ES2561210T3 - Derivados de piridina pirazolo como inhibidores de la NADPH oxidasa - Google Patents
Derivados de piridina pirazolo como inhibidores de la NADPH oxidasa Download PDFInfo
- Publication number
- ES2561210T3 ES2561210T3 ES09815761.3T ES09815761T ES2561210T3 ES 2561210 T3 ES2561210 T3 ES 2561210T3 ES 09815761 T ES09815761 T ES 09815761T ES 2561210 T3 ES2561210 T3 ES 2561210T3
- Authority
- ES
- Spain
- Prior art keywords
- optionally substituted
- pyrazolo
- pyridine
- alkyl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 108010002998 NADPH Oxidases Proteins 0.000 title claims description 38
- 102000004722 NADPH Oxidases Human genes 0.000 title claims description 38
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title description 5
- 239000003112 inhibitor Substances 0.000 title description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title description 3
- -1 cyano, hydroxy, mercapto Chemical class 0.000 claims abstract description 247
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 112
- UCBCBMOOIZMOTR-UHFFFAOYSA-N pyrazine;pyridine Chemical class C1=CC=NC=C1.C1=CN=CC=N1 UCBCBMOOIZMOTR-UHFFFAOYSA-N 0.000 claims abstract description 60
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 57
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 53
- 125000005017 substituted alkenyl group Chemical group 0.000 claims abstract description 47
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 41
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 38
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 35
- 125000003118 aryl group Chemical group 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 18
- 125000002252 acyl group Chemical group 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 16
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 14
- 125000004426 substituted alkynyl group Chemical group 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 9
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 7
- 125000005415 substituted alkoxy group Chemical group 0.000 claims abstract description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims abstract description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 5
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 5
- 125000001424 substituent group Chemical group 0.000 claims abstract description 5
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims abstract description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 112
- 201000010099 disease Diseases 0.000 claims description 57
- 208000035475 disorder Diseases 0.000 claims description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
- 206010028980 Neoplasm Diseases 0.000 claims description 50
- 230000033115 angiogenesis Effects 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 27
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 22
- 208000023504 respiratory system disease Diseases 0.000 claims description 21
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 20
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 19
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 18
- 208000027866 inflammatory disease Diseases 0.000 claims description 16
- 208000017169 kidney disease Diseases 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 230000001419 dependent effect Effects 0.000 claims description 14
- ICZVBOAABXHPSZ-UHFFFAOYSA-N piperidine-2,5-dione Chemical compound O=C1CCC(=O)NC1 ICZVBOAABXHPSZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 208000020084 Bone disease Diseases 0.000 claims description 12
- 208000002193 Pain Diseases 0.000 claims description 12
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 12
- 230000036407 pain Effects 0.000 claims description 12
- 230000008733 trauma Effects 0.000 claims description 12
- 208000010668 atopic eczema Diseases 0.000 claims description 11
- 230000001850 reproductive effect Effects 0.000 claims description 11
- 230000000172 allergic effect Effects 0.000 claims description 10
- 210000003027 ear inner Anatomy 0.000 claims description 10
- 230000002008 hemorrhagic effect Effects 0.000 claims description 10
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 9
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 9
- 206010040070 Septic Shock Diseases 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 208000030159 metabolic disease Diseases 0.000 claims description 9
- OUZMVFUWRAVKJL-UHFFFAOYSA-N 2-benzyl-4-[(3-methoxyphenyl)methyl]-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound COC1=CC=CC(CC2=C3C(=O)N(CC=4C=CC=CC=4)NC3=CC(=O)N2CC=2N=CC=CC=2)=C1 OUZMVFUWRAVKJL-UHFFFAOYSA-N 0.000 claims description 8
- 208000032456 Hemorrhagic Shock Diseases 0.000 claims description 8
- 206010049771 Shock haemorrhagic Diseases 0.000 claims description 8
- 210000005095 gastrointestinal system Anatomy 0.000 claims description 8
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 7
- 206010002199 Anaphylactic shock Diseases 0.000 claims description 7
- 101000968308 Homo sapiens Dual oxidase 1 Proteins 0.000 claims description 7
- 101000968305 Homo sapiens Dual oxidase 2 Proteins 0.000 claims description 7
- 208000003455 anaphylaxis Diseases 0.000 claims description 7
- 208000019423 liver disease Diseases 0.000 claims description 7
- DUNOKHOOSPBBFW-UHFFFAOYSA-N 2,4-dimethyl-5-(2-morpholin-4-ylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(C)C(=O)C2=C(C)N1CCN1CCOCC1 DUNOKHOOSPBBFW-UHFFFAOYSA-N 0.000 claims description 6
- YBUKFWRURFMXJW-UHFFFAOYSA-N 2,4-dimethyl-5-(2-pyridin-2-ylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(C)C(=O)C2=C(C)N1CCC1=CC=CC=N1 YBUKFWRURFMXJW-UHFFFAOYSA-N 0.000 claims description 6
- ZXJKQNLCANIJDO-UHFFFAOYSA-N 2-benzyl-4-butyl-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(CC=3C=CC=CC=3)C(=O)C2=C(CCCC)N1CC1=CC=CC=N1 ZXJKQNLCANIJDO-UHFFFAOYSA-N 0.000 claims description 6
- HMZLMRLQFJOPSA-UHFFFAOYSA-N 4-butyl-2-methyl-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(C)C(=O)C2=C(CCCC)N1CC1=CC=CC=N1 HMZLMRLQFJOPSA-UHFFFAOYSA-N 0.000 claims description 6
- OPLWNUKRRKIZRG-UHFFFAOYSA-N 4-butyl-5-[(4-chlorophenyl)methyl]-2-methyl-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(C)C(=O)C2=C(CCCC)N1CC1=CC=C(Cl)C=C1 OPLWNUKRRKIZRG-UHFFFAOYSA-N 0.000 claims description 6
- OGWXPINUWDIXBE-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2,4-dimethyl-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(C)C(=O)C2=C(C)N1CC1=CC=C(Cl)C=C1 OGWXPINUWDIXBE-UHFFFAOYSA-N 0.000 claims description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 230000002314 neuroinflammatory effect Effects 0.000 claims description 6
- UQFLQCVYJWHATB-UHFFFAOYSA-N 2-cyclohexyl-4-methyl-5-[[2-(morpholin-4-ylmethyl)phenyl]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(C3CCCCC3)C(=O)C2=C(C)N1CC1=CC=CC=C1CN1CCOCC1 UQFLQCVYJWHATB-UHFFFAOYSA-N 0.000 claims description 5
- IODRHPFWTINVAF-UHFFFAOYSA-N 5-(furan-2-ylmethyl)-2,4-dimethyl-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(C)C(=O)C2=C(C)N1CC1=CC=CO1 IODRHPFWTINVAF-UHFFFAOYSA-N 0.000 claims description 5
- 206010044541 Traumatic shock Diseases 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- GWDCECQGWTWLNM-UHFFFAOYSA-N 2-benzyl-4-methyl-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(CC=3C=CC=CC=3)C(=O)C2=C(C)N1CC1=CC=CC=N1 GWDCECQGWTWLNM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 4
- RYXBDCGRGBJKOR-UHFFFAOYSA-N 5-(2-methoxyethyl)-4-methyl-2-(2-phenylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=1C(=O)N(CCOC)C(C)=C(C2=O)C=1NN2CCC1=CC=CC=C1 RYXBDCGRGBJKOR-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000006823 (C1-C6) acyl group Chemical group 0.000 claims description 3
- RQTCIHJTYXSNAH-UHFFFAOYSA-N 2,5-bis(2-methoxyethyl)-4-(3-phenoxypropyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=12C(=O)N(CCOC)NC2=CC(=O)N(CCOC)C=1CCCOC1=CC=CC=C1 RQTCIHJTYXSNAH-UHFFFAOYSA-N 0.000 claims description 3
- FKAKWDOGKQHZKQ-UHFFFAOYSA-N 2-(2-methoxyethyl)-4-methyl-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound CC1=C2C(=O)N(CCOC)NC2=CC(=O)N1CC1=CC=CC=N1 FKAKWDOGKQHZKQ-UHFFFAOYSA-N 0.000 claims description 3
- MSRMAMINSJYYAL-UHFFFAOYSA-N 2-[(2,5-dichlorophenyl)methyl]-4-methyl-5-(2-morpholin-4-ylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(CC=3C(=CC=C(Cl)C=3)Cl)C(=O)C2=C(C)N1CCN1CCOCC1 MSRMAMINSJYYAL-UHFFFAOYSA-N 0.000 claims description 3
- OIVBQOLEYJUBFJ-UHFFFAOYSA-N 2-[(2-chloro-4-fluorophenyl)methyl]-4-methyl-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(CC=3C(=CC(F)=CC=3)Cl)C(=O)C2=C(C)N1CC1=CC=CC=N1 OIVBQOLEYJUBFJ-UHFFFAOYSA-N 0.000 claims description 3
- GYZYSAGRZKIZMW-UHFFFAOYSA-N 2-[(4-chlorophenyl)methyl]-4-methyl-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(CC=3C=CC(Cl)=CC=3)C(=O)C2=C(C)N1CC1=CC=CC=N1 GYZYSAGRZKIZMW-UHFFFAOYSA-N 0.000 claims description 3
- DKGSXHQOYLMYAX-UHFFFAOYSA-N 2-[2-(4-chlorophenoxy)ethyl]-4-methyl-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(CCOC=3C=CC(Cl)=CC=3)C(=O)C2=C(C)N1CC1=CC=CC=N1 DKGSXHQOYLMYAX-UHFFFAOYSA-N 0.000 claims description 3
- DJKCKEORYZBAFA-UHFFFAOYSA-N 2-benzyl-4-(3-chlorophenyl)-5-(2-methoxyethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound N1N(CC=2C=CC=CC=2)C(=O)C=2C1=CC(=O)N(CCOC)C=2C1=CC=CC(Cl)=C1 DJKCKEORYZBAFA-UHFFFAOYSA-N 0.000 claims description 3
- PYVNRQQEFLVCIB-UHFFFAOYSA-N 2-benzyl-4-butyl-5-[(3,5-dimethoxyphenyl)methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(CC=3C=CC=CC=3)C(=O)C2=C(CCCC)N1CC1=CC(OC)=CC(OC)=C1 PYVNRQQEFLVCIB-UHFFFAOYSA-N 0.000 claims description 3
- CIBZFHVFWWSWSA-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-2-(2-methoxyethyl)-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=1C=C(Cl)C(Cl)=CC=1C1=C2C(=O)N(CCOC)NC2=CC(=O)N1CC1=CC=CC=N1 CIBZFHVFWWSWSA-UHFFFAOYSA-N 0.000 claims description 3
- JBQGZHNQAXPDMO-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-5-(2-methoxyethyl)-2-methyl-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound N1N(C)C(=O)C=2C1=CC(=O)N(CCOC)C=2C1=CC=C(Cl)C(Cl)=C1 JBQGZHNQAXPDMO-UHFFFAOYSA-N 0.000 claims description 3
- AIWGTKUMEQJPNL-UHFFFAOYSA-N 4-(3,5-dichlorophenyl)-5-(2-methoxyethyl)-2-methyl-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound N1N(C)C(=O)C=2C1=CC(=O)N(CCOC)C=2C1=CC(Cl)=CC(Cl)=C1 AIWGTKUMEQJPNL-UHFFFAOYSA-N 0.000 claims description 3
- XRENEWWCQFFACG-UHFFFAOYSA-N 4-(3-chlorophenyl)-5-(2-morpholin-4-ylethyl)-2-(2-phenylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound ClC1=CC=CC(C2=C3C(=O)N(CCC=4C=CC=CC=4)NC3=CC(=O)N2CCN2CCOCC2)=C1 XRENEWWCQFFACG-UHFFFAOYSA-N 0.000 claims description 3
- PJMZQAMXNBLGCM-UHFFFAOYSA-N 4-(4-chlorophenyl)-2,5-bis(2-methoxyethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=12C(=O)N(CCOC)NC2=CC(=O)N(CCOC)C=1C1=CC=C(Cl)C=C1 PJMZQAMXNBLGCM-UHFFFAOYSA-N 0.000 claims description 3
- ZLIGEFJQLFGMSA-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(2-methoxyethyl)-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=1C=C(Cl)C=CC=1C1=C2C(=O)N(CCOC)NC2=CC(=O)N1CC1=CC=CC=N1 ZLIGEFJQLFGMSA-UHFFFAOYSA-N 0.000 claims description 3
- CORJTERQSHBEDP-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(2-methoxyethyl)-5-[(3-methoxyphenyl)methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=1C=C(Cl)C=CC=1C1=C2C(=O)N(CCOC)NC2=CC(=O)N1CC1=CC=CC(OC)=C1 CORJTERQSHBEDP-UHFFFAOYSA-N 0.000 claims description 3
- RRFAQVAZVANUEH-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-methyl-5-[(5-oxopyrrolidin-3-yl)methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=1C=C(Cl)C=CC=1C1=C2C(=O)N(C)NC2=CC(=O)N1CC1CNC(=O)C1 RRFAQVAZVANUEH-UHFFFAOYSA-N 0.000 claims description 3
- AGDUCJQYJICGEM-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-(2-methoxyethyl)-2-methyl-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound N1N(C)C(=O)C=2C1=CC(=O)N(CCOC)C=2C1=CC=C(Cl)C=C1 AGDUCJQYJICGEM-UHFFFAOYSA-N 0.000 claims description 3
- MJYGRDRUXPRNTI-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-(2-morpholin-4-ylethyl)-2-(2-phenylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CC(Cl)=CC=C1C1=C2C(=O)N(CCC=3C=CC=CC=3)NC2=CC(=O)N1CCN1CCOCC1 MJYGRDRUXPRNTI-UHFFFAOYSA-N 0.000 claims description 3
- PBXXLIYKNZZAQX-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-[(4-chlorophenyl)methyl]-2-(2-methoxyethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=1C=C(Cl)C=CC=1C1=C2C(=O)N(CCOC)NC2=CC(=O)N1CC1=CC=C(Cl)C=C1 PBXXLIYKNZZAQX-UHFFFAOYSA-N 0.000 claims description 3
- SVIUNYOULJGPQL-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-[(4-methoxyphenyl)methyl]-2-(2-morpholin-4-ylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C=C(NN(CCN2CCOCC2)C2=O)C2=C1C1=CC=C(Cl)C=C1 SVIUNYOULJGPQL-UHFFFAOYSA-N 0.000 claims description 3
- RDLGXRPESIUATF-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-methyl-2-(1-methylpiperidin-4-yl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1CN(C)CCC1N1C(=O)C2=C(C=3C=CC(Cl)=CC=3)N(C)C(=O)C=C2N1 RDLGXRPESIUATF-UHFFFAOYSA-N 0.000 claims description 3
- OVUSAYDQNMMGQW-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-methyl-2-(2-morpholin-4-ylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound N1N(CCN2CCOCC2)C(=O)C=2C1=CC(=O)N(C)C=2C1=CC=C(Cl)C=C1 OVUSAYDQNMMGQW-UHFFFAOYSA-N 0.000 claims description 3
- QXDWRQQGYPMLHN-UHFFFAOYSA-N 4-[(4-fluorophenoxy)methyl]-2-(2-methoxyethyl)-5-[(3-methoxyphenyl)methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C=1C=C(F)C=CC=1OCC1=C2C(=O)N(CCOC)NC2=CC(=O)N1CC1=CC=CC(OC)=C1 QXDWRQQGYPMLHN-UHFFFAOYSA-N 0.000 claims description 3
- YXCJVHIMJFZHRX-UHFFFAOYSA-N 4-[(4-fluorophenoxy)methyl]-5-methyl-2-(2-morpholin-4-ylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound N1N(CCN2CCOCC2)C(=O)C=2C1=CC(=O)N(C)C=2COC1=CC=C(F)C=C1 YXCJVHIMJFZHRX-UHFFFAOYSA-N 0.000 claims description 3
- FRANYBFLIHSLKR-UHFFFAOYSA-N 4-methyl-2-(2-methylpropyl)-5-(2-morpholin-4-ylethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound CC1=C2C(=O)N(CC(C)C)NC2=CC(=O)N1CCN1CCOCC1 FRANYBFLIHSLKR-UHFFFAOYSA-N 0.000 claims description 3
- IDMMWOMTIJWNPH-UHFFFAOYSA-N 4-methyl-2-(2-phenylethyl)-5-(pyridin-2-ylmethyl)-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound O=C1C=C2NN(CCC=3C=CC=CC=3)C(=O)C2=C(C)N1CC1=CC=CC=N1 IDMMWOMTIJWNPH-UHFFFAOYSA-N 0.000 claims description 3
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| PCT/IB2009/054155 WO2010035220A1 (en) | 2008-09-23 | 2009-09-22 | Pyrazolo pyridine derivatives as nadph oxidase inhibitors |
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| EP2002835A1 (en) | 2007-06-04 | 2008-12-17 | GenKyo Tex | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2000176A1 (en) * | 2007-06-04 | 2008-12-10 | GenKyo Tex | Tetrahydroindole derivatives as NADPH Oxidase inhibitors |
| EP2165707A1 (en) | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2166010A1 (en) | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2166008A1 (en) | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2305679A1 (en) | 2009-09-28 | 2011-04-06 | GenKyoTex SA | Pyrazoline dione derivatives as nadph oxidase inhibitors |
| EP2361911A1 (en) | 2010-02-18 | 2011-08-31 | GenKyoTex SA | Pyrazolo piperidine derivatives as NADPH oxidase inhibitors |
| IN2015DN03761A (enExample) | 2012-10-24 | 2015-10-02 | Glucox Biotech Ab | |
| US20140212891A1 (en) * | 2013-01-29 | 2014-07-31 | Amina El Jamali | Compositions and Methods Using NOX5 |
| EP3258937A4 (en) | 2015-02-16 | 2018-10-31 | Glucox Biotech AB | N2-(3,4-dimethylphenyl)-6-((4-(p-tolyl)piperazin-1-yl)methyl)-1,3,5-triazine-2,4-diamine |
| CA3045944A1 (en) | 2016-12-07 | 2018-06-14 | Progenity, Inc. | Gastrointestinal tract detection methods, devices and systems |
| BR112019023109A2 (pt) | 2017-05-04 | 2020-05-26 | Glenmark Pharmaceuticals S.A. | Composto, composição farmacêutica e método para tratar uma doença, distúrbio, síndrome ou afecção mediada por nadph oxidase em um indivíduo |
| EP3479843A1 (en) | 2017-11-01 | 2019-05-08 | GenKyoTex Suisse SA | Use of nox inhibitors for treatment of cancer |
| US12227565B2 (en) | 2018-06-20 | 2025-02-18 | Biora Therapeutics, Inc. | Method of formulating a pharmaceutical composition comprising administering an immune modulator to the small intestine |
| CN113348011B (zh) | 2018-11-19 | 2023-04-18 | 比奥拉治疗股份有限公司 | 用生物治疗剂治疗疾病的方法和装置 |
| CN121197633A (zh) | 2019-12-13 | 2025-12-26 | 比特比德科有限责任公司 | 用于将治疗剂递送至胃肠道的可摄取装置 |
| US11896719B2 (en) | 2022-01-24 | 2024-02-13 | Calliditas Therapeutics Ab | Pharmaceutical compositions |
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| US3391407A (en) * | 1966-08-15 | 1968-07-09 | William A. Waters | Helmet |
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| DE3728278A1 (de) | 1986-12-17 | 1988-06-23 | Bayer Ag | Herbizide und fungizide mittel auf basis von substituierten pyrazolin-5-on derivaten |
| DE19518082A1 (de) | 1995-05-17 | 1996-11-21 | Merck Patent Gmbh | 4(-Arylaminomethylen)-2,4-dihydropyrazol-3-one |
| US5763496A (en) | 1995-11-27 | 1998-06-09 | The Research Foundation Of State University Of New York | Prevention of atherosclerosis using NADPH oxidase inhibitors |
| TW432073B (en) | 1995-12-28 | 2001-05-01 | Pfizer | Pyrazolopyridine compounds |
| WO1998037068A1 (en) | 1997-02-21 | 1998-08-27 | Bristol-Myers Squibb Company | Benzoic acid derivatives and related compounds as antiarrhythmic agents |
| IL144468A0 (en) | 2000-07-27 | 2002-05-23 | Pfizer Prod Inc | Use of growth hormone secretagogues for improvement of functional health status |
| US7902179B2 (en) | 2001-04-26 | 2011-03-08 | Ajinomoto Co., Inc. | Heterocyclic compounds |
| EP1291017A3 (en) | 2001-09-10 | 2003-07-02 | Warner-Lambert Company | Use of statins to inhibit formation of osteoclasts |
| CA2483306A1 (en) * | 2002-04-23 | 2003-11-06 | Shionogi & Co., Ltd. | Pyrazolo[1,5-a]pyrimidine derivative and nad(p)h oxidase inhibitor containing the same |
| WO2004005267A2 (en) | 2002-07-03 | 2004-01-15 | Janssen Pharmaceutica, N.V. | Heteroaryl compounds useful in treating inflammatory disorders |
| CN1774243A (zh) | 2003-02-28 | 2006-05-17 | 霍华德弗洛里实验生理及医药学院 | 治疗组合物 |
| EP1616576A4 (en) | 2003-04-08 | 2010-02-10 | Mitsubishi Tanabe Pharma Corp | SPECIFIC NAD (P) H OXIDASE HEMMER |
| WO2005080378A1 (ja) | 2004-02-24 | 2005-09-01 | Mitsubishi Pharma Corporation | 縮合ピリダジン誘導体 |
| JP2007529496A (ja) * | 2004-03-19 | 2007-10-25 | ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー | 抗菌剤としてのイミダゾピリジン及びイミダゾピリミジン誘導体 |
| WO2006041874A2 (en) | 2004-10-04 | 2006-04-20 | Myriad Genetics, Inc. | Compounds for alzheimer's disease |
| FR2882654B1 (fr) | 2005-03-01 | 2007-04-27 | Servier Lab | Utilisation de derives de la diosmetine pour le traitement et la prevention des pathologies thrombotiques |
| US7759337B2 (en) | 2005-03-03 | 2010-07-20 | Amgen Inc. | Phthalazine compounds and methods of use |
| US20070014739A1 (en) | 2005-07-14 | 2007-01-18 | Eldridge Gary R | Compositions and methods for controlling biofilms and bacterial infections |
| DE102005048897A1 (de) | 2005-10-12 | 2007-04-19 | Sanofi-Aventis Deutschland Gmbh | Diacylindazol-derivate als Inhibitoren von Lipasen und Phospholipasen |
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| EP2002835A1 (en) * | 2007-06-04 | 2008-12-17 | GenKyo Tex | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2000176A1 (en) | 2007-06-04 | 2008-12-10 | GenKyo Tex | Tetrahydroindole derivatives as NADPH Oxidase inhibitors |
| WO2009072643A1 (en) | 2007-12-03 | 2009-06-11 | Takeda Pharmaceutical Company Limited | Nitrogen-containing heterocyclic compound and use thereof |
| US20090163452A1 (en) | 2007-12-20 | 2009-06-25 | Schwartz Janice B | Compositions and methods for lowering serum cholesterol |
| FR2929276B1 (fr) | 2008-04-01 | 2010-04-23 | Servier Lab | Nouveaux derives de diosmetine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| EP2165707A1 (en) * | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2166010A1 (en) | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2166008A1 (en) * | 2008-09-23 | 2010-03-24 | Genkyo Tex Sa | Pyrazolo pyridine derivatives as NADPH oxidase inhibitors |
| EP2305679A1 (en) | 2009-09-28 | 2011-04-06 | GenKyoTex SA | Pyrazoline dione derivatives as nadph oxidase inhibitors |
| WO2011085293A1 (en) | 2010-01-08 | 2011-07-14 | Beth Israel Deaconess Medical Center | Methods and compositions for the treatment of migraine headaches |
| EP2361912A1 (en) | 2010-02-18 | 2011-08-31 | GenKyoTex SA | Pyrazolo piperidine derivatives as NADPH oxidase inhibitors |
| EP2361911A1 (en) | 2010-02-18 | 2011-08-31 | GenKyoTex SA | Pyrazolo piperidine derivatives as NADPH oxidase inhibitors |
| CN102014373B (zh) | 2010-11-22 | 2015-04-01 | 中兴通讯股份有限公司 | 一种激活配置的方法及装置 |
| EP2591782A1 (en) | 2011-11-11 | 2013-05-15 | Johann Wolfgang Goethe-Universität | Nadph oxidase 4 inhibitors and use thereof |
-
2008
- 2008-09-23 EP EP20080164849 patent/EP2166009A1/en not_active Withdrawn
-
2009
- 2009-09-22 JP JP2011527465A patent/JP5750372B2/ja not_active Expired - Fee Related
- 2009-09-22 BR BRPI0919331A patent/BRPI0919331A2/pt not_active IP Right Cessation
- 2009-09-22 WO PCT/IB2009/054155 patent/WO2010035220A1/en not_active Ceased
- 2009-09-22 AU AU2009298007A patent/AU2009298007B2/en not_active Ceased
- 2009-09-22 KR KR1020117006133A patent/KR101716511B1/ko not_active Expired - Fee Related
- 2009-09-22 RU RU2011116232/04A patent/RU2548022C2/ru active
- 2009-09-22 CA CA2737538A patent/CA2737538C/en not_active Expired - Fee Related
- 2009-09-22 EP EP09815761.3A patent/EP2342203B1/en active Active
- 2009-09-22 ES ES09815761.3T patent/ES2561210T3/es active Active
- 2009-09-22 CN CN200980133736.3A patent/CN102137862B/zh not_active Expired - Fee Related
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2011
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2013
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Also Published As
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| EP2342203B1 (en) | 2015-11-04 |
| RU2011116232A (ru) | 2012-10-27 |
| KR20110060901A (ko) | 2011-06-08 |
| JP2012502980A (ja) | 2012-02-02 |
| JP5750372B2 (ja) | 2015-07-22 |
| HK1159092A1 (en) | 2012-07-27 |
| AU2009298007A1 (en) | 2010-04-01 |
| IL211891B (en) | 2018-01-31 |
| EP2342203A1 (en) | 2011-07-13 |
| US20130158027A1 (en) | 2013-06-20 |
| CN102137862B (zh) | 2014-07-02 |
| EP2166009A1 (en) | 2010-03-24 |
| RU2548022C2 (ru) | 2015-04-10 |
| US20110178082A1 (en) | 2011-07-21 |
| WO2010035220A1 (en) | 2010-04-01 |
| US8455486B2 (en) | 2013-06-04 |
| IL211891A0 (en) | 2011-06-30 |
| CN102137862A (zh) | 2011-07-27 |
| AU2009298007B2 (en) | 2014-02-06 |
| US9006238B2 (en) | 2015-04-14 |
| CA2737538C (en) | 2019-04-23 |
| KR101716511B1 (ko) | 2017-03-14 |
| BRPI0919331A2 (pt) | 2015-12-29 |
| CA2737538A1 (en) | 2010-04-01 |
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