PT1784183E - Processos para a preparação de derivados de isotiazole - Google Patents
Processos para a preparação de derivados de isotiazole Download PDFInfo
- Publication number
- PT1784183E PT1784183E PT05778840T PT05778840T PT1784183E PT 1784183 E PT1784183 E PT 1784183E PT 05778840 T PT05778840 T PT 05778840T PT 05778840 T PT05778840 T PT 05778840T PT 1784183 E PT1784183 E PT 1784183E
- Authority
- PT
- Portugal
- Prior art keywords
- aryl
- isothiazole
- ureido
- carboxylic acid
- benzyloxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 39
- 238000002360 preparation method Methods 0.000 title claims description 25
- 150000003854 isothiazoles Chemical class 0.000 title description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 254
- 125000003118 aryl group Chemical group 0.000 claims description 226
- -1 C1 -C10 alkyl Chemical group 0.000 claims description 160
- 150000001875 compounds Chemical class 0.000 claims description 113
- 125000000217 alkyl group Chemical group 0.000 claims description 108
- 229910052760 oxygen Inorganic materials 0.000 claims description 84
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 80
- 125000004434 sulfur atom Chemical group 0.000 claims description 80
- 125000001424 substituent group Chemical group 0.000 claims description 72
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 54
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 53
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 50
- 125000004122 cyclic group Chemical group 0.000 claims description 50
- 125000005842 heteroatom Chemical group 0.000 claims description 47
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 45
- 239000002904 solvent Substances 0.000 claims description 38
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 37
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 125000004432 carbon atom Chemical group C* 0.000 claims description 30
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 28
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 229910021529 ammonia Inorganic materials 0.000 claims description 18
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 15
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 229940002612 prodrug Drugs 0.000 claims description 14
- 239000000651 prodrug Substances 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 150000004702 methyl esters Chemical class 0.000 claims description 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
- PJXPORIRXYJDLD-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylic acid Chemical compound S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)O)=C1NC(=O)NCCCCN1CCCC1 PJXPORIRXYJDLD-UHFFFAOYSA-N 0.000 claims description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 125000003367 polycyclic group Chemical group 0.000 claims description 5
- MLTRVXNMTIBDJI-UHFFFAOYSA-N 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[4-[ethyl(2-hydroxyethyl)amino]butylcarbamoylamino]-1,2-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=C(NC(=O)NCCCCN(CCO)CC)SN=C1OCC1=C(F)C=C(Cl)C=C1F MLTRVXNMTIBDJI-UHFFFAOYSA-N 0.000 claims description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
- FLTUSYTWLHGKSB-UHFFFAOYSA-N 5-[3-(4-methylpiperazin-1-yl)propylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylic acid Chemical compound C1CN(C)CCN1CCCNC(=O)NC1=C(C(O)=O)C(OCC=2C(=C(F)C(C)=CC=2F)F)=NS1 FLTUSYTWLHGKSB-UHFFFAOYSA-N 0.000 claims description 4
- NZLRJJCXOVYZRF-UHFFFAOYSA-N 5-[4-[bis(2-hydroxyethyl)amino]butylcarbamoylamino]-3-[(2,6-difluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylic acid Chemical compound FC1=CC(C)=CC(F)=C1COC1=NSC(NC(=O)NCCCCN(CCO)CCO)=C1C(O)=O NZLRJJCXOVYZRF-UHFFFAOYSA-N 0.000 claims description 4
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims description 4
- QBRJZYJMHZZQKY-UHFFFAOYSA-N methyl 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-methylsulfonyl-1,2-thiazole-4-carboxylate Chemical group S1C(S(C)(=O)=O)=C(C(=O)OC)C(OCC=2C(=CC(Br)=CC=2F)F)=N1 QBRJZYJMHZZQKY-UHFFFAOYSA-N 0.000 claims description 4
- KGKURLCJVMTUAH-UHFFFAOYSA-N methyl 5-amino-3-[(4-bromo-2,6-difluorophenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical group COC(=O)C1=C(N)SN=C1OCC1=C(F)C=C(Br)C=C1F KGKURLCJVMTUAH-UHFFFAOYSA-N 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- HXHAJRMTJXHJJZ-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1 HXHAJRMTJXHJJZ-UHFFFAOYSA-N 0.000 claims description 3
- UOHVFUKYCPCDMK-UHFFFAOYSA-N 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-[3-[ethyl(2-hydroxyethyl)amino]propylcarbamoylamino]-1,2-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=C(NC(=O)NCCCN(CCO)CC)SN=C1OCC1=C(F)C=C(Cl)C(F)=C1F UOHVFUKYCPCDMK-UHFFFAOYSA-N 0.000 claims description 3
- NKDLZDBLODZAES-UHFFFAOYSA-N 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-[4-[2-(hydroxymethyl)pyrrolidin-1-yl]butylcarbamoylamino]-1,2-thiazole-4-carboxylic acid Chemical compound OCC1CCCN1CCCCNC(=O)NC1=C(C(O)=O)C(OCC=2C(=C(F)C(Cl)=CC=2F)F)=NS1 NKDLZDBLODZAES-UHFFFAOYSA-N 0.000 claims description 3
- NYYQETQHPXRWLV-UHFFFAOYSA-N 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[2-(1-methylpyrrolidin-2-yl)ethylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound CN1CCCC1CCNC(=O)NC1=C(C(N)=O)C(OCC=2C(=CC(Cl)=CC=2F)F)=NS1 NYYQETQHPXRWLV-UHFFFAOYSA-N 0.000 claims description 3
- ZDEFKACGJVBKCO-UHFFFAOYSA-N 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[3-(4-methylpiperazin-1-yl)propylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound C1CN(C)CCN1CCCNC(=O)NC1=C(C(N)=O)C(OCC=2C(=CC(Cl)=CC=2F)F)=NS1 ZDEFKACGJVBKCO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- GAEFKHUAINDYPU-UHFFFAOYSA-N 5-[4-(4-methylpiperazin-1-yl)butylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylic acid Chemical compound C1CN(C)CCN1CCCCNC(=O)NC1=C(C(O)=O)C(OCC=2C(=C(F)C(C)=CC=2F)F)=NS1 GAEFKHUAINDYPU-UHFFFAOYSA-N 0.000 claims description 3
- CDXWXGJLRJUYAK-UHFFFAOYSA-N 5-[4-[4-(2-hydroxyethyl)piperazin-1-yl]butylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylic acid Chemical compound FC1=C(F)C(C)=CC(F)=C1COC1=NSC(NC(=O)NCCCCN2CCN(CCO)CC2)=C1C(O)=O CDXWXGJLRJUYAK-UHFFFAOYSA-N 0.000 claims description 3
- RTSXOONRXMLUQC-UHFFFAOYSA-N 5-[4-[ethyl(2-hydroxyethyl)amino]butylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=C(NC(=O)NCCCCN(CCO)CC)SN=C1OCC1=C(F)C=C(C)C(F)=C1F RTSXOONRXMLUQC-UHFFFAOYSA-N 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- WVHXBHFWYRJNKU-UHFFFAOYSA-N methyl 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CCCC1 WVHXBHFWYRJNKU-UHFFFAOYSA-N 0.000 claims description 3
- GRIBVKFHFTZOCK-UHFFFAOYSA-N 3-[(2,5-difluoro-4-methylphenyl)methoxy]-5-[4-(3-hydroxypyrrolidin-1-yl)butylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound C1=C(F)C(C)=CC(F)=C1COC1=NSC(NC(=O)NCCCCN2CC(O)CC2)=C1C(N)=O GRIBVKFHFTZOCK-UHFFFAOYSA-N 0.000 claims description 2
- JGVUZSYKCBQTGT-UHFFFAOYSA-N 3-[(2,5-difluoro-4-methylphenyl)methoxy]-5-[4-[ethyl(2-hydroxyethyl)amino]butylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCCN(CCO)CC)SN=C1OCC1=CC(F)=C(C)C=C1F JGVUZSYKCBQTGT-UHFFFAOYSA-N 0.000 claims description 2
- OIJBFJNKDCYVCY-UHFFFAOYSA-N 3-[(2,5-difluoro-4-methylphenyl)methoxy]-5-[4-[ethyl(2-hydroxyethyl)amino]butylcarbamoylamino]-1,2-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=C(NC(=O)NCCCCN(CCO)CC)SN=C1OCC1=CC(F)=C(C)C=C1F OIJBFJNKDCYVCY-UHFFFAOYSA-N 0.000 claims description 2
- QIMZMNAVSSZUFG-UHFFFAOYSA-N 3-[(2,5-difluoro-4-methylphenyl)methoxy]-5-[6-(dimethylamino)hexylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCCCCN(C)C)SN=C1OCC1=CC(F)=C(C)C=C1F QIMZMNAVSSZUFG-UHFFFAOYSA-N 0.000 claims description 2
- QYQQDBQNTUOFJL-UHFFFAOYSA-N 3-[(2,6-difluoro-4-methylphenyl)methoxy]-5-(3-pyrrolidin-1-ylpropylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound FC1=CC(C)=CC(F)=C1COC1=NSC(NC(=O)NCCCN2CCCC2)=C1C(N)=O QYQQDBQNTUOFJL-UHFFFAOYSA-N 0.000 claims description 2
- ARMSUXIOUXKTQE-UHFFFAOYSA-N 3-[(2,6-difluoro-4-methylphenyl)methoxy]-5-[2-(1-methylpyrrolidin-2-yl)ethylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound CN1CCCC1CCNC(=O)NC1=C(C(N)=O)C(OCC=2C(=CC(C)=CC=2F)F)=NS1 ARMSUXIOUXKTQE-UHFFFAOYSA-N 0.000 claims description 2
- GVJSWBMFVKGXAE-UHFFFAOYSA-N 3-[(2,6-difluoro-4-methylphenyl)methoxy]-5-[3-(dimethylamino)propylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCN(C)C)SN=C1OCC1=C(F)C=C(C)C=C1F GVJSWBMFVKGXAE-UHFFFAOYSA-N 0.000 claims description 2
- HFCXEWPMPAOGBM-UHFFFAOYSA-N 3-[(2-fluoro-4-methylphenyl)methoxy]-5-[3-(4-methylpiperazin-1-yl)propylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound C1CN(C)CCN1CCCNC(=O)NC1=C(C(N)=O)C(OCC=2C(=CC(C)=CC=2)F)=NS1 HFCXEWPMPAOGBM-UHFFFAOYSA-N 0.000 claims description 2
- AMLIAESKGXHWSE-UHFFFAOYSA-N 3-[(2-fluoro-4-methylphenyl)methoxy]-5-[5-(propan-2-ylamino)pentylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCCCNC(C)C)SN=C1OCC1=CC=C(C)C=C1F AMLIAESKGXHWSE-UHFFFAOYSA-N 0.000 claims description 2
- QFICIQKWQFJJMF-UHFFFAOYSA-N 3-[(3-chloro-2,6-difluoro-4-methylphenyl)methoxy]-5-[4-(dimethylamino)butylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCCN(C)C)SN=C1OCC1=C(F)C=C(C)C(Cl)=C1F QFICIQKWQFJJMF-UHFFFAOYSA-N 0.000 claims description 2
- HCYLBNPHRUPOIC-UHFFFAOYSA-N 3-[(4-bromo-2,3,6-trifluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=C(F)C(Br)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1 HCYLBNPHRUPOIC-UHFFFAOYSA-N 0.000 claims description 2
- CRBQHUZGHXBQOI-UHFFFAOYSA-N 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-(4-imidazol-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=C(F)C(Cl)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1C=CN=C1 CRBQHUZGHXBQOI-UHFFFAOYSA-N 0.000 claims description 2
- NKGBEPBSPHYERX-UHFFFAOYSA-N 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-[(3-hydroxy-5-pyrrolidin-1-ylpentyl)carbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=C(F)C(Cl)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCC(O)CCN1CCCC1 NKGBEPBSPHYERX-UHFFFAOYSA-N 0.000 claims description 2
- AVBLJLMYGYPZBD-UHFFFAOYSA-N 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-(4-imidazol-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1C=CN=C1 AVBLJLMYGYPZBD-UHFFFAOYSA-N 0.000 claims description 2
- KBASJCBTQBVBOG-UHFFFAOYSA-N 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1 KBASJCBTQBVBOG-UHFFFAOYSA-N 0.000 claims description 2
- AHTAYKWZFAVPQM-UHFFFAOYSA-N 5-(3-pyrrolidin-1-ylpropylcarbamoylamino)-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound FC1=C(F)C(C)=CC(F)=C1COC1=NSC(NC(=O)NCCCN2CCCC2)=C1C(N)=O AHTAYKWZFAVPQM-UHFFFAOYSA-N 0.000 claims description 2
- PNLQTLDEFBVYHM-UHFFFAOYSA-N 5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound FC1=C(F)C(C)=CC(F)=C1COC1=NSC(NC(=O)NCCCCN2CCCC2)=C1C(N)=O PNLQTLDEFBVYHM-UHFFFAOYSA-N 0.000 claims description 2
- JZKSAVFKXZDXTQ-UHFFFAOYSA-N 5-[(3-hydroxy-5-pyrrolidin-1-ylpentyl)carbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound FC1=C(F)C(C)=CC(F)=C1COC1=NSC(NC(=O)NCCC(O)CCN2CCCC2)=C1C(N)=O JZKSAVFKXZDXTQ-UHFFFAOYSA-N 0.000 claims description 2
- JAPPCINOHTZNJE-UHFFFAOYSA-N 5-[2-(1-methylpyrrolidin-2-yl)ethylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylic acid Chemical compound CN1CCCC1CCNC(=O)NC1=C(C(O)=O)C(OCC=2C(=C(F)C(C)=CC=2F)F)=NS1 JAPPCINOHTZNJE-UHFFFAOYSA-N 0.000 claims description 2
- WXMYZVYEMXHCFL-UHFFFAOYSA-N 5-[3-(dimethylamino)propylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCN(C)C)SN=C1OCC1=C(F)C=C(C)C(F)=C1F WXMYZVYEMXHCFL-UHFFFAOYSA-N 0.000 claims description 2
- ZLGQTFMQIQJIND-UHFFFAOYSA-N 5-[3-(methylamino)propylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCNC)SN=C1OCC1=C(F)C=C(C)C(F)=C1F ZLGQTFMQIQJIND-UHFFFAOYSA-N 0.000 claims description 2
- UFLMPWLAMMMPBH-UHFFFAOYSA-N 5-[3-(propan-2-ylamino)propylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCNC(C)C)SN=C1OCC1=C(F)C=C(C)C(F)=C1F UFLMPWLAMMMPBH-UHFFFAOYSA-N 0.000 claims description 2
- WREMRCJTCVCTHZ-UHFFFAOYSA-N 5-[4-(diethylamino)butylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCCN(CC)CC)SN=C1OCC1=C(F)C=C(C)C(F)=C1F WREMRCJTCVCTHZ-UHFFFAOYSA-N 0.000 claims description 2
- NYNDSKDUQMPEHX-UHFFFAOYSA-N 5-[4-(dimethylamino)butylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)NCCCCN(C)C)SN=C1OCC1=C(F)C=C(C)C(F)=C1F NYNDSKDUQMPEHX-UHFFFAOYSA-N 0.000 claims description 2
- RVEJKOFDHFCLKB-UHFFFAOYSA-N 5-[[3-aminopropyl(methyl)carbamoyl]amino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxamide Chemical compound NC(=O)C1=C(NC(=O)N(CCCN)C)SN=C1OCC1=C(F)C=C(C)C(F)=C1F RVEJKOFDHFCLKB-UHFFFAOYSA-N 0.000 claims description 2
- CPIXYAJJCRHOTJ-UHFFFAOYSA-N methyl 3-[(2,5-difluoro-4-methylphenyl)methoxy]-5-[4-(3-hydroxypyrrolidin-1-yl)butylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(C)=C(F)C=2)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CCC(O)C1 CPIXYAJJCRHOTJ-UHFFFAOYSA-N 0.000 claims description 2
- DFHHYJAARHLEQQ-UHFFFAOYSA-N methyl 3-[(2,5-difluoro-4-methylphenyl)methoxy]-5-[4-[2-(hydroxymethyl)pyrrolidin-1-yl]butylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(C)=C(F)C=2)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CCCC1CO DFHHYJAARHLEQQ-UHFFFAOYSA-N 0.000 claims description 2
- ZVCMMPDTVZXUNC-UHFFFAOYSA-N methyl 3-[(2,5-difluoro-4-methylphenyl)methoxy]-5-[6-(dimethylamino)hexylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1C(NC(=O)NCCCCCCN(C)C)=C(C(=O)OC)C(OCC=2C(=CC(C)=C(F)C=2)F)=N1 ZVCMMPDTVZXUNC-UHFFFAOYSA-N 0.000 claims description 2
- JXGILVIQYAUXGQ-UHFFFAOYSA-N methyl 3-[(2,6-difluoro-4-methylphenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylate Chemical compound N=1SC(NC(=O)NCCCCN2CCCC2)=C(C(=O)OC)C=1OCC1=C(F)C=C(C)C=C1F JXGILVIQYAUXGQ-UHFFFAOYSA-N 0.000 claims description 2
- DQFULOUGRNYPIT-UHFFFAOYSA-N methyl 3-[(2,6-difluoro-4-methylphenyl)methoxy]-5-[(3-hydroxy-5-pyrrolidin-1-ylpentyl)carbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(C)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCC(O)CCN1CCCC1 DQFULOUGRNYPIT-UHFFFAOYSA-N 0.000 claims description 2
- ZMEXDFWCAWIBTI-UHFFFAOYSA-N methyl 3-[(2-fluoro-4-methylphenyl)methoxy]-5-[3-(4-methylpiperazin-1-yl)propylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound N=1SC(NC(=O)NCCCN2CCN(C)CC2)=C(C(=O)OC)C=1OCC1=CC=C(C)C=C1F ZMEXDFWCAWIBTI-UHFFFAOYSA-N 0.000 claims description 2
- AOTNUPAPIGHNCS-UHFFFAOYSA-N methyl 3-[(2-fluoro-4-methylphenyl)methoxy]-5-[5-(propan-2-ylamino)pentylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1C(NC(=O)NCCCCCNC(C)C)=C(C(=O)OC)C(OCC=2C(=CC(C)=CC=2)F)=N1 AOTNUPAPIGHNCS-UHFFFAOYSA-N 0.000 claims description 2
- HCBXWYPSNANGJD-UHFFFAOYSA-N methyl 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=C(F)C(Cl)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CCCC1 HCBXWYPSNANGJD-UHFFFAOYSA-N 0.000 claims description 2
- SHHJPDMWHWCATJ-UHFFFAOYSA-N methyl 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-(4-imidazol-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCCN1C=CN=C1 SHHJPDMWHWCATJ-UHFFFAOYSA-N 0.000 claims description 2
- OXWAWKZUTJKCAD-UHFFFAOYSA-N methyl 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CCCC1 OXWAWKZUTJKCAD-UHFFFAOYSA-N 0.000 claims description 2
- LYKMAZPRKPTOLB-UHFFFAOYSA-N methyl 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[3-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)propylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound COC(=O)C1=C(NC(=O)NCCCN2C3CC(N(C3)C)C2)SN=C1OCC1=C(F)C=C(Cl)C=C1F LYKMAZPRKPTOLB-UHFFFAOYSA-N 0.000 claims description 2
- CPXGXRLEXKZTST-UHFFFAOYSA-N methyl 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[4-[2-(hydroxymethyl)pyrrolidin-1-yl]butylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CCCC1CO CPXGXRLEXKZTST-UHFFFAOYSA-N 0.000 claims description 2
- SCBHXFKLYDJABR-UHFFFAOYSA-N methyl 5-(3-pyrrolidin-1-ylpropylcarbamoylamino)-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound N=1SC(NC(=O)NCCCN2CCCC2)=C(C(=O)OC)C=1OCC1=C(F)C=C(C)C(F)=C1F SCBHXFKLYDJABR-UHFFFAOYSA-N 0.000 claims description 2
- CVUJQFCRESAPAB-UHFFFAOYSA-N methyl 5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound N=1SC(NC(=O)NCCCCN2CCCC2)=C(C(=O)OC)C=1OCC1=C(F)C=C(C)C(F)=C1F CVUJQFCRESAPAB-UHFFFAOYSA-N 0.000 claims description 2
- VBUKUTDXZLGLJK-UHFFFAOYSA-N methyl 5-[(3-hydroxy-5-pyrrolidin-1-ylpentyl)carbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=C(F)C(C)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCC(O)CCN1CCCC1 VBUKUTDXZLGLJK-UHFFFAOYSA-N 0.000 claims description 2
- NXHHPBXWGZXXEJ-UHFFFAOYSA-N methyl 5-[(4-hydroxy-5-piperidin-1-ylpentyl)carbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=C(F)C(C)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCC(O)CN1CCCCC1 NXHHPBXWGZXXEJ-UHFFFAOYSA-N 0.000 claims description 2
- DGTJIZCUMVPCGO-UHFFFAOYSA-N methyl 5-[3-(dimethylamino)propylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound S1C(NC(=O)NCCCN(C)C)=C(C(=O)OC)C(OCC=2C(=C(F)C(C)=CC=2F)F)=N1 DGTJIZCUMVPCGO-UHFFFAOYSA-N 0.000 claims description 2
- CTFFWTVCFNCGMC-UHFFFAOYSA-N methyl 5-[3-(propan-2-ylamino)propylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound S1C(NC(=O)NCCCNC(C)C)=C(C(=O)OC)C(OCC=2C(=C(F)C(C)=CC=2F)F)=N1 CTFFWTVCFNCGMC-UHFFFAOYSA-N 0.000 claims description 2
- HZGXQPTZUGIFPW-UHFFFAOYSA-N methyl 5-[4-(dimethylamino)butylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound S1C(NC(=O)NCCCCN(C)C)=C(C(=O)OC)C(OCC=2C(=C(F)C(C)=CC=2F)F)=N1 HZGXQPTZUGIFPW-UHFFFAOYSA-N 0.000 claims description 2
- DGXJAGGCMLMDSU-UHFFFAOYSA-N 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[4-[2-(hydroxymethyl)piperidin-1-yl]butylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCCC1CO DGXJAGGCMLMDSU-UHFFFAOYSA-N 0.000 claims 2
- KGDHVWRSIDVHLF-UHFFFAOYSA-N 3-[(4-bromo-2,3,6-trifluorophenyl)methoxy]-5-[3-(4-methylpiperazin-1-yl)propylcarbamoylamino]-1,2-thiazole-4-carboxylic acid Chemical compound C1CN(C)CCN1CCCNC(=O)NC1=C(C(O)=O)C(OCC=2C(=C(F)C(Br)=CC=2F)F)=NS1 KGDHVWRSIDVHLF-UHFFFAOYSA-N 0.000 claims 1
- RNBYFZPZEQJLQT-UHFFFAOYSA-N 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-[3-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)propylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound CN1CC2CC1CN2CCCNC(=O)NC(=C1C(N)=O)SN=C1OCC1=C(F)C=C(Cl)C(F)=C1F RNBYFZPZEQJLQT-UHFFFAOYSA-N 0.000 claims 1
- HLWZBOXPCYYJHT-UHFFFAOYSA-N 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-[4-[2-(hydroxymethyl)piperidin-1-yl]butylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=C(F)C(Cl)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCCC1CO HLWZBOXPCYYJHT-UHFFFAOYSA-N 0.000 claims 1
- ZPNJGUBDUYTZLI-UHFFFAOYSA-N 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[4-[2-(hydroxymethyl)pyrrolidin-1-yl]butylcarbamoylamino]-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1CO ZPNJGUBDUYTZLI-UHFFFAOYSA-N 0.000 claims 1
- NWMFTCUVROERRS-UHFFFAOYSA-N 3-[4-[ethyl(2-hydroxyethyl)amino]butylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-2H-1,2-thiazole-4-carboxamide Chemical compound FC=1C=C(C)C(F)=C(F)C=1COC1(NC(=O)NCCCCN(CCO)CC)NSC=C1C(N)=O NWMFTCUVROERRS-UHFFFAOYSA-N 0.000 claims 1
- 229940125782 compound 2 Drugs 0.000 claims 1
- LCHPYVGLOSGUFS-UHFFFAOYSA-N methyl 3-[(2,6-difluoro-4-methylphenyl)methoxy]-5-(3-pyrrolidin-1-ylpropylcarbamoylamino)-1,2-thiazole-4-carboxylate Chemical compound N=1SC(NC(=O)NCCCN2CCCC2)=C(C(=O)OC)C=1OCC1=C(F)C=C(C)C=C1F LCHPYVGLOSGUFS-UHFFFAOYSA-N 0.000 claims 1
- ZLAJKDDQOYZOGQ-UHFFFAOYSA-N methyl 3-[(2,6-difluoro-4-methylphenyl)methoxy]-5-[3-(dimethylamino)propylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1C(NC(=O)NCCCN(C)C)=C(C(=O)OC)C(OCC=2C(=CC(C)=CC=2F)F)=N1 ZLAJKDDQOYZOGQ-UHFFFAOYSA-N 0.000 claims 1
- LCZJCNBNQPPCNR-UHFFFAOYSA-N methyl 3-[(3-chloro-2,6-difluoro-4-methylphenyl)methoxy]-5-[4-(dimethylamino)butylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1C(NC(=O)NCCCCN(C)C)=C(C(=O)OC)C(OCC=2C(=C(Cl)C(C)=CC=2F)F)=N1 LCZJCNBNQPPCNR-UHFFFAOYSA-N 0.000 claims 1
- BYVKQFFUPQPZHS-UHFFFAOYSA-N methyl 3-[(4-bromo-2,3,6-trifluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=C(F)C(Br)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CCCC1 BYVKQFFUPQPZHS-UHFFFAOYSA-N 0.000 claims 1
- YYRHDUCNMMIWGW-UHFFFAOYSA-N methyl 5-[3-(methylamino)propylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound COC(=O)C1=C(NC(=O)NCCCNC)SN=C1OCC1=C(F)C=C(C)C(F)=C1F YYRHDUCNMMIWGW-UHFFFAOYSA-N 0.000 claims 1
- JTLGSPVHFRXHEH-UHFFFAOYSA-N methyl 5-[4-(diethylamino)butylcarbamoylamino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound COC(=O)C1=C(NC(=O)NCCCCN(CC)CC)SN=C1OCC1=C(F)C=C(C)C(F)=C1F JTLGSPVHFRXHEH-UHFFFAOYSA-N 0.000 claims 1
- ZLEFCSJAIHQAAR-UHFFFAOYSA-N methyl 5-[[3-aminopropyl(methyl)carbamoyl]amino]-3-[(2,3,6-trifluoro-4-methylphenyl)methoxy]-1,2-thiazole-4-carboxylate Chemical compound S1C(NC(=O)N(C)CCCN)=C(C(=O)OC)C(OCC=2C(=C(F)C(C)=CC=2F)F)=N1 ZLEFCSJAIHQAAR-UHFFFAOYSA-N 0.000 claims 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
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- KUHWVZGKCZLWSS-UHFFFAOYSA-N methyl 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-[(3-hydroxy-5-pyrrolidin-1-ylpentyl)carbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=C(F)C(Cl)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCC(O)CCN1CCCC1 KUHWVZGKCZLWSS-UHFFFAOYSA-N 0.000 description 1
- VCLBZKNPAWEHFI-UHFFFAOYSA-N methyl 3-[(4-chloro-2,3,6-trifluorophenyl)methoxy]-5-[3-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)propylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound COC(=O)C1=C(NC(=O)NCCCN2C3CC(N(C3)C)C2)SN=C1OCC1=C(F)C=C(Cl)C(F)=C1F VCLBZKNPAWEHFI-UHFFFAOYSA-N 0.000 description 1
- WDFJVRHIASMJTB-UHFFFAOYSA-N methyl 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[4-(3,4-dihydroxypyrrolidin-1-yl)butylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CC(O)C(O)C1 WDFJVRHIASMJTB-UHFFFAOYSA-N 0.000 description 1
- DWUFOSZUVFTSQA-UHFFFAOYSA-N methyl 3-[(4-chloro-2,6-difluorophenyl)methoxy]-5-[4-[2-(hydroxymethyl)piperidin-1-yl]butylcarbamoylamino]-1,2-thiazole-4-carboxylate Chemical compound S1N=C(OCC=2C(=CC(Cl)=CC=2F)F)C(C(=O)OC)=C1NC(=O)NCCCCN1CCCCC1CO DWUFOSZUVFTSQA-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
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- DMTUQTRZIMTUQV-UHFFFAOYSA-N potassium;ethenylideneazanide Chemical compound [K+].[CH2-]C#N DMTUQTRZIMTUQV-UHFFFAOYSA-N 0.000 description 1
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- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 230000002285 radioactive effect Effects 0.000 description 1
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- 238000012552 review Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical group [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
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- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229910021381 transition metal chloride Inorganic materials 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
- C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60454204P | 2004-08-26 | 2004-08-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1784183E true PT1784183E (pt) | 2012-03-09 |
Family
ID=36000502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT05778840T PT1784183E (pt) | 2004-08-26 | 2005-08-02 | Processos para a preparação de derivados de isotiazole |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US8884025B2 (enExample) |
| EP (1) | EP1784183B1 (enExample) |
| JP (2) | JP5100390B2 (enExample) |
| KR (1) | KR100893977B1 (enExample) |
| CN (1) | CN101043888B (enExample) |
| AR (1) | AR050613A1 (enExample) |
| AT (1) | ATE542533T1 (enExample) |
| AU (1) | AU2005280451B2 (enExample) |
| BR (1) | BRPI0514667A (enExample) |
| CA (1) | CA2578023C (enExample) |
| DK (1) | DK1784183T3 (enExample) |
| ES (1) | ES2378994T3 (enExample) |
| IL (1) | IL181063A0 (enExample) |
| MX (1) | MX2007002246A (enExample) |
| NO (1) | NO20071319L (enExample) |
| PL (1) | PL1784183T3 (enExample) |
| PT (1) | PT1784183E (enExample) |
| RU (1) | RU2349588C2 (enExample) |
| TW (1) | TWI361688B (enExample) |
| WO (1) | WO2006026034A2 (enExample) |
| ZA (1) | ZA200701016B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2007002246A (es) | 2004-08-26 | 2007-04-20 | Pfizer Prod Inc | Procedimientos para la preparacion de derivados de isotiazol. |
| ES2623652T3 (es) | 2011-12-28 | 2017-07-11 | Allergan, Inc. | Derivados de 3-fenil-5-ureidoisotiazol-4-carboximida y 3-amino-5-fenilisotiazol como inhibidores de cinasa |
| CN103833665B (zh) * | 2014-02-24 | 2015-09-23 | 杰达维（上海）医药科技发展有限公司 | 一种新的合成异噻唑的方法 |
| US9353093B2 (en) | 2014-10-07 | 2016-05-31 | Allergan, Inc. | Indole-1-carboxamides as kinase inhibitors |
| US9403803B2 (en) | 2014-10-08 | 2016-08-02 | Allergan, Inc. | Indole-3-carboxamides as kinase inhibitors |
| US9359336B2 (en) | 2014-10-09 | 2016-06-07 | Allergan, Inc. | Heterocycle-substituted pyridyl benzothiophenes as kinase inhibitors |
| US9371314B2 (en) | 2014-10-09 | 2016-06-21 | Allergan, Inc. | Pyridyl benzothiophenes as kinase inhibitors |
| KR20250121146A (ko) * | 2022-12-28 | 2025-08-11 | 비양 테라퓨틱스 컴퍼니 리미티드 | 단백질 티로신 키나제 억제제 및 이의 의약적 용도 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2408234A1 (de) * | 1974-02-21 | 1975-09-04 | Celamerck Gmbh & Co Kg | Isothiazolylharnstoffe |
| US4059433A (en) * | 1976-06-18 | 1977-11-22 | Fmc Corporation | 3-Alkoxyisothiazole derivatives as herbicides |
| IL72093A0 (en) * | 1983-06-20 | 1984-10-31 | Lilly Co Eli | N'-substituted(3-alkyl-5-isothiazolyl)urea derivatives |
| UA60365C2 (uk) * | 1998-06-04 | 2003-10-15 | Пфайзер Продактс Інк. | Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця |
| HN2000000051A (es) * | 1999-05-19 | 2001-02-02 | Pfizer Prod Inc | Derivados heterociclicos utiles como agentes anticancerosos |
| GB0010188D0 (en) * | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
| JP4511352B2 (ja) * | 2002-07-25 | 2010-07-28 | ファイザー・インク | 抗癌薬として有用なイソチアゾール誘導体 |
| US20060035954A1 (en) * | 2004-08-11 | 2006-02-16 | Sharma Padam N | Ammonolysis process for the preparation of intermediates for DPP IV inhibitors |
| MX2007002246A (es) | 2004-08-26 | 2007-04-20 | Pfizer Prod Inc | Procedimientos para la preparacion de derivados de isotiazol. |
-
2005
- 2005-08-02 MX MX2007002246A patent/MX2007002246A/es active IP Right Grant
- 2005-08-02 AT AT05778840T patent/ATE542533T1/de active
- 2005-08-02 ES ES05778840T patent/ES2378994T3/es not_active Expired - Lifetime
- 2005-08-02 AU AU2005280451A patent/AU2005280451B2/en not_active Ceased
- 2005-08-02 CN CN2005800284337A patent/CN101043888B/zh not_active Expired - Fee Related
- 2005-08-02 BR BRPI0514667-4A patent/BRPI0514667A/pt active Search and Examination
- 2005-08-02 US US11/574,046 patent/US8884025B2/en not_active Expired - Fee Related
- 2005-08-02 JP JP2007537876A patent/JP5100390B2/ja not_active Expired - Fee Related
- 2005-08-02 WO PCT/US2005/027398 patent/WO2006026034A2/en not_active Ceased
- 2005-08-02 CA CA2578023A patent/CA2578023C/en not_active Expired - Fee Related
- 2005-08-02 PT PT05778840T patent/PT1784183E/pt unknown
- 2005-08-02 EP EP05778840A patent/EP1784183B1/en not_active Expired - Lifetime
- 2005-08-02 RU RU2007106847/04A patent/RU2349588C2/ru not_active IP Right Cessation
- 2005-08-02 PL PL05778840T patent/PL1784183T3/pl unknown
- 2005-08-02 KR KR1020077004371A patent/KR100893977B1/ko not_active Expired - Fee Related
- 2005-08-02 DK DK05778840.8T patent/DK1784183T3/da active
- 2005-08-22 TW TW094128618A patent/TWI361688B/zh not_active IP Right Cessation
- 2005-08-23 AR ARP050103539A patent/AR050613A1/es not_active Application Discontinuation
-
2007
- 2007-01-30 IL IL181063A patent/IL181063A0/en unknown
- 2007-02-02 ZA ZA200701016A patent/ZA200701016B/xx unknown
- 2007-03-09 NO NO20071319A patent/NO20071319L/no not_active Application Discontinuation
-
2012
- 2012-03-30 JP JP2012079463A patent/JP5498524B2/ja not_active Expired - Fee Related
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2014
- 2014-11-10 US US14/537,093 patent/US9371298B2/en not_active Expired - Fee Related
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