DE60023853T2 - Aromatische heterozyklische verbindungen als antientzündungwirkstoffe - Google Patents
Aromatische heterozyklische verbindungen als antientzündungwirkstoffe Download PDFInfo
- Publication number
- DE60023853T2 DE60023853T2 DE60023853T DE60023853T DE60023853T2 DE 60023853 T2 DE60023853 T2 DE 60023853T2 DE 60023853 T DE60023853 T DE 60023853T DE 60023853 T DE60023853 T DE 60023853T DE 60023853 T2 DE60023853 T2 DE 60023853T2
- Authority
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- Germany
- Prior art keywords
- urea
- tert
- butyl
- naphthalen
- ethoxy
- 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 - Lifetime
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- 239000013543 active substance Substances 0.000 title 1
- 230000003110 anti-inflammatory effect Effects 0.000 title 1
- 150000002391 heterocyclic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 73
- 238000000034 method Methods 0.000 claims abstract description 60
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 49
- 201000010099 disease Diseases 0.000 claims abstract description 45
- 230000008569 process Effects 0.000 claims abstract description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 63
- -1 cyclopentanyl Chemical group 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 102000004127 Cytokines Human genes 0.000 claims description 40
- 108090000695 Cytokines Proteins 0.000 claims description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- 239000004202 carbamide Substances 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000001624 naphthyl group Chemical group 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 230000002757 inflammatory effect Effects 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 230000001154 acute effect Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 230000006378 damage Effects 0.000 claims description 10
- 208000014674 injury Diseases 0.000 claims description 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 9
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 9
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 8
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 150000004982 aromatic amines Chemical class 0.000 claims description 7
- 125000003435 aroyl group Chemical group 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 210000000440 neutrophil Anatomy 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 5
- 206010040070 Septic Shock Diseases 0.000 claims description 5
- 208000027418 Wounds and injury Diseases 0.000 claims description 5
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical group O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 230000008733 trauma Effects 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 3
- NQPJDJVGBDHCAD-UHFFFAOYSA-N 1,3-diazinan-2-one Chemical group OC1=NCCCN1 NQPJDJVGBDHCAD-UHFFFAOYSA-N 0.000 claims description 3
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 3
- QYCGBAJADAGLLK-UHFFFAOYSA-N 1-(cyclohepten-1-yl)cycloheptene Chemical group C1CCCCC=C1C1=CCCCCC1 QYCGBAJADAGLLK-UHFFFAOYSA-N 0.000 claims description 3
- VSIYJQNFMOOGCU-UHFFFAOYSA-N 1-(cyclohexen-1-yl)cyclohexene Chemical group C1CCCC(C=2CCCCC=2)=C1 VSIYJQNFMOOGCU-UHFFFAOYSA-N 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 3
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 3
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 3
- PGWWISXRLLMODG-UHFFFAOYSA-N 5-tert-butyl-3-[[4-[2-(3,4-dimethoxyphenyl)ethoxy]naphthalen-1-yl]carbamoylamino]-n-methyl-1h-pyrrole-2-carboxamide Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC=3C=C(OC)C(OC)=CC=3)=CC=2)=C1C(=O)NC PGWWISXRLLMODG-UHFFFAOYSA-N 0.000 claims description 3
- XALRWHKVUNCXFD-UHFFFAOYSA-N 5-tert-butyl-3-[[4-[2-(3,4-dimethoxyphenyl)ethoxy]naphthalen-1-yl]carbamoylamino]-n-methylthiophene-2-carboxamide Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC=3C=C(OC)C(OC)=CC=3)=CC=2)=C1C(=O)NC XALRWHKVUNCXFD-UHFFFAOYSA-N 0.000 claims description 3
- DBINKLWMKFHELZ-RTBURBONSA-N 5-tert-butyl-3-[[4-[2-[(2r,6r)-2,6-dimethylmorpholin-4-yl]ethoxy]naphthalen-1-yl]carbamoylamino]-n-methylthiophene-2-carboxamide Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3C[C@@H](C)O[C@H](C)C3)=CC=2)=C1C(=O)NC DBINKLWMKFHELZ-RTBURBONSA-N 0.000 claims description 3
- ZFBZFJLVVHBHEP-UHFFFAOYSA-N 5-tert-butyl-3-[[4-[2-[2-[(dimethylamino)methyl]-3,3-dimethylmorpholin-4-yl]ethoxy]naphthalen-1-yl]carbamoylamino]-n-methylthiophene-2-carboxamide Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3C(C(CN(C)C)OCC3)(C)C)=CC=2)=C1C(=O)NC ZFBZFJLVVHBHEP-UHFFFAOYSA-N 0.000 claims description 3
- VSNYNOHBCOGJTN-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxamide Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCOCC3)=CC=2)=C1C(=O)NC VSNYNOHBCOGJTN-UHFFFAOYSA-N 0.000 claims description 3
- NKIIHOYVIVWGIQ-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]carbamoylamino]thiophene-2-carboxamide Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCOCC3)=CC=2)=C1C(=O)NC NKIIHOYVIVWGIQ-UHFFFAOYSA-N 0.000 claims description 3
- YORFITFIMBVABT-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-(pyridin-4-ylmethoxy)naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxamide Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCC=3C=CN=CC=3)=CC=2)=C1C(=O)NC YORFITFIMBVABT-UHFFFAOYSA-N 0.000 claims description 3
- PGFKYUQJHNYVPG-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-(pyridin-4-ylmethoxy)naphthalen-1-yl]carbamoylamino]thiophene-2-carboxamide Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCC=3C=CN=CC=3)=CC=2)=C1C(=O)NC PGFKYUQJHNYVPG-UHFFFAOYSA-N 0.000 claims description 3
- YWEOIZSNUGQTGA-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-[2-(1-oxo-1,4-thiazinan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxamide Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCS(=O)CC3)=CC=2)=C1C(=O)NC YWEOIZSNUGQTGA-UHFFFAOYSA-N 0.000 claims description 3
- MJOCHOPTSYVKSJ-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-[2-(1-oxothiolan-3-yl)ethoxy]naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxamide Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC3CS(=O)CC3)=CC=2)=C1C(=O)NC MJOCHOPTSYVKSJ-UHFFFAOYSA-N 0.000 claims description 3
- VGZGHNQNNYORPX-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-[2-(1-oxothiolan-3-yl)ethoxy]naphthalen-1-yl]carbamoylamino]thiophene-2-carboxamide Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC3CS(=O)CC3)=CC=2)=C1C(=O)NC VGZGHNQNNYORPX-UHFFFAOYSA-N 0.000 claims description 3
- VDLCFWXMZIWBKJ-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-[2-(oxan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxamide Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC3CCOCC3)=CC=2)=C1C(=O)NC VDLCFWXMZIWBKJ-UHFFFAOYSA-N 0.000 claims description 3
- NXGOYFFGLZUXHT-UHFFFAOYSA-N 5-tert-butyl-n-methyl-3-[[4-[2-(oxan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]thiophene-2-carboxamide Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC3CCOCC3)=CC=2)=C1C(=O)NC NXGOYFFGLZUXHT-UHFFFAOYSA-N 0.000 claims description 3
- 208000000094 Chronic Pain Diseases 0.000 claims description 3
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims description 3
- 206010018366 Glomerulonephritis acute Diseases 0.000 claims description 3
- 201000009906 Meningitis Diseases 0.000 claims description 3
- 206010051606 Necrotising colitis Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical group C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 3
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 3
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 3
- 231100000851 acute glomerulonephritis Toxicity 0.000 claims description 3
- 208000005298 acute pain Diseases 0.000 claims description 3
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 claims description 3
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 claims description 3
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical group OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 3
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 238000001631 haemodialysis Methods 0.000 claims description 3
- 230000000322 hemodialysis Effects 0.000 claims description 3
- 208000028774 intestinal disease Diseases 0.000 claims description 3
- 125000005647 linker group Chemical group 0.000 claims description 3
- AFSRNVKUVDCLSW-UHFFFAOYSA-N methyl 5-tert-butyl-1-methyl-3-[[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]carbamoylamino]pyrrole-2-carboxylate Chemical compound C1=C(C(C)(C)C)N(C)C(C(=O)OC)=C1NC(=O)NC(C1=CC=CC=C11)=CC=C1OCCN1CCOCC1 AFSRNVKUVDCLSW-UHFFFAOYSA-N 0.000 claims description 3
- HGLZTHSWAWGVLG-UHFFFAOYSA-N methyl 5-tert-butyl-1-methyl-3-[[4-[2-(1-oxo-1,4-thiazinan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]pyrrole-2-carboxylate Chemical compound C1=C(C(C)(C)C)N(C)C(C(=O)OC)=C1NC(=O)NC(C1=CC=CC=C11)=CC=C1OCCN1CCS(=O)CC1 HGLZTHSWAWGVLG-UHFFFAOYSA-N 0.000 claims description 3
- UBEHIWRIYATGFG-UHFFFAOYSA-N methyl 5-tert-butyl-1-methyl-3-[[4-[2-(1-oxothiolan-3-yl)ethoxy]naphthalen-1-yl]carbamoylamino]pyrrole-2-carboxylate Chemical compound C1=C(C(C)(C)C)N(C)C(C(=O)OC)=C1NC(=O)NC(C1=CC=CC=C11)=CC=C1OCCC1CS(=O)CC1 UBEHIWRIYATGFG-UHFFFAOYSA-N 0.000 claims description 3
- CZPSDXRGZVEKMW-UHFFFAOYSA-N methyl 5-tert-butyl-2-[[4-[2-(1-oxo-1,4-thiazinan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]thiophene-3-carboxylate Chemical compound C1=C(C(C)(C)C)SC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCS(=O)CC3)=CC=2)=C1C(=O)OC CZPSDXRGZVEKMW-UHFFFAOYSA-N 0.000 claims description 3
- IDTITQIMVNKGAR-UHFFFAOYSA-N methyl 5-tert-butyl-2-[[4-[2-(oxan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]thiophene-3-carboxylate Chemical compound C1=C(C(C)(C)C)SC(NC(=O)NC=2C3=CC=CC=C3C(OCCC3CCOCC3)=CC=2)=C1C(=O)OC IDTITQIMVNKGAR-UHFFFAOYSA-N 0.000 claims description 3
- AKOLQLJOAIIHPN-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(2-imidazol-1-ylethoxy)naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3C=NC=C3)=CC=2)=C1C(=O)OC AKOLQLJOAIIHPN-UHFFFAOYSA-N 0.000 claims description 3
- MSARKUQLCOSNJQ-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(2-imidazol-1-ylethoxy)naphthalen-1-yl]carbamoylamino]thiophene-2-carboxylate Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3C=NC=C3)=CC=2)=C1C(=O)OC MSARKUQLCOSNJQ-UHFFFAOYSA-N 0.000 claims description 3
- SNTFQLGVKIFINZ-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]carbamoylamino]thiophene-2-carboxylate Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCOCC3)=CC=2)=C1C(=O)OC SNTFQLGVKIFINZ-UHFFFAOYSA-N 0.000 claims description 3
- JLGOWJGNJIUPET-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(pyridin-4-ylmethoxy)naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCC=3C=CN=CC=3)=CC=2)=C1C(=O)OC JLGOWJGNJIUPET-UHFFFAOYSA-N 0.000 claims description 3
- YDKOVAGUKFXVCU-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(pyridin-4-ylmethoxy)naphthalen-1-yl]carbamoylamino]thiophene-2-carboxylate Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCC=3C=CN=CC=3)=CC=2)=C1C(=O)OC YDKOVAGUKFXVCU-UHFFFAOYSA-N 0.000 claims description 3
- UYTZCZYZLBOCQR-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-[2-(1-oxo-1,4-thiazinan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCS(=O)CC3)=CC=2)=C1C(=O)OC UYTZCZYZLBOCQR-UHFFFAOYSA-N 0.000 claims description 3
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- XEEUQQZATLDEFH-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(3-morpholin-4-ylprop-1-ynyl)naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(C#CCN3CCOCC3)=CC=2)=C1C(=O)OC XEEUQQZATLDEFH-UHFFFAOYSA-N 0.000 description 1
- DSLLLNHXHCCEKH-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(3-morpholin-4-ylprop-1-ynyl)naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(C#CCN3CCOCC3)=CC=2)=C1C(=O)OC DSLLLNHXHCCEKH-UHFFFAOYSA-N 0.000 description 1
- HOODISBOCHYTSS-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(3-morpholin-4-ylprop-1-ynyl)naphthalen-1-yl]carbamoylamino]thiophene-2-carboxylate Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(C#CCN3CCOCC3)=CC=2)=C1C(=O)OC HOODISBOCHYTSS-UHFFFAOYSA-N 0.000 description 1
- ZKVFCYMKHIMQSO-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(3-morpholin-4-ylpropyl)naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(CCCN3CCOCC3)=CC=2)=C1C(=O)OC ZKVFCYMKHIMQSO-UHFFFAOYSA-N 0.000 description 1
- VIPIVTXVLSVCDC-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(3-pyridin-4-ylpropoxy)naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCCC=3C=CN=CC=3)=CC=2)=C1C(=O)OC VIPIVTXVLSVCDC-UHFFFAOYSA-N 0.000 description 1
- ZTYZAOMKAJGETR-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(morpholin-4-ylmethyl)naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(CN3CCOCC3)=CC=2)=C1C(=O)OC ZTYZAOMKAJGETR-UHFFFAOYSA-N 0.000 description 1
- JYCFKDCOSXEMGH-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(morpholin-4-ylmethyl)naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(CN3CCOCC3)=CC=2)=C1C(=O)OC JYCFKDCOSXEMGH-UHFFFAOYSA-N 0.000 description 1
- CZCLDIKFKUEVAB-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-(morpholin-4-ylmethyl)naphthalen-1-yl]carbamoylamino]thiophene-2-carboxylate Chemical compound S1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(CN3CCOCC3)=CC=2)=C1C(=O)OC CZCLDIKFKUEVAB-UHFFFAOYSA-N 0.000 description 1
- XGJWMIUOEACTLX-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-[2-(1-oxo-1,4-thiazinan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCS(=O)CC3)=CC=2)=C1C(=O)OC XGJWMIUOEACTLX-UHFFFAOYSA-N 0.000 description 1
- SETOZDVDBPYHJE-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-[2-(1-oxothiolan-3-yl)ethoxy]naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC3CS(=O)CC3)=CC=2)=C1C(=O)OC SETOZDVDBPYHJE-UHFFFAOYSA-N 0.000 description 1
- JLYNQVAPMKQHRU-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-[2-(3,4-dimethoxyphenyl)ethoxy]naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC=3C=C(OC)C(OC)=CC=3)=CC=2)=C1C(=O)OC JLYNQVAPMKQHRU-UHFFFAOYSA-N 0.000 description 1
- MSQNEIVZNUBRQI-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-[2-(oxan-4-yl)ethoxy]naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCC3CCOCC3)=CC=2)=C1C(=O)OC MSQNEIVZNUBRQI-UHFFFAOYSA-N 0.000 description 1
- SUONKLRVFFWDGG-RTBURBONSA-N methyl 5-tert-butyl-3-[[4-[2-[(2r,6r)-2,6-dimethylmorpholin-4-yl]ethoxy]naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3C[C@@H](C)O[C@H](C)C3)=CC=2)=C1C(=O)OC SUONKLRVFFWDGG-RTBURBONSA-N 0.000 description 1
- SUONKLRVFFWDGG-KDURUIRLSA-N methyl 5-tert-butyl-3-[[4-[2-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethoxy]naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3C[C@@H](C)O[C@@H](C)C3)=CC=2)=C1C(=O)OC SUONKLRVFFWDGG-KDURUIRLSA-N 0.000 description 1
- PFOXYNDIZVKXCZ-KDURUIRLSA-N methyl 5-tert-butyl-3-[[4-[2-[(2s,6r)-2,6-dimethylmorpholin-4-yl]ethoxy]naphthalen-1-yl]carbamoylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C(C(C)(C)C)=CC(NC(=O)NC=2C3=CC=CC=C3C(OCCN3C[C@@H](C)O[C@@H](C)C3)=CC=2)=C1C(=O)OC PFOXYNDIZVKXCZ-KDURUIRLSA-N 0.000 description 1
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- NMPRBLZQKDEWII-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-[2-[2-(methoxymethyl)morpholin-4-yl]ethoxy]naphthalen-1-yl]carbamoylamino]furan-2-carboxylate Chemical compound C1COC(COC)CN1CCOC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=C(C(=O)OC)OC(C(C)(C)C)=C1 NMPRBLZQKDEWII-UHFFFAOYSA-N 0.000 description 1
- PXKSVVDZFTUQQK-UHFFFAOYSA-N methyl 5-tert-butyl-3-[[4-[2-[2-(methoxymethyl)morpholin-4-yl]ethoxy]naphthalen-1-yl]carbamoylamino]thiophene-2-carboxylate Chemical compound C1COC(COC)CN1CCOC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=C(C(=O)OC)SC(C(C)(C)C)=C1 PXKSVVDZFTUQQK-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12414799P | 1999-03-12 | 1999-03-12 | |
| US124147P | 1999-03-12 | ||
| PCT/US2000/002008 WO2000055152A1 (en) | 1999-03-12 | 2000-01-31 | Aromatic heterocyclic compounds as anti-inflammatory agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60023853D1 DE60023853D1 (de) | 2005-12-15 |
| DE60023853T2 true DE60023853T2 (de) | 2006-05-24 |
Family
ID=22413056
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60023853T Expired - Lifetime DE60023853T2 (de) | 1999-03-12 | 2000-01-31 | Aromatische heterozyklische verbindungen als antientzündungwirkstoffe |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US6297381B1 (enExample) |
| EP (1) | EP1163236B1 (enExample) |
| JP (1) | JP2002539206A (enExample) |
| AT (1) | ATE309237T1 (enExample) |
| CA (1) | CA2361998C (enExample) |
| DE (1) | DE60023853T2 (enExample) |
| ES (1) | ES2251360T3 (enExample) |
| MX (1) | MXPA01009077A (enExample) |
| WO (1) | WO2000055152A1 (enExample) |
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| US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| EP1158985B1 (en) | 1999-01-13 | 2011-12-28 | Bayer HealthCare LLC | OMEGA-CARBOXY ARYL SUBSTITUTED DIPHENYL UREAS AS p38 KINASE INHIBITORS |
| EP1140840B1 (en) * | 1999-01-13 | 2006-03-22 | Bayer Pharmaceuticals Corp. | -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| UA73492C2 (en) * | 1999-01-19 | 2005-08-15 | Aromatic heterocyclic compounds as antiinflammatory agents | |
| MXPA02000314A (es) * | 1999-07-09 | 2004-06-22 | Boehringer Ingelheim Pharma | Proceso novedoso para la sintesis de compuestos de urea substituidos con heteroarilo. |
| CA2389360C (en) | 1999-11-16 | 2008-06-03 | Steffen Breitfelder | Urea derivatives as anti-inflammatory agents |
| US7235576B1 (en) | 2001-01-12 | 2007-06-26 | Bayer Pharmaceuticals Corporation | Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
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| KR100594377B1 (ko) * | 2003-05-17 | 2006-06-30 | 한국생명공학연구원 | 항염증 활성을 갖는 신규 2-옥소-피페리딘 유도체(ⅰ)화합물, 이의 제조방법 및 이를 포함하는 염증 질환의치료를 위한 조성물 |
| DE602004011340T2 (de) | 2003-05-20 | 2008-11-06 | Bayer Healthcare Llc | Diaryl-harnstoffe mit kinasehemmender wirkung |
| NZ544920A (en) | 2003-07-23 | 2009-11-27 | Bayer Healthcare Llc | 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide and metabolites for the treatment and prevention of diseases and conditions |
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-
2000
- 2000-01-31 DE DE60023853T patent/DE60023853T2/de not_active Expired - Lifetime
- 2000-01-31 AT AT00909993T patent/ATE309237T1/de active
- 2000-01-31 CA CA002361998A patent/CA2361998C/en not_active Expired - Fee Related
- 2000-01-31 JP JP2000605581A patent/JP2002539206A/ja active Pending
- 2000-01-31 EP EP00909993A patent/EP1163236B1/en not_active Expired - Lifetime
- 2000-01-31 MX MXPA01009077A patent/MXPA01009077A/es not_active IP Right Cessation
- 2000-01-31 ES ES00909993T patent/ES2251360T3/es not_active Expired - Lifetime
- 2000-01-31 WO PCT/US2000/002008 patent/WO2000055152A1/en not_active Ceased
- 2000-02-14 US US09/503,385 patent/US6297381B1/en not_active Expired - Lifetime
- 2000-11-20 US US09/716,351 patent/US6476023B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2361998C (en) | 2009-04-07 |
| JP2002539206A (ja) | 2002-11-19 |
| US6476023B1 (en) | 2002-11-05 |
| MXPA01009077A (es) | 2002-03-27 |
| DE60023853D1 (de) | 2005-12-15 |
| CA2361998A1 (en) | 2000-09-21 |
| US6297381B1 (en) | 2001-10-02 |
| WO2000055152A1 (en) | 2000-09-21 |
| ES2251360T3 (es) | 2006-05-01 |
| ATE309237T1 (de) | 2005-11-15 |
| EP1163236A1 (en) | 2001-12-19 |
| EP1163236B1 (en) | 2005-11-09 |
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