-4-methyl-5-(3-methyl-1,2-oxazol-5-yl)thiophene-3-carboxamide Chemical compound O1N=C(C)C=C1C1=C(C)C(C(N)=O)=C(NC(N)=O)S1 YCKNYGUFYNQBQL-UHFFFAOYSA-N 0.000 claims description 2
- WKWIWHYBWOYYKN-UHFFFAOYSA-N 2-(carbamoylamino)-4-methyl-5-[3-(trifluoromethyl)phenyl]thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2C=C(C=CC=2)C(F)(F)F)=C1C WKWIWHYBWOYYKN-UHFFFAOYSA-N 0.000 claims description 2
- PHNQCLZNDMMADB-UHFFFAOYSA-N 2-(carbamoylamino)-5-(2,4-difluorophenyl)thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C(=CC(F)=CC=2)F)=C1 PHNQCLZNDMMADB-UHFFFAOYSA-N 0.000 claims description 2
- NHNDJPHJRKXSPD-UHFFFAOYSA-N 2-(carbamoylamino)-5-(2-chlorophenyl)-4-methylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2C(=CC=CC=2)Cl)=C1C NHNDJPHJRKXSPD-UHFFFAOYSA-N 0.000 claims description 2
- FAMJKPLELMLHSY-UHFFFAOYSA-N 2-(carbamoylamino)-5-(3,4-dichlorophenyl)-4-methylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(N)=O)SC(C=2C=C(Cl)C(Cl)=CC=2)=C1C FAMJKPLELMLHSY-UHFFFAOYSA-N 0.000 claims description 2
- FEEIBVYVIHWTBM-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-cyanophenyl)thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=CC(=CC=2)C#N)=C1 FEEIBVYVIHWTBM-UHFFFAOYSA-N 0.000 claims description 2
- LNMXHBQGPRUADI-UHFFFAOYSA-N 2-(carbamoylamino)-5-(4-methylsulfonylphenyl)thiophene-3-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CC(C(N)=O)=C(NC(N)=O)S1 LNMXHBQGPRUADI-UHFFFAOYSA-N 0.000 claims description 2
- NRRMPQZZBHIDOC-UHFFFAOYSA-N 2-(carbamoylamino)-5-[4-(trifluoromethyl)phenyl]thiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=CC(=CC=2)C(F)(F)F)=C1 NRRMPQZZBHIDOC-UHFFFAOYSA-N 0.000 claims description 2
- PSVUSJKZJQMCSP-UHFFFAOYSA-N 2-(carbamoylamino)-5-phenylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=CC=CC=2)=C1 PSVUSJKZJQMCSP-UHFFFAOYSA-N 0.000 claims description 2
- UUGTXTYLCCKUTO-UHFFFAOYSA-N 2-(carbamoylamino)-5-pyridin-2-ylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2N=CC=CC=2)=C1 UUGTXTYLCCKUTO-UHFFFAOYSA-N 0.000 claims description 2
- XEFCHXAXZNYWJN-UHFFFAOYSA-N 2-(carbamoylamino)-5-pyrimidin-5-ylthiophene-3-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N)SC(C=2C=NC=NC=2)=C1 XEFCHXAXZNYWJN-UHFFFAOYSA-N 0.000 claims description 2
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- SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- YIQJFQMRWXPBSJ-UHFFFAOYSA-N methyl 3-amino-5-(2-chlorophenyl)thiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2C(=CC=CC=2)Cl)=C1 YIQJFQMRWXPBSJ-UHFFFAOYSA-N 0.000 description 1
- NRDZDYYBFKCMBW-UHFFFAOYSA-N methyl 3-amino-5-(3-chlorophenyl)thiophene-2-carboxylate phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O.NC1=C(C(=O)OC)SC(C=2C=C(Cl)C=CC=2)=C1 NRDZDYYBFKCMBW-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
- 235000007708 morin Nutrition 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- UPDSKMGGWRHAPJ-UHFFFAOYSA-N n-(5-bromo-3-cyanothiophen-2-yl)acetamide;n-(3-cyanothiophen-2-yl)acetamide Chemical compound CC(=O)NC=1SC=CC=1C#N.CC(=O)NC=1SC(Br)=CC=1C#N UPDSKMGGWRHAPJ-UHFFFAOYSA-N 0.000 description 1
- PJQWWZGIYZGSLH-UHFFFAOYSA-N n-(5-bromo-3-cyanothiophen-2-yl)acetamide;n-[3-cyano-5-(4-cyanophenyl)thiophen-2-yl]acetamide Chemical compound CC(=O)NC=1SC(Br)=CC=1C#N.N#CC1=C(NC(=O)C)SC(C=2C=CC(=CC=2)C#N)=C1 PJQWWZGIYZGSLH-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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- QCCDLTOVEPVEJK-UHFFFAOYSA-N phenylacetone Chemical compound CC(=O)CC1=CC=CC=C1 QCCDLTOVEPVEJK-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-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
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 102000030938 small GTPase Human genes 0.000 description 1
- 108060007624 small GTPase Proteins 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.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 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 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
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- MQAYPFVXSPHGJM-UHFFFAOYSA-M trimethyl(phenyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)C1=CC=CC=C1 MQAYPFVXSPHGJM-UHFFFAOYSA-M 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D333/40—Thiophene-2-carboxylic acid
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0003154.2A GB0003154D0 (en) | 2000-02-12 | 2000-02-12 | Novel compounds |
| GB0003154.2 | 2000-02-12 | ||
| PCT/SE2001/000248 WO2001058890A1 (en) | 2000-02-12 | 2001-02-07 | Heteroaromatic carboxamide derivatives and their use as inhibitors of the enzyme ikk-2 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2396824A1 CA2396824A1 (en) | 2001-08-16 |
| CA2396824C true CA2396824C (en) | 2010-11-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2396824A Expired - Fee Related CA2396824C (en) | 2000-02-12 | 2001-02-07 | Heteroaromatic carboxamide derivatives and their use as inhibitors of the enzyme ikk-2 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US7358376B2 (enExample) |
| EP (1) | EP1261600B1 (enExample) |
| JP (1) | JP4812999B2 (enExample) |
| KR (1) | KR100738165B1 (enExample) |
| CN (1) | CN1243747C (enExample) |
| AT (1) | ATE266019T1 (enExample) |
| AU (1) | AU781047B2 (enExample) |
| BR (1) | BR0108143A (enExample) |
| CA (1) | CA2396824C (enExample) |
| DE (1) | DE60103132T2 (enExample) |
| DK (1) | DK1261600T3 (enExample) |
| ES (1) | ES2218376T3 (enExample) |
| GB (1) | GB0003154D0 (enExample) |
| IL (2) | IL150482A0 (enExample) |
| MX (1) | MXPA02007734A (enExample) |
| NO (1) | NO327741B1 (enExample) |
| NZ (1) | NZ519947A (enExample) |
| PT (1) | PT1261600E (enExample) |
| TR (1) | TR200401962T4 (enExample) |
| WO (1) | WO2001058890A1 (enExample) |
| ZA (1) | ZA200205300B (enExample) |
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| US6869956B2 (en) | 2000-10-03 | 2005-03-22 | Bristol-Myers Squibb Company | Methods of treating inflammatory and immune diseases using inhibitors of IκB kinase (IKK) |
| JP2004523476A (ja) * | 2000-10-12 | 2004-08-05 | スミスクライン・ビーチャム・コーポレイション | ＮＦ−κＢ阻害剤 |
| CA2427284A1 (en) | 2000-10-26 | 2002-05-30 | Tularik Inc. | Antiinflammation agents |
| WO2002060386A2 (en) * | 2001-02-01 | 2002-08-08 | Bristol-Myers Squibb Company | METHODS OF TREATING INFLAMMATORY AND IMMUNE DISEASES USING INHIBITORS OF IλB KINASE (IKK) |
| SI1401825T1 (sl) * | 2001-06-11 | 2010-01-29 | Virochem Pharma Inc | Tiofenski derivati kot protivirusna sredstva za flavirusno infekcijo |
| US8329924B2 (en) * | 2001-06-11 | 2012-12-11 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
| SE0102616D0 (sv) * | 2001-07-25 | 2001-07-25 | Astrazeneca Ab | Novel compounds |
| MXPA04002667A (es) * | 2001-09-19 | 2004-06-18 | Pharmacia Corp | Compuestos de pirazolilo sustituido para el tratamiento de la inflacion. |
| JP2005504806A (ja) * | 2001-09-21 | 2005-02-17 | スミスクライン・ビーチャム・コーポレイション | 化合物 |
| US7307097B2 (en) | 2001-09-27 | 2007-12-11 | Smithkline Beechman Corporation | Chemical compounds |
| DE60229975D1 (de) | 2001-10-04 | 2009-01-02 | Smithkline Beecham Corp | Nf-kb-inhibitoren |
| WO2003028731A1 (en) * | 2001-10-04 | 2003-04-10 | Smithkline Beecham Corporation | Chk1 kinase inhibitors |
| CA2464924A1 (en) * | 2001-10-30 | 2003-05-08 | Pharmacia Corporation | Heteroaromatic carboxamide derivatives for the treatment of inflammation |
| US7176314B2 (en) | 2001-12-05 | 2007-02-13 | Amgen, Inc. | Inflammation modulators |
| US6974870B2 (en) | 2002-06-06 | 2005-12-13 | Boehringer Ingelheim Phamaceuticals, Inc. | Substituted 3-amino-thieno [2,3-b]pyridine-2-carboxylic acid amide compounds and processes for preparing and their uses |
| JP4364120B2 (ja) | 2002-06-06 | 2009-11-11 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 置換３−アミノ−チエノ［２，３−ｂ］ピリジン−２−カルボン酸アミド化合物、その製造方法及び使用 |
| EP1532133A4 (en) * | 2002-06-06 | 2006-11-15 | Smithkline Beecham Corp | NF-: B INHIBITORS |
| US7179836B2 (en) | 2002-09-20 | 2007-02-20 | Smithkline Beecham Corporation | Chemical compounds |
| CA2502429A1 (en) | 2002-10-31 | 2004-05-21 | Amgen Inc. | Antiinflammation agents |
| US7196106B2 (en) | 2002-11-05 | 2007-03-27 | Merck & Co., Inc | Cyanothiophene derivatives, compositions containing such compounds and methods of use |
| AU2003300832A1 (en) * | 2002-12-06 | 2004-06-30 | Smithkline Beecham Corporation | NF-KappaB INHIBITORS |
| DE60332482D1 (de) | 2002-12-10 | 2010-06-17 | Virochem Pharma Inc | Verbindungen und methoden zum behandeln oder vorbeugen von flavivirus infektionen |
| SE0300091D0 (sv) * | 2003-01-15 | 2003-01-15 | Astrazeneca Ab | Novel compounds |
| SE0300092D0 (sv) * | 2003-01-15 | 2003-01-15 | Astrazeneca Ab | Novel compounds |
| EP1660474B1 (en) | 2003-08-15 | 2008-10-29 | AstraZeneca AB | Substituted thiophenes and uses thereof |
| US20050085531A1 (en) * | 2003-10-03 | 2005-04-21 | Hodge Carl N. | Thiophene-based compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| ATE359283T1 (de) * | 2003-10-14 | 2007-05-15 | Pharmacia Corp | Substituierte pyrazinonverbindungen zur behandlung von entzündungen |
| WO2005037797A1 (en) * | 2003-10-21 | 2005-04-28 | Pharmacia Corporation | Substituted pyrazole urea compounds for the treatment of inflammation |
| EP1732920B1 (en) * | 2004-01-05 | 2011-03-09 | AstraZeneca AB | Thiophene derivatives as chk 1 inhibitors |
| CA2562827A1 (en) * | 2004-04-12 | 2005-10-27 | Sankyo Company Limited | Thienopyridine derivatives |
| WO2005105777A1 (en) * | 2004-05-05 | 2005-11-10 | Pharmacia & Upjohn Company Llc | Substituted thiophene amide compounds for the treatment of inflammation |
| PE20060373A1 (es) | 2004-06-24 | 2006-04-29 | Smithkline Beecham Corp | Derivados 3-piperidinil-7-carboxamida-indazol como inhibidores de la actividad cinasa de ikk2 |
| PE20060748A1 (es) | 2004-09-21 | 2006-10-01 | Smithkline Beecham Corp | Derivados de indolcarboxamida como inhibidores de quinasa ikk2 |
| WO2006036031A1 (ja) * | 2004-09-30 | 2006-04-06 | Takeda Pharmaceutical Company Limited | 縮合フラン誘導体およびその用途 |
| JP5000490B2 (ja) | 2005-04-28 | 2012-08-15 | 武田薬品工業株式会社 | チエノピリミドン化合物 |
| US8063071B2 (en) | 2007-10-31 | 2011-11-22 | GlaxoSmithKline, LLC | Chemical compounds |
| MX2007016541A (es) | 2005-06-30 | 2008-03-07 | Smithkline Beecham Corp | Compuestos quimicos. |
| WO2007146602A1 (en) | 2006-06-06 | 2007-12-21 | Boehringer Ingelheim International Gmbh | Substituted 3-amino-thieno[2,3-b] pyridine-2-carboxamide compounds, their preparation and use |
| AU2007321677B2 (en) | 2006-11-15 | 2013-04-11 | Vertex Pharmaceuticals (Canada) Incorporated | Thiophene analogues for the treatment or prevention of flavivirus infections |
| RU2470918C2 (ru) * | 2007-01-15 | 2012-12-27 | Сантен Фармасьютикал Ко., Лтд. | НОВЫЕ ПРОИЗВОДНЫЕ ИНДОЛА, ОБЛАДАЮЩИЕ ИНГИБИРУЮЩЕЙ АКТИВНОСТЬЮ В ОТНОШЕНИИ IκB КИНАЗЫ β |
| PE20081889A1 (es) | 2007-03-23 | 2009-03-05 | Smithkline Beecham Corp | Indol carboxamidas como inhibidores de ikk2 |
| GB0709031D0 (en) | 2007-05-10 | 2007-06-20 | Sareum Ltd | Pharmaceutical compounds |
| CA2721927C (en) | 2008-04-21 | 2014-01-28 | Otonomy, Inc. | Auris formulations for treating otic diseases and conditions |
| US11969501B2 (en) | 2008-04-21 | 2024-04-30 | Dompé Farmaceutici S.P.A. | Auris formulations for treating otic diseases and conditions |
| US8445529B2 (en) * | 2008-07-14 | 2013-05-21 | Santen Pharmaceutical Co., Ltd. | Indole derivative having, carbamoyl group, ureido group and substituted oxy group |
| JP2010077119A (ja) * | 2008-08-25 | 2010-04-08 | Santen Pharmaceut Co Ltd | ウレイド基、アミノカルボニル基及び置換フェニル基を置換基として有するピロール誘導体を有効成分として含有する骨・関節疾患の予防又は治療剤 |
| JP5492496B2 (ja) * | 2008-08-25 | 2014-05-14 | 参天製薬株式会社 | ウレイド基、アミノカルボニル基及び置換基を有してもよい二環式基を置換基として有する新規ピロール誘導体 |
| WO2010056720A1 (en) * | 2008-11-14 | 2010-05-20 | E. I. Du Pont De Nemours And Company | Method for preparing a non-hydratable crystal form |
| EP2406249A1 (en) | 2009-03-10 | 2012-01-18 | Glaxo Group Limited | Indole derivatives as ikk2 inhibitors |
| GB0913345D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | New combination 802 |
| WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
| WO2012046793A1 (ja) * | 2010-10-07 | 2012-04-12 | 参天製薬株式会社 | ウレイド基とアミノカルボニル基を置換基として有するチオフェン誘導体を有効成分として含有する新規ｊａｋ３阻害剤 |
| GB201016912D0 (en) | 2010-10-07 | 2010-11-24 | Astrazeneca Ab | Novel combination |
| GB201021979D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | New compound |
| GB201021992D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | Compound |
| EP2520292A1 (en) | 2011-05-06 | 2012-11-07 | Helmholtz-Zentrum für Infektionsforschung GmbH | Use of spirangiens for the treatment or prevention of IL-8 or IL-6 mediated disorders |
| GB201202027D0 (en) | 2012-02-06 | 2012-03-21 | Sareum Ltd | Pharmaceutical compounds |
| ES2566205T3 (es) | 2012-03-02 | 2016-04-11 | Sareum Limited | Inhibidores de quinasa TYK2 |
| AU2017290256A1 (en) | 2016-06-29 | 2019-01-17 | Otonomy, Inc. | Triglyceride otic formulations and uses thereof |
| GB201617871D0 (en) | 2016-10-21 | 2016-12-07 | Sareum Limited | Pharmaceutical compounds |
| US11000491B2 (en) | 2017-05-05 | 2021-05-11 | Hepanova, Inc. | Amino-aryl-benzamide compounds and methods of use thereof |
| GB201816369D0 (en) | 2018-10-08 | 2018-11-28 | Sareum Ltd | Pharmaceutical compounds |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1468012A (en) | 1973-08-09 | 1977-03-23 | Beecham Group Ltd | 2-amino-3-carboxy-thiophene derivatives |
| DE3529247A1 (de) | 1985-05-17 | 1986-11-20 | Bayer Ag, 5090 Leverkusen | Verwendung von thienylharnstoffen und -isoharnstoffen als leistungsfoerdernde mittel bei tieren, neue thienylharnstoffe und -isoharnstoffe und ihre herstellung |
| US5258357A (en) * | 1989-10-07 | 1993-11-02 | Basf Aktiengesellschaft | Carboxamides, their preparation and their use as herbicides |
| US5378703A (en) * | 1990-04-09 | 1995-01-03 | Alcon Laboratories, Inc. | Sulfonamides useful as carbonic anhydrase inhibitors |
| US5571810A (en) * | 1990-06-11 | 1996-11-05 | Fujisawa Pharmaceutical Co., Ltd. | Thiophene derivatives |
| WO1998002430A1 (en) * | 1996-07-11 | 1998-01-22 | Pfizer Pharmaceuticals Inc. | Pyridylpyrrole compounds useful as interleukin- and tnf antagonists |
| PT853083E (pt) * | 1997-01-06 | 2001-12-28 | Pfizer | Composto de piridilfurano e piridiltiofeno e sua utilizacao farmaceutica |
| US6037340A (en) | 1997-05-28 | 2000-03-14 | Cadus Pharmaceutical Corporation | Synthesis and use of thiophene- and pyrrole-based heteroaromatic compounds |
| DE19744026A1 (de) * | 1997-10-06 | 1999-04-08 | Hoechst Marion Roussel De Gmbh | Pyrazol-Derivate, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| WO1999046244A1 (en) | 1998-03-12 | 1999-09-16 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (ptpases) |
| HN2000000051A (es) | 1999-05-19 | 2001-02-02 | Pfizer Prod Inc | Derivados heterociclicos utiles como agentes anticancerosos |
| US6414013B1 (en) | 2000-06-19 | 2002-07-02 | Pharmacia & Upjohn S.P.A. | Thiophene compounds, process for preparing the same, and pharmaceutical compositions containing the same background of the invention |
| JP2004523476A (ja) * | 2000-10-12 | 2004-08-05 | スミスクライン・ビーチャム・コーポレイション | ＮＦ−κＢ阻害剤 |
| US20040024047A1 (en) * | 2001-10-12 | 2004-02-05 | Callahan James F. | Nf-kb inhibitors |
| SE0102616D0 (sv) * | 2001-07-25 | 2001-07-25 | Astrazeneca Ab | Novel compounds |
| SE0102617D0 (sv) * | 2001-07-25 | 2001-07-25 | Astrazeneca Ab | Novel compounds |
| DE60229975D1 (de) * | 2001-10-04 | 2009-01-02 | Smithkline Beecham Corp | Nf-kb-inhibitoren |
| SE0300091D0 (sv) * | 2003-01-15 | 2003-01-15 | Astrazeneca Ab | Novel compounds |
-
2000
- 2000-02-12 GB GBGB0003154.2A patent/GB0003154D0/en not_active Ceased
-
2001
- 2001-02-07 AT AT01902951T patent/ATE266019T1/de active
- 2001-02-07 MX MXPA02007734A patent/MXPA02007734A/es active IP Right Grant
- 2001-02-07 EP EP01902951A patent/EP1261600B1/en not_active Expired - Lifetime
- 2001-02-07 AU AU30705/01A patent/AU781047B2/en not_active Ceased
- 2001-02-07 NZ NZ519947A patent/NZ519947A/en not_active IP Right Cessation
- 2001-02-07 DE DE60103132T patent/DE60103132T2/de not_active Expired - Lifetime
- 2001-02-07 BR BR0108143-8A patent/BR0108143A/pt not_active Application Discontinuation
- 2001-02-07 TR TR2004/01962T patent/TR200401962T4/xx unknown
- 2001-02-07 PT PT01902951T patent/PT1261600E/pt unknown
- 2001-02-07 US US09/868,884 patent/US7358376B2/en not_active Expired - Fee Related
- 2001-02-07 WO PCT/SE2001/000248 patent/WO2001058890A1/en not_active Ceased
- 2001-02-07 ES ES01902951T patent/ES2218376T3/es not_active Expired - Lifetime
- 2001-02-07 CA CA2396824A patent/CA2396824C/en not_active Expired - Fee Related
- 2001-02-07 KR KR1020027010124A patent/KR100738165B1/ko not_active Expired - Fee Related
- 2001-02-07 JP JP2001558440A patent/JP4812999B2/ja not_active Expired - Fee Related
- 2001-02-07 DK DK01902951T patent/DK1261600T3/da active
- 2001-02-07 IL IL15048201A patent/IL150482A0/xx active IP Right Grant
- 2001-02-07 CN CNB018046606A patent/CN1243747C/zh not_active Expired - Fee Related
-
2002
- 2002-06-27 IL IL150482A patent/IL150482A/en not_active IP Right Cessation
- 2002-07-02 ZA ZA200205300A patent/ZA200205300B/en unknown
- 2002-08-09 NO NO20023786A patent/NO327741B1/no not_active IP Right Cessation
-
2007
- 2007-12-03 US US11/949,273 patent/US20090181962A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| PT1261600E (pt) | 2004-08-31 |
| NO20023786L (no) | 2002-09-23 |
| CN1425012A (zh) | 2003-06-18 |
| DE60103132D1 (de) | 2004-06-09 |
| US7358376B2 (en) | 2008-04-15 |
| US20090181962A1 (en) | 2009-07-16 |
| IL150482A (en) | 2006-08-01 |
| NO327741B1 (no) | 2009-09-14 |
| ZA200205300B (en) | 2003-10-02 |
| AU3070501A (en) | 2001-08-20 |
| CA2396824A1 (en) | 2001-08-16 |
| EP1261600B1 (en) | 2004-05-06 |
| CN1243747C (zh) | 2006-03-01 |
| ATE266019T1 (de) | 2004-05-15 |
| DK1261600T3 (da) | 2004-08-16 |
| NO20023786D0 (no) | 2002-08-09 |
| KR20030005183A (ko) | 2003-01-17 |
| KR100738165B1 (ko) | 2007-07-10 |
| WO2001058890A1 (en) | 2001-08-16 |
| GB0003154D0 (en) | 2000-04-05 |
| BR0108143A (pt) | 2003-01-21 |
| NZ519947A (en) | 2004-05-28 |
| US20020107252A1 (en) | 2002-08-08 |
| DE60103132T2 (de) | 2005-05-12 |
| JP4812999B2 (ja) | 2011-11-09 |
| MXPA02007734A (es) | 2002-10-11 |
| TR200401962T4 (tr) | 2004-09-21 |
| EP1261600A1 (en) | 2002-12-04 |
| IL150482A0 (en) | 2002-12-01 |
| JP2003522766A (ja) | 2003-07-29 |
| ES2218376T3 (es) | 2004-11-16 |
| AU781047B2 (en) | 2005-05-05 |
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