JP6256467B2 - ロイコトリエン生成を阻害するピラゾール誘導体 - Google Patents
ロイコトリエン生成を阻害するピラゾール誘導体 Download PDFInfo
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- JP6256467B2 JP6256467B2 JP2015523172A JP2015523172A JP6256467B2 JP 6256467 B2 JP6256467 B2 JP 6256467B2 JP 2015523172 A JP2015523172 A JP 2015523172A JP 2015523172 A JP2015523172 A JP 2015523172A JP 6256467 B2 JP6256467 B2 JP 6256467B2
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- JP
- Japan
- Prior art keywords
- pyrazol
- ylmethyl
- phenoxy
- yloxy
- pyridin
- 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.)
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- 150000002617 leukotrienes Chemical class 0.000 title claims description 14
- 230000015572 biosynthetic process Effects 0.000 title description 81
- 150000003217 pyrazoles Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 168
- -1 tetrahydro-2H-pyranyl Chemical group 0.000 claims description 106
- 150000003839 salts Chemical class 0.000 claims description 77
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 52
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 239000013543 active substance Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000001475 halogen functional group Chemical group 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- CXWZWZGRKKZXAD-UHFFFAOYSA-N 1-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxynaphthalen-2-yl]methyl]piperidin-4-ol Chemical compound C1CC(O)CCN1CC1=CC=C(C=C(OC=2N=CC(=CC=2)C=2NN=CC=2)C=C2)C2=C1 CXWZWZGRKKZXAD-UHFFFAOYSA-N 0.000 claims description 6
- GICNMVGQMHRWML-IBGZPJMESA-N (5s)-5-[6-[4-(1h-pyrazol-5-yl)phenoxy]quinolin-2-yl]oxypiperidin-2-one Chemical compound C1NC(=O)CC[C@@H]1OC1=CC=C(C=C(OC=2C=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 GICNMVGQMHRWML-IBGZPJMESA-N 0.000 claims description 5
- ZUHUXQHCUKPJGB-UHFFFAOYSA-N 1-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyquinolin-2-yl]methyl]piperidine-4-carbonitrile Chemical compound C1CC(C#N)CCN1CC1=CC=C(C=C(OC=2N=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 ZUHUXQHCUKPJGB-UHFFFAOYSA-N 0.000 claims description 5
- WTHMHZBZBGXDBP-INIZCTEOSA-N 2-[[(2s)-1-methylpyrrolidin-2-yl]methyl]-6-[4-(1h-pyrazol-5-yl)phenoxy]-1h-benzimidazole Chemical compound CN1CCC[C@H]1CC1=NC2=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC=C2N1 WTHMHZBZBGXDBP-INIZCTEOSA-N 0.000 claims description 5
- MSLJKSWJGLRDLB-UHFFFAOYSA-N 2-methyl-6-[4-(1h-pyrazol-5-yl)phenoxy]-3-(pyrrolidin-1-ylmethyl)quinoline Chemical compound C1=C2C=C(CN3CCCC3)C(C)=NC2=CC=C1OC(C=C1)=CC=C1C1=CC=NN1 MSLJKSWJGLRDLB-UHFFFAOYSA-N 0.000 claims description 5
- JYQBTKQNVJPDKY-UHFFFAOYSA-N 3,3-dimethyl-1-[[6-[4-(1h-pyrazol-5-yl)phenoxy]-1h-benzimidazol-2-yl]methyl]pyrrolidin-2-one Chemical compound O=C1C(C)(C)CCN1CC1=NC2=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC=C2N1 JYQBTKQNVJPDKY-UHFFFAOYSA-N 0.000 claims description 5
- RIUAQALOQHBPEX-UHFFFAOYSA-N 4-[1-[[1-[[4-(1h-pyrazol-5-yl)phenyl]methyl]indol-5-yl]methyl]piperidin-4-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1CCN(CC=2C=C3C=CN(CC=4C=CC(=CC=4)C=4NN=CC=4)C3=CC=2)CC1 RIUAQALOQHBPEX-UHFFFAOYSA-N 0.000 claims description 5
- PLENEJQXLLHXNC-UHFFFAOYSA-N 4-[[6-[4-(1h-pyrazol-5-yl)phenoxy]imidazo[1,2-a]pyridin-2-yl]methyl]morpholine Chemical compound C=1N2C=C(OC=3C=CC(=CC=3)C=3NN=CC=3)C=CC2=NC=1CN1CCOCC1 PLENEJQXLLHXNC-UHFFFAOYSA-N 0.000 claims description 5
- FFCYPYCSDQEOJK-UHFFFAOYSA-N 4-[[7-[4-(1h-pyrazol-5-yl)phenoxy]imidazo[1,2-a]pyridin-2-yl]methyl]morpholine Chemical compound C=1N2C=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC2=NC=1CN1CCOCC1 FFCYPYCSDQEOJK-UHFFFAOYSA-N 0.000 claims description 5
- RPYJDDVCKLHVKM-UHFFFAOYSA-N 6-[4-(1h-pyrazol-5-yl)phenoxy]-1h-benzimidazole-2-carboxylic acid Chemical compound C=1C=C2NC(C(=O)O)=NC2=CC=1OC(C=C1)=CC=C1C=1C=CNN=1 RPYJDDVCKLHVKM-UHFFFAOYSA-N 0.000 claims description 5
- YMACOXNLODTFQH-UHFFFAOYSA-N 6-[5-(1h-pyrazol-5-yl)pyrimidin-2-yl]oxy-2-(pyrrolidin-1-ylmethyl)quinoline Chemical compound C=1C=C2C=C(OC=3N=CC(=CN=3)C=3NN=CC=3)C=CC2=NC=1CN1CCCC1 YMACOXNLODTFQH-UHFFFAOYSA-N 0.000 claims description 5
- JTTIRDISEQQCPJ-UHFFFAOYSA-N n-(2-hydroxy-2-methylpropyl)heptanamide Chemical compound CCCCCCC(=O)NCC(C)(C)O JTTIRDISEQQCPJ-UHFFFAOYSA-N 0.000 claims description 5
- YEYFXJQNRNYTBH-UHFFFAOYSA-N n-[1-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxy-2,3-dihydro-1-benzofuran-2-yl]methyl]piperidin-4-yl]acetamide Chemical compound C1CC(NC(=O)C)CCN1CC1OC2=CC(OC=3N=CC(=CC=3)C=3NN=CC=3)=CC=C2C1 YEYFXJQNRNYTBH-UHFFFAOYSA-N 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- LWIVKWCGQULCQD-HNNXBMFYSA-N (5s)-5-[[5-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyindazol-1-yl]methyl]pyrrolidin-2-one Chemical compound N1C(=O)CC[C@H]1CN1C2=CC=C(OC=3N=CC(=CC=3)C=3NN=CC=3)C=C2C=N1 LWIVKWCGQULCQD-HNNXBMFYSA-N 0.000 claims description 4
- GHKGGIKBGMUWIS-KRWDZBQOSA-N (5s)-5-[[6-[4-(1h-pyrazol-5-yl)phenoxy]isoquinolin-1-yl]oxymethyl]pyrrolidin-2-one Chemical compound N1C(=O)CC[C@H]1COC1=NC=CC2=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC=C12 GHKGGIKBGMUWIS-KRWDZBQOSA-N 0.000 claims description 4
- XBBJVLRSZZVPDG-UHFFFAOYSA-N 1-[4-[[6-[4-(1h-pyrazol-5-yl)phenoxy]quinoxalin-2-yl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CN=C(C=C(OC=2C=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 XBBJVLRSZZVPDG-UHFFFAOYSA-N 0.000 claims description 4
- HNLNNEHTIIMTEC-UHFFFAOYSA-N 1-[[1-[[4-(1h-pyrazol-5-yl)phenyl]methyl]indol-5-yl]methyl]azetidin-3-ol Chemical compound C1C(O)CN1CC1=CC=C(N(CC=2C=CC(=CC=2)C=2NN=CC=2)C=C2)C2=C1 HNLNNEHTIIMTEC-UHFFFAOYSA-N 0.000 claims description 4
- YHTSOUMTSMYYNI-UHFFFAOYSA-N 1-[[7-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxy-3,4-dihydro-2h-chromen-2-yl]methyl]piperidine-4-carboxamide Chemical compound C1CC(C(=O)N)CCN1CC1OC2=CC(OC=3N=CC(=CC=3)C=3NN=CC=3)=CC=C2CC1 YHTSOUMTSMYYNI-UHFFFAOYSA-N 0.000 claims description 4
- LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 claims description 4
- KRARCKUKSJTPSB-UHFFFAOYSA-N 4-[1-[6-[4-(1h-pyrazol-5-yl)phenoxy]-1h-benzimidazol-2-yl]cyclopropyl]morpholine Chemical compound C1CC1(C=1NC2=CC=C(OC=3C=CC(=CC=3)C=3NN=CC=3)C=C2N=1)N1CCOCC1 KRARCKUKSJTPSB-UHFFFAOYSA-N 0.000 claims description 4
- GXWIGRSXMRTDEV-UHFFFAOYSA-N 4-[2-[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyquinolin-2-yl]oxyethyl]morpholine Chemical compound C=1C=C2C=C(OC=3N=CC(=CC=3)C=3NN=CC=3)C=CC2=NC=1OCCN1CCOCC1 GXWIGRSXMRTDEV-UHFFFAOYSA-N 0.000 claims description 4
- LUMQIBHJTJVLOE-UHFFFAOYSA-N 4-[2-[[6-[4-(1h-pyrazol-5-yl)phenoxy]-1,3-benzothiazol-2-yl]oxy]ethyl]morpholine Chemical compound N=1C2=CC=C(OC=3C=CC(=CC=3)C3=NNC=C3)C=C2SC=1OCCN1CCOCC1 LUMQIBHJTJVLOE-UHFFFAOYSA-N 0.000 claims description 4
- SVEZKSSEILSNRD-UHFFFAOYSA-N 4-[[6-[4-(1h-pyrazol-5-yl)phenoxy]pyrazolo[1,5-a]pyridin-2-yl]methyl]morpholine Chemical compound C1=C2C=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CN2N=C1CN1CCOCC1 SVEZKSSEILSNRD-UHFFFAOYSA-N 0.000 claims description 4
- DVQACHMDIVOPAK-UHFFFAOYSA-N 5-[4-(1h-pyrazol-5-yl)phenoxy]-1-(2-pyrrolidin-1-ylethyl)indazole Chemical compound C1CCCN1CCN(C1=CC=2)N=CC1=CC=2OC(C=C1)=CC=C1C1=CC=NN1 DVQACHMDIVOPAK-UHFFFAOYSA-N 0.000 claims description 4
- SHONPGQZLPCSSJ-UHFFFAOYSA-N 5-[6-[4-(1h-pyrazol-5-yl)phenoxy]imidazo[1,2-a]pyridin-2-yl]piperidin-2-one Chemical compound C1NC(=O)CCC1C1=CN(C=C(OC=2C=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 SHONPGQZLPCSSJ-UHFFFAOYSA-N 0.000 claims description 4
- GNCDLYBCTRJOJG-UHFFFAOYSA-N 6-[4-(1h-pyrazol-5-yl)phenoxy]-2-(pyrrolidin-1-ylmethyl)-1h-benzimidazole Chemical compound N=1C2=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC=C2NC=1CN1CCCC1 GNCDLYBCTRJOJG-UHFFFAOYSA-N 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 125000000532 dioxanyl group Chemical group 0.000 claims description 4
- JNTJGVDRAGDWOA-UHFFFAOYSA-N morpholin-4-yl-[7-[4-(1h-pyrazol-5-yl)phenoxy]imidazo[1,2-a]pyridin-2-yl]methanone Chemical compound C=1N2C=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC2=NC=1C(=O)N1CCOCC1 JNTJGVDRAGDWOA-UHFFFAOYSA-N 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- HVZVESFDQUAIOF-UHFFFAOYSA-N n,n-dimethyl-1-[6-[4-(1h-pyrazol-5-yl)phenoxy]-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound C=1C=C2OC(CN(C)C)CCC2=CC=1OC(C=C1)=CC=C1C1=CC=NN1 HVZVESFDQUAIOF-UHFFFAOYSA-N 0.000 claims description 4
- SFKGHUBIMIFHLO-UHFFFAOYSA-N n,n-dimethyl-1-[6-[4-(1h-pyrazol-5-yl)phenoxy]quinolin-2-yl]methanamine Chemical compound C1=CC2=NC(CN(C)C)=CC=C2C=C1OC(C=C1)=CC=C1C1=CC=NN1 SFKGHUBIMIFHLO-UHFFFAOYSA-N 0.000 claims description 4
- SCMWAUGVDKCBCH-UHFFFAOYSA-N n-ethyl-n-methyl-2-[5-[4-(1h-pyrazol-5-yl)phenoxy]indazol-2-yl]ethanamine Chemical compound C1=CC2=NN(CCN(C)CC)C=C2C=C1OC(C=C1)=CC=C1C1=CC=NN1 SCMWAUGVDKCBCH-UHFFFAOYSA-N 0.000 claims description 4
- CVSQXIMBBJFSPS-UHFFFAOYSA-N n-methyl-1-[[6-[4-(1h-pyrazol-5-yl)phenoxy]-2,3-dihydro-1-benzofuran-2-yl]methyl]piperidine-4-carboxamide Chemical compound C1CC(C(=O)NC)CCN1CC1OC2=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC=C2C1 CVSQXIMBBJFSPS-UHFFFAOYSA-N 0.000 claims description 4
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- 125000005960 1,4-diazepanyl group Chemical group 0.000 claims description 3
- 125000005962 1,4-oxazepanyl group Chemical group 0.000 claims description 3
- OCELLLYRRBLAMV-UHFFFAOYSA-N 1-[4-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxy-1-benzofuran-3-yl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=COC2=CC(OC=3N=CC(=CC=3)C=3NN=CC=3)=CC=C12 OCELLLYRRBLAMV-UHFFFAOYSA-N 0.000 claims description 3
- UCWQSHJAZYBADV-UHFFFAOYSA-N 1-[4-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyisoquinolin-3-yl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CC2=CC(OC=3N=CC(=CC=3)C=3NN=CC=3)=CC=C2C=N1 UCWQSHJAZYBADV-UHFFFAOYSA-N 0.000 claims description 3
- NUPLOPWLZHTNDF-UHFFFAOYSA-N 1-[4-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxynaphthalen-2-yl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CC=C(C=C(OC=2N=CC(=CC=2)C=2NN=CC=2)C=C2)C2=C1 NUPLOPWLZHTNDF-UHFFFAOYSA-N 0.000 claims description 3
- QQKHJJHHOZZJKY-UHFFFAOYSA-N 1-[4-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyquinolin-2-yl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CC=C(C=C(OC=2N=CC(=CC=2)C2=NNC=C2)C=C2)C2=N1 QQKHJJHHOZZJKY-UHFFFAOYSA-N 0.000 claims description 3
- CDRSYTCQSAZTAA-UHFFFAOYSA-N 2-(morpholin-4-ylmethyl)-6-[4-(1h-pyrazol-5-yl)phenoxy]-1,3-benzoxazole Chemical compound N=1C2=CC=C(OC=3C=CC(=CC=3)C=3NN=CC=3)C=C2OC=1CN1CCOCC1 CDRSYTCQSAZTAA-UHFFFAOYSA-N 0.000 claims description 3
- BKFFGRPXXSIZOW-UHFFFAOYSA-N 2-[(4-methylpiperidin-1-yl)methyl]-6-[4-(1h-pyrazol-5-yl)phenoxy]-1h-benzimidazole Chemical compound C1CC(C)CCN1CC1=NC2=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC=C2N1 BKFFGRPXXSIZOW-UHFFFAOYSA-N 0.000 claims description 3
- WYOJZQODEUATEL-UHFFFAOYSA-N 2-hydroxy-1-[4-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyquinolin-2-yl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)CO)CCN1CC1=CC=C(C=C(OC=2N=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 WYOJZQODEUATEL-UHFFFAOYSA-N 0.000 claims description 3
- IWYPAPIWVPHFQN-UHFFFAOYSA-N 2-methoxy-1-[4-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyquinolin-2-yl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)COC)CCN1CC1=CC=C(C=C(OC=2N=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 IWYPAPIWVPHFQN-UHFFFAOYSA-N 0.000 claims description 3
- KEIYSFUUQFYDLG-UHFFFAOYSA-N 5-(1h-pyrazol-5-yl)-2-[[2-(pyrrolidin-1-ylmethyl)-2,3-dihydro-1-benzofuran-6-yl]oxy]pyridine Chemical compound C1CCCN1CC(OC1=C2)CC1=CC=C2OC(N=C1)=CC=C1C1=CC=NN1 KEIYSFUUQFYDLG-UHFFFAOYSA-N 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000003725 azepanyl group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- MTDQKWPQAVNILY-UHFFFAOYSA-N n-ethyl-n-[[6-[4-(1h-pyrazol-5-yl)phenoxy]-1h-benzimidazol-2-yl]methyl]ethanamine Chemical compound C=1C=C2NC(CN(CC)CC)=NC2=CC=1OC(C=C1)=CC=C1C1=CC=NN1 MTDQKWPQAVNILY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- CBXSVYDQRXUHOZ-SFHVURJKSA-N (3s)-1-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyquinolin-2-yl]methyl]pyrrolidin-3-ol Chemical compound C1[C@@H](O)CCN1CC1=CC=C(C=C(OC=2N=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 CBXSVYDQRXUHOZ-SFHVURJKSA-N 0.000 claims description 2
- DDNDGMWWIBXYCG-SANMLTNESA-N (3s)-3-hydroxy-1-[1-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxynaphthalen-2-yl]methyl]piperidin-4-yl]pyrrolidin-2-one Chemical compound O=C1[C@@H](O)CCN1C1CCN(CC=2C=C3C=CC(OC=4N=CC(=CC=4)C=4NN=CC=4)=CC3=CC=2)CC1 DDNDGMWWIBXYCG-SANMLTNESA-N 0.000 claims description 2
- GTJLDVVTURSXGH-HNNXBMFYSA-N (3s)-3-methyl-4-[[6-[4-(1h-pyrazol-5-yl)phenoxy]-1h-benzimidazol-2-yl]methyl]morpholine Chemical compound C[C@H]1COCCN1CC1=NC2=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC=C2N1 GTJLDVVTURSXGH-HNNXBMFYSA-N 0.000 claims description 2
- AEKZLAYERXIEPV-HNNXBMFYSA-N (3s)-n-[[6-[4-(1h-pyrazol-5-yl)phenoxy]-1h-benzimidazol-2-yl]methyl]oxolan-3-amine Chemical compound N=1C2=CC(OC=3C=CC(=CC=3)C=3NN=CC=3)=CC=C2NC=1CN[C@H]1CCOC1 AEKZLAYERXIEPV-HNNXBMFYSA-N 0.000 claims description 2
- IFPGAJVLPUNQML-UHFFFAOYSA-N 1-[1-[[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxy-2,3-dihydro-1-benzofuran-2-yl]methyl]piperidin-4-yl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1CCN(CC2OC3=CC(OC=4N=CC(=CC=4)C=4NN=CC=4)=CC=C3C2)CC1 IFPGAJVLPUNQML-UHFFFAOYSA-N 0.000 claims description 2
- DODRESGUWBQESN-UHFFFAOYSA-N 1-[4-[2-[5-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyindazol-1-yl]ethyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CCN1C2=CC=C(OC=3N=CC(=CC=3)C=3NN=CC=3)C=C2C=N1 DODRESGUWBQESN-UHFFFAOYSA-N 0.000 claims description 2
- RCTXHOZAIVHGFY-UHFFFAOYSA-N 1-[4-[2-[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxy-1-benzofuran-3-yl]ethyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CCC1=COC2=CC(OC=3N=CC(=CC=3)C=3NN=CC=3)=CC=C12 RCTXHOZAIVHGFY-UHFFFAOYSA-N 0.000 claims description 2
- AKQQLRQDMZSMFD-UHFFFAOYSA-N 1-[4-[2-[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxy-2,3-dihydro-1-benzofuran-3-yl]ethyl]-1,4-diazepan-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCCN1CCC1C2=CC=C(OC=3N=CC(=CC=3)C=3NN=CC=3)C=C2OC1 AKQQLRQDMZSMFD-UHFFFAOYSA-N 0.000 claims description 2
- DWNTUXDWDNLLIM-UHFFFAOYSA-N 1-[4-[6-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxyquinolin-2-yl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C1=CC=C(C=C(OC=2N=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 DWNTUXDWDNLLIM-UHFFFAOYSA-N 0.000 claims description 2
- IZCIVWZHDWJIBQ-UHFFFAOYSA-N 1-[4-[[5-[5-(1h-pyrazol-5-yl)pyridin-2-yl]oxy-1h-indol-2-yl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CC2=CC(OC=3N=CC(=CC=3)C=3NN=CC=3)=CC=C2N1 IZCIVWZHDWJIBQ-UHFFFAOYSA-N 0.000 claims description 2
- UJZIDMOAVRUZRG-UHFFFAOYSA-N 1-[4-[[6-[4-(1h-pyrazol-5-yl)phenoxy]quinolin-2-yl]methyl]piperazin-1-yl]propan-1-one Chemical compound C1CN(C(=O)CC)CCN1CC1=CC=C(C=C(OC=2C=CC(=CC=2)C=2NN=CC=2)C=C2)C2=N1 UJZIDMOAVRUZRG-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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| US201261672504P | 2012-07-17 | 2012-07-17 | |
| US61/672,504 | 2012-07-17 | ||
| PCT/US2013/050624 WO2014014874A1 (en) | 2012-07-17 | 2013-07-16 | Pyrazole derivatives which inhibit leukotriene production |
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| JP2015523387A5 JP2015523387A5 (enExample) | 2016-09-01 |
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| JP (1) | JP6256467B2 (enExample) |
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| TW (1) | TW201416354A (enExample) |
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| JP2016523982A (ja) * | 2013-07-15 | 2016-08-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ロイコトリエン生成の阻害剤 |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8551982B2 (en) | 2011-03-14 | 2013-10-08 | Boehringer Ingelheim International Gmbh | Benzodioxane inhibitors of leukotriene production |
| EP2734516B1 (en) | 2011-07-19 | 2015-06-17 | Boehringer Ingelheim International GmbH | Arylpyrazole ethers as inhibitors of leukotriene a4 hydrolase |
| EP2822942B1 (en) | 2012-03-06 | 2017-05-10 | Boehringer Ingelheim International GmbH | Benzodioxanes for inhibiting leukotriene production |
| JP6080226B2 (ja) | 2012-03-06 | 2017-02-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 他の活性物質と組み合わせたロイコトリエン産生阻害用ベンゾジオキサン |
| EP2885285B1 (en) | 2012-07-17 | 2016-10-19 | Boehringer Ingelheim International GmbH | Pyrazole drivatives which inhibit leukotriene production |
| JP6353899B2 (ja) * | 2013-07-15 | 2018-07-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ロイコトリエン生成の阻害剤 |
| MX2016008247A (es) | 2013-12-20 | 2016-10-21 | Novartis Ag | Derivados de acido heteroaril butanoico como inhibidores de lta4h. |
| JP6337124B2 (ja) * | 2013-12-23 | 2018-06-06 | パーデュー、ファーマ、リミテッド、パートナーシップ | インダゾール及びその使用 |
| ES2789756T3 (es) | 2015-12-23 | 2020-10-26 | Merck Sharp & Dohme | Moduladores alostéricos de 6,7-dihidro-5H-pirrolo[3,4-b]piridin-5-ona del receptor de acetilcolina muscarínico M4 |
| MX2019003136A (es) | 2016-09-19 | 2019-07-18 | Bayer Cropscience Ag | Derivados de pirazolo [1,5-a]piridina y su uso como pesticidas. |
| WO2019111218A1 (en) | 2017-12-08 | 2019-06-13 | Cadila Healthcare Limited | Novel heterocyclic compounds as irak4 inhibitors |
| WO2019149522A1 (en) * | 2018-01-31 | 2019-08-08 | Merck Patent Gmbh | Quinoline compounds as irak inhibitors and uses thereof |
| ES2906077T3 (es) | 2018-02-21 | 2022-04-13 | Bayer Ag | Derivados de heterociclos bicíclicos condensados como pesticidas |
| ES2929476T3 (es) | 2018-03-12 | 2022-11-29 | Bayer Ag | Derivados heterocíclicos bicíclicos condensados como plaguicidas |
| MX2021002949A (es) | 2018-09-13 | 2021-05-12 | Bayer Ag | Derivados heterociclicos como plaguicidas. |
| WO2020097398A1 (en) | 2018-11-07 | 2020-05-14 | Dana-Farber Cancer Institute, Inc. | Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof |
| CN110229091B (zh) * | 2019-06-21 | 2022-11-22 | 天津科技大学 | 具有白三烯a4水解酶抑制作用的1,5-二取代吲哚衍生物及应用 |
| PH12022551379A1 (en) | 2019-12-06 | 2023-05-03 | Vertex Pharma | Substituted tetrahydrofurans as modulators of sodium channels |
| CN113045551B (zh) * | 2019-12-27 | 2024-07-09 | 广东东阳光药业股份有限公司 | 一种作为甲状腺激素β受体激动剂的化合物及其用途 |
| CA3181537A1 (en) | 2020-05-06 | 2021-11-11 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors |
| KR20230051227A (ko) | 2020-08-14 | 2023-04-17 | 노파르티스 아게 | 헤테로아릴 치환된 스피로피페리디닐 유도체 및 이의 제약 용도 |
| WO2022140527A1 (en) | 2020-12-23 | 2022-06-30 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors |
| DK4347031T3 (da) | 2021-06-04 | 2025-12-01 | Vertex Pharma | N-(hydroxyalkyl-(hetero)aryl)-tetrahydrofuran-carboxamider som modulatorer af natriumkanaler |
| AU2022376563A1 (en) | 2021-11-01 | 2023-12-07 | Alkahest, Inc. | Benzodioxane modulators of leukotriene a4 hydrolase (lta4h) for prevention and treatment of aging-associated diseases |
| CA3234638A1 (en) | 2021-11-09 | 2023-05-19 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors |
| TW202325289A (zh) | 2021-11-09 | 2023-07-01 | 美商雅捷可斯治療公司 | Jak2抑制劑之形式及組合物 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4918092A (en) | 1983-12-21 | 1990-04-17 | Merck Frosst Canada, Inc. | Leukotriene antagonists |
| US5120758A (en) | 1991-02-08 | 1992-06-09 | Ciba-Geigy Corporation | Certain benzodioxole, benzodioxane and benzodioxepin derivatives useful as 5-lipoxygenase inhibitors |
| DE4127849A1 (de) | 1991-08-22 | 1993-02-25 | Merck Patent Gmbh | Benzodioxanderivate |
| US5585492A (en) | 1994-10-11 | 1996-12-17 | G. D. Searle & Co. | LTA4 Hydrolase inhibitors |
| US6506876B1 (en) | 1994-10-11 | 2003-01-14 | G.D. Searle & Co. | LTA4 hydrolase inhibitor pharmaceutical compositions and methods of use |
| DE19705450A1 (de) | 1997-02-13 | 1998-08-20 | Merck Patent Gmbh | Bicyclische aromatische Aminosäuren |
| DE19821003A1 (de) | 1998-05-11 | 1999-11-18 | Dresden Arzneimittel | Neue 1,2,5-trisubstituierte 1,2-dihydro-indazol-3-one mit antiasthmatischer, antiallergischer, entzündungshemmender, immunmodulierender und neuroprotektiver Wirkung, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| PL362919A1 (en) | 2000-10-26 | 2004-11-02 | Pfizer Products Inc. | Pyrimidine-2,4,6-trione metalloproteinase inhibitors |
| US20060019269A1 (en) | 2002-10-17 | 2006-01-26 | Decode Genetics, Inc. | Susceptibility gene for myocardial infarction, stroke, and PAOD, methods of treatment |
| ATE441417T1 (de) * | 2002-12-20 | 2009-09-15 | Glaxo Group Ltd | Benzoädüazepinderivate für die behandlung von neurologischen krankheiten |
| US7098222B2 (en) | 2004-05-12 | 2006-08-29 | Abbott Laboratories | Bicyclic-substituted amines having cyclic-substituted monocyclic substituents |
| BRPI0518508A2 (pt) | 2005-01-07 | 2008-11-25 | Pfizer Prod Inc | compostos de quinolina heteroaromÁticos e seu uso como inibidores de pde10 |
| KR20080003385A (ko) | 2005-03-31 | 2008-01-07 | 얀센 파마슈티카 엔.브이. | 페닐 및 피리딜 lta4h 조절제 |
| JP5133889B2 (ja) | 2005-09-21 | 2013-01-30 | デコード ジェネティクス イーエイチエフ | 炎症治療のためのビアリール基置換複素環lta4h阻害剤 |
| AU2006327243A1 (en) | 2005-12-21 | 2007-06-28 | Decode Genetics Ehf | N-linked aryl heteroaryl inhibitors of LTA4H for treating inflammation |
| US7750012B2 (en) | 2005-12-21 | 2010-07-06 | Decode Genetics Ehf | Biaryl nitrogen-heterocycle inhibitors of LTA4H for treating inflammation |
| CL2007003065A1 (es) | 2006-10-24 | 2008-01-25 | Wyeth Corp | Compuestos derivados de benzodioxano, agonista 5ht2c, composicion farmaceutica que lois comprende; y sus uso en el tratamiento de un trastorno psicotico, ansiedad, depresion, trastorno bipolar, sindrome premenstrual, entre otros |
| DK2139881T3 (da) * | 2007-04-04 | 2012-01-30 | Pulmagen Therapeutics Asthma Ltd | Quinoliner og deres terapeutiske anvendelse |
| JP2011512359A (ja) * | 2008-02-14 | 2011-04-21 | アミラ ファーマシューティカルズ,インク. | プロスタグランジンd2受容体のアンタゴニストとしての環式ジアリールエーテル化合物 |
| RS52712B (sr) | 2008-04-11 | 2013-08-30 | Janssen Pharmaceutica N.V. | Tiazolopiridin-2-iloksi-fenil i tiazolopirazin-2-iloksi-fenil amini kao modulatori leukotrien a4 hidrolaze |
| WO2011032050A2 (en) | 2009-09-11 | 2011-03-17 | Trius Therapeutics, Inc. | Gyrase inhibitors |
| JP5856064B2 (ja) * | 2009-11-17 | 2016-02-09 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 治療特性を有する1,4−ベンゾジアゼピン−2,5−ジオンおよび関連化合物 |
| CN102946877B (zh) | 2010-03-18 | 2019-07-05 | 香港科技大学 | 乳突果及其分离的化合物在制备用于治疗神经疾病的药物中的用途 |
| US8551982B2 (en) | 2011-03-14 | 2013-10-08 | Boehringer Ingelheim International Gmbh | Benzodioxane inhibitors of leukotriene production |
| EP2734516B1 (en) * | 2011-07-19 | 2015-06-17 | Boehringer Ingelheim International GmbH | Arylpyrazole ethers as inhibitors of leukotriene a4 hydrolase |
| EP2822942B1 (en) | 2012-03-06 | 2017-05-10 | Boehringer Ingelheim International GmbH | Benzodioxanes for inhibiting leukotriene production |
| JP6080226B2 (ja) | 2012-03-06 | 2017-02-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 他の活性物質と組み合わせたロイコトリエン産生阻害用ベンゾジオキサン |
| EP2885285B1 (en) | 2012-07-17 | 2016-10-19 | Boehringer Ingelheim International GmbH | Pyrazole drivatives which inhibit leukotriene production |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016523982A (ja) * | 2013-07-15 | 2016-08-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ロイコトリエン生成の阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2885285B1 (en) | 2016-10-19 |
| JP2015523387A (ja) | 2015-08-13 |
| US20140031339A1 (en) | 2014-01-30 |
| US9403830B2 (en) | 2016-08-02 |
| AR091786A1 (es) | 2015-02-25 |
| WO2014014874A1 (en) | 2014-01-23 |
| TW201416354A (zh) | 2014-05-01 |
| EP2885285A1 (en) | 2015-06-24 |
| UY34917A (es) | 2014-01-31 |
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