JP2008503531A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2008503531A5 JP2008503531A5 JP2007517186A JP2007517186A JP2008503531A5 JP 2008503531 A5 JP2008503531 A5 JP 2008503531A5 JP 2007517186 A JP2007517186 A JP 2007517186A JP 2007517186 A JP2007517186 A JP 2007517186A JP 2008503531 A5 JP2008503531 A5 JP 2008503531A5
- Authority
- JP
- Japan
- Prior art keywords
- ethyl
- oxo
- dihydropyridazine
- ylamino
- carboxylic acid
- 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.)
- Pending
Links
- -1 hydroxy, hydroxycarbonyl Chemical group 0.000 claims description 84
- 150000001875 compounds Chemical class 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000004442 acylamino group Chemical group 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- AYQAYXANVWKXST-UHFFFAOYSA-N (3-oxo-1h-2-benzofuran-1-yl) 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound O1C(=O)C2=CC=CC=C2C1OC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 AYQAYXANVWKXST-UHFFFAOYSA-N 0.000 claims description 3
- JIPDQAIEXJPADH-UHFFFAOYSA-N 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 JIPDQAIEXJPADH-UHFFFAOYSA-N 0.000 claims description 3
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
- YRTLKHAPXWLXBG-UHFFFAOYSA-N butanoyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound O=C1N(CC)N=C(C=2C=CC=CC=2)C(C(=O)OCOC(=O)CCC)=C1NC1=CC=CN=C1 YRTLKHAPXWLXBG-UHFFFAOYSA-N 0.000 claims description 3
- SVINEOXRWZEKBM-UHFFFAOYSA-N cyclohexyloxycarbonyloxymethyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenylpyridazine-4-carboxylate Chemical compound C1CCCCC1OC(=O)OCOC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CC=C1 SVINEOXRWZEKBM-UHFFFAOYSA-N 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- OEPNIULYTJOPOW-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl) 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound CCOC(=O)COC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 OEPNIULYTJOPOW-UHFFFAOYSA-N 0.000 claims description 2
- KVXKNJUOGZSBHV-UHFFFAOYSA-N (2-oxo-2-phenylmethoxyethyl) 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)COC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 KVXKNJUOGZSBHV-UHFFFAOYSA-N 0.000 claims description 2
- RRVRXMWPEHHLJX-UHFFFAOYSA-N (2-oxo-2-phenylmethoxyethyl) 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)COC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 RRVRXMWPEHHLJX-UHFFFAOYSA-N 0.000 claims description 2
- RFSRFPWPEPMVPE-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 1-ethyl-3-(4-methylphenyl)-5-[(4-methylpyridin-3-yl)amino]-6-oxopyridazine-4-carboxylate Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=C(C)C=C1 RFSRFPWPEPMVPE-UHFFFAOYSA-N 0.000 claims description 2
- 241001024304 Mino Species 0.000 claims description 2
- SUJKVNMXHCHELC-UHFFFAOYSA-N methyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound COC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 SUJKVNMXHCHELC-UHFFFAOYSA-N 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 125000005647 linker group Chemical group 0.000 claims 4
- UTFVFEWESJDJPX-UHFFFAOYSA-N 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenylpyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CC=C1 UTFVFEWESJDJPX-UHFFFAOYSA-N 0.000 claims 3
- 125000003118 aryl group Chemical group 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 230000001575 pathological effect Effects 0.000 claims 3
- MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims 2
- 201000004681 Psoriasis Diseases 0.000 claims 2
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims 2
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims 2
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 208000006673 asthma Diseases 0.000 claims 2
- 201000008937 atopic dermatitis Diseases 0.000 claims 2
- KWZNFMMDBXUYEK-UHFFFAOYSA-N benzyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CS1 KWZNFMMDBXUYEK-UHFFFAOYSA-N 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000005764 inhibitory process Effects 0.000 claims 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- ZQOVMCITMFRZGF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl) 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CCOC(=O)COC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CS1 ZQOVMCITMFRZGF-UHFFFAOYSA-N 0.000 claims 1
- WBNSRYIMLAZTFJ-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl) 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound O=C1N(CC)N=C(C=2SC=CC=2)C(C(=O)OCC(=O)OCC)=C1NC1=CC=CN=C1 WBNSRYIMLAZTFJ-UHFFFAOYSA-N 0.000 claims 1
- UXMXAWPLMKACIA-UHFFFAOYSA-N (2-oxo-1,3-dioxolan-4-yl) 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound C1OC(=O)OC1OC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 UXMXAWPLMKACIA-UHFFFAOYSA-N 0.000 claims 1
- ZFGXZAPWVWUKAF-UHFFFAOYSA-N (2-oxo-2-phenylmethoxyethyl) 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)COC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CS1 ZFGXZAPWVWUKAF-UHFFFAOYSA-N 0.000 claims 1
- TYMDATUIPDWLGT-UHFFFAOYSA-N (2-oxo-2-phenylmethoxyethyl) 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)COC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CS1 TYMDATUIPDWLGT-UHFFFAOYSA-N 0.000 claims 1
- REUFIMAVCLSMMJ-UHFFFAOYSA-N (2-oxo-2-pyridin-4-ylethyl) 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound C=1C=NC=CC=1C(=O)COC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 REUFIMAVCLSMMJ-UHFFFAOYSA-N 0.000 claims 1
- MINSMCISGFLMIQ-UHFFFAOYSA-N (2-oxo-2-pyrrolidin-1-ylethyl) 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound C1CCCN1C(=O)COC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 MINSMCISGFLMIQ-UHFFFAOYSA-N 0.000 claims 1
- OQPZLRXILZSINC-UHFFFAOYSA-N (3-amino-3-oxopropyl) 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound NC(=O)CCOC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 OQPZLRXILZSINC-UHFFFAOYSA-N 0.000 claims 1
- DMJCJQSMRTUWOS-UHFFFAOYSA-N (3-fluorophenyl)methyl 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound C=1C=CC(F)=CC=1COC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 DMJCJQSMRTUWOS-UHFFFAOYSA-N 0.000 claims 1
- RHKDFZKGDRQCPC-UHFFFAOYSA-N (4-fluorophenyl)methyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-thiophen-3-ylpyridazine-4-carboxylate Chemical compound C=1C=C(F)C=CC=1COC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C=1C=CSC=1 RHKDFZKGDRQCPC-UHFFFAOYSA-N 0.000 claims 1
- SUILFGYRLGYPIC-UHFFFAOYSA-N (4-fluorophenyl)methyl 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-3-ylpyridazine-4-carboxylate Chemical compound C=1C=C(F)C=CC=1COC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C=1C=CSC=1 SUILFGYRLGYPIC-UHFFFAOYSA-N 0.000 claims 1
- IGXQOAOVRWRXTR-UHFFFAOYSA-N (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound O1C(=O)OC(C)=C1COC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 IGXQOAOVRWRXTR-UHFFFAOYSA-N 0.000 claims 1
- QCLGYOHTBTZSDN-UHFFFAOYSA-N (6-ethoxy-6-oxohexyl) 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-3-ylpyridazine-4-carboxylate Chemical compound O=C1N(CC)N=C(C2=CSC=C2)C(C(=O)OCCCCCC(=O)OCC)=C1NC1=CC=CN=C1 QCLGYOHTBTZSDN-UHFFFAOYSA-N 0.000 claims 1
- PJDZQOIYQQRWJD-UHFFFAOYSA-N 1-cyclohexyloxycarbonyloxyethyl 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-phenylpyridazine-4-carboxylate Chemical compound C1CCCCC1OC(=O)OC(C)OC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 PJDZQOIYQQRWJD-UHFFFAOYSA-N 0.000 claims 1
- YYRKGSDUHBQLOB-UHFFFAOYSA-N 1-cyclohexyloxycarbonyloxyethyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenylpyridazine-4-carboxylate Chemical compound C1CCCCC1OC(=O)OC(C)OC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CC=C1 YYRKGSDUHBQLOB-UHFFFAOYSA-N 0.000 claims 1
- PYPSOMQKFXTIJF-UHFFFAOYSA-N 1-ethoxycarbonyloxyethyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenylpyridazine-4-carboxylate Chemical compound O=C1N(CC)N=C(C=2C=CC=CC=2)C(C(=O)OC(C)OC(=O)OCC)=C1NC1=CN=CC=C1C PYPSOMQKFXTIJF-UHFFFAOYSA-N 0.000 claims 1
- ROFGSTUXSJJPOV-UHFFFAOYSA-N 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-phenylpyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 ROFGSTUXSJJPOV-UHFFFAOYSA-N 0.000 claims 1
- ZXOWDVZMXXEVLN-UHFFFAOYSA-N 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CS1 ZXOWDVZMXXEVLN-UHFFFAOYSA-N 0.000 claims 1
- SVKAVXBNAOBVJC-UHFFFAOYSA-N 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CS1 SVKAVXBNAOBVJC-UHFFFAOYSA-N 0.000 claims 1
- JCCXNKIMXIQXQL-UHFFFAOYSA-N 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 JCCXNKIMXIQXQL-UHFFFAOYSA-N 0.000 claims 1
- KWKJBUWSUGOXAM-UHFFFAOYSA-N 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-2-ylpyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CS1 KWKJBUWSUGOXAM-UHFFFAOYSA-N 0.000 claims 1
- GAFOQWRUIGNQDB-UHFFFAOYSA-N 1-propan-2-yloxycarbonyloxyethyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenylpyridazine-4-carboxylate Chemical compound CC(C)OC(=O)OC(C)OC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CC=C1 GAFOQWRUIGNQDB-UHFFFAOYSA-N 0.000 claims 1
- YYYKMPCEPVSSSB-UHFFFAOYSA-N 1-propan-2-yloxycarbonyloxyethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound CC(C)OC(=O)OC(C)OC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 YYYKMPCEPVSSSB-UHFFFAOYSA-N 0.000 claims 1
- IUEMBCDGEXTGIJ-UHFFFAOYSA-N 2,2-dimethylbutanoyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound CCC(C)(C)C(=O)OCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 IUEMBCDGEXTGIJ-UHFFFAOYSA-N 0.000 claims 1
- CYPGRSZMLAOGFL-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 1-ethyl-5-(isoquinolin-4-ylamino)-3-(4-methylphenyl)-6-oxopyridazine-4-carboxylate Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=C(C)C=C1 CYPGRSZMLAOGFL-UHFFFAOYSA-N 0.000 claims 1
- LJGLLNSENMUOQF-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-phenylpyridazine-4-carboxylate Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 LJGLLNSENMUOQF-UHFFFAOYSA-N 0.000 claims 1
- GMJJBMAYDTZOMV-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenylpyridazine-4-carboxylate Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CC=C1 GMJJBMAYDTZOMV-UHFFFAOYSA-N 0.000 claims 1
- SBDIUDUAUBGHNR-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 SBDIUDUAUBGHNR-UHFFFAOYSA-N 0.000 claims 1
- ZPFDNXFWHRBUIQ-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 ZPFDNXFWHRBUIQ-UHFFFAOYSA-N 0.000 claims 1
- DXMXLLYJNAFHGX-UHFFFAOYSA-N 2-(dimethylamino)ethyl 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound CN(C)CCOC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 DXMXLLYJNAFHGX-UHFFFAOYSA-N 0.000 claims 1
- UTNBEFDPUZDWLI-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(C)(C)OC(=O)NCCOC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CS1 UTNBEFDPUZDWLI-UHFFFAOYSA-N 0.000 claims 1
- NFXMSFXHAXKYNP-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound CC(C)(C)OC(=O)NCCOC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 NFXMSFXHAXKYNP-UHFFFAOYSA-N 0.000 claims 1
- SPWNPRPDIBHYGB-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(C)(C)OC(=O)NCCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CS1 SPWNPRPDIBHYGB-UHFFFAOYSA-N 0.000 claims 1
- VPVMFVPGIBKFFG-UHFFFAOYSA-N 2-acetyloxyethyl 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound CC(=O)OCCOC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 VPVMFVPGIBKFFG-UHFFFAOYSA-N 0.000 claims 1
- QYNIQKVOSKJEDI-UHFFFAOYSA-N 2-acetyloxyethyl 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(=O)OCCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CS1 QYNIQKVOSKJEDI-UHFFFAOYSA-N 0.000 claims 1
- FIJLDENFNWSRBL-UHFFFAOYSA-N 2-methylpropanoyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound CC(C)C(=O)OCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 FIJLDENFNWSRBL-UHFFFAOYSA-N 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims 1
- MDXGYYOJGPFFJL-QMMMGPOBSA-N N(alpha)-t-butoxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C MDXGYYOJGPFFJL-QMMMGPOBSA-N 0.000 claims 1
- 108091008874 T cell receptors Proteins 0.000 claims 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 1
- QXNRTFWOQVYYSO-UHFFFAOYSA-N [2-(dimethylamino)-2-oxoethyl] 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound CN(C)C(=O)COC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 QXNRTFWOQVYYSO-UHFFFAOYSA-N 0.000 claims 1
- XRQRUIWZNXYPLO-UHFFFAOYSA-N [2-(dimethylamino)-2-oxoethyl] 1-ethyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazine-4-carboxylate Chemical compound CN(C)C(=O)COC(=O)C1=C(NC=2C3=CC=CN=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 XRQRUIWZNXYPLO-UHFFFAOYSA-N 0.000 claims 1
- QZGVRINYJXBYMB-UHFFFAOYSA-N acetyloxymethyl 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(=O)OCOC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CS1 QZGVRINYJXBYMB-UHFFFAOYSA-N 0.000 claims 1
- ULFPSRZPTCFXNE-UHFFFAOYSA-N acetyloxymethyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(=O)OCOC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CS1 ULFPSRZPTCFXNE-UHFFFAOYSA-N 0.000 claims 1
- NEMQQFMSTIEUEF-UHFFFAOYSA-N acetyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound CC(=O)OCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 NEMQQFMSTIEUEF-UHFFFAOYSA-N 0.000 claims 1
- SHNZPOHICPAAKO-UHFFFAOYSA-N acetyloxymethyl 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(=O)OCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CS1 SHNZPOHICPAAKO-UHFFFAOYSA-N 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 claims 1
- 239000000048 adrenergic agonist Substances 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 229940124599 anti-inflammatory drug Drugs 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- LGYUNIWRDMMEGC-UHFFFAOYSA-N benzyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 LGYUNIWRDMMEGC-UHFFFAOYSA-N 0.000 claims 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 1
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
- QMBPUBXPKRTNAM-UHFFFAOYSA-N cyclohexyloxycarbonyloxymethyl 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound C1CCCCC1OC(=O)OCOC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CS1 QMBPUBXPKRTNAM-UHFFFAOYSA-N 0.000 claims 1
- KISFQSUTGWDZJL-UHFFFAOYSA-N cyclohexyloxycarbonyloxymethyl 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-3-ylpyridazine-4-carboxylate Chemical compound C1CCCCC1OC(=O)OCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C=1C=CSC=1 KISFQSUTGWDZJL-UHFFFAOYSA-N 0.000 claims 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- XBFNLCXEXUENEK-UHFFFAOYSA-N fluoromethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound FCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 XBFNLCXEXUENEK-UHFFFAOYSA-N 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 239000003018 immunosuppressive agent Substances 0.000 claims 1
- 229940124589 immunosuppressive drug Drugs 0.000 claims 1
- YQFZWJKPDYIQSF-UHFFFAOYSA-N methylcarbamoyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound CNC(=O)OCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 YQFZWJKPDYIQSF-UHFFFAOYSA-N 0.000 claims 1
- XDVBRIRGFHNDEU-UHFFFAOYSA-N pentan-3-yloxycarbonyloxymethyl 1-ethyl-3-(4-fluorophenyl)-6-oxo-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound O=C1N(CC)N=C(C=2C=CC(F)=CC=2)C(C(=O)OCOC(=O)OC(CC)CC)=C1NC1=CC=CN=C1 XDVBRIRGFHNDEU-UHFFFAOYSA-N 0.000 claims 1
- XKQNDBHMADDVEI-UHFFFAOYSA-N pentanoyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound O=C1N(CC)N=C(C=2C=CC=CC=2)C(C(=O)OCOC(=O)CCCC)=C1NC1=CC=CN=C1 XKQNDBHMADDVEI-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000003367 polycyclic group Chemical group 0.000 claims 1
- DTIJWSGQQVAUKQ-UHFFFAOYSA-N propan-2-yloxycarbonyloxymethyl 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(C)OC(=O)OCOC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CS1 DTIJWSGQQVAUKQ-UHFFFAOYSA-N 0.000 claims 1
- LIHWPNIBLPFFQT-UHFFFAOYSA-N propan-2-yloxycarbonyloxymethyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(C)OC(=O)OCOC(=O)C1=C(NC=2C(=CC=NC=2)C)C(=O)N(CC)N=C1C1=CC=CS1 LIHWPNIBLPFFQT-UHFFFAOYSA-N 0.000 claims 1
- WVQAIUMFSTZFSW-UHFFFAOYSA-N propan-2-yloxycarbonyloxymethyl 1-ethyl-6-oxo-5-(pyridin-3-ylamino)-3-thiophen-2-ylpyridazine-4-carboxylate Chemical compound CC(C)OC(=O)OCOC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=CS1 WVQAIUMFSTZFSW-UHFFFAOYSA-N 0.000 claims 1
- AXIIKTCMTWIDMX-UHFFFAOYSA-N propanoyloxymethyl 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-phenylpyridazine-4-carboxylate Chemical compound CCC(=O)OCOC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 AXIIKTCMTWIDMX-UHFFFAOYSA-N 0.000 claims 1
- ZLLNTGMPSFBHHX-UHFFFAOYSA-N propanoyloxymethyl 1-ethyl-6-oxo-3-phenyl-5-(pyridin-3-ylamino)pyridazine-4-carboxylate Chemical compound O=C1N(CC)N=C(C=2C=CC=CC=2)C(C(=O)OCOC(=O)CC)=C1NC1=CC=CN=C1 ZLLNTGMPSFBHHX-UHFFFAOYSA-N 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 2
- NHYXMAKLBXBVEO-UHFFFAOYSA-N bromomethyl acetate Chemical compound CC(=O)OCBr NHYXMAKLBXBVEO-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 229940076286 cupric acetate Drugs 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NWIJBOCPTGHGIK-UHFFFAOYSA-N quinolin-5-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=N1 NWIJBOCPTGHGIK-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VRDAOVQZVXYRNH-UHFFFAOYSA-N (2-chloropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=CN=C1Cl VRDAOVQZVXYRNH-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CGKKDGMMKSOGLM-UHFFFAOYSA-N 1-chloroethyl acetate Chemical compound CC(Cl)OC(C)=O CGKKDGMMKSOGLM-UHFFFAOYSA-N 0.000 description 1
- KLNFVFGYIVHULZ-UHFFFAOYSA-N 1-chloroethyl carbonochloridate 1-chloroethyl propan-2-yl carbonate Chemical compound CC(Cl)OC(Cl)=O.CC(C)OC(=O)OC(C)Cl KLNFVFGYIVHULZ-UHFFFAOYSA-N 0.000 description 1
- ONZWFHWHTYZZLM-UHFFFAOYSA-N 1-chloroethyl cyclohexyl carbonate Chemical compound CC(Cl)OC(=O)OC1CCCCC1 ONZWFHWHTYZZLM-UHFFFAOYSA-N 0.000 description 1
- YNRHNTGMXINVBO-UHFFFAOYSA-N 1-ethyl-3-(4-methylphenyl)-6-oxo-5-(pyridin-3-ylamino)pyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C=NC=CC=2)C(=O)N(CC)N=C1C1=CC=C(C)C=C1 YNRHNTGMXINVBO-UHFFFAOYSA-N 0.000 description 1
- DUECDWXFOFEPNU-UHFFFAOYSA-N 1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-3-thiophen-3-ylpyridazine-4-carboxylic acid Chemical compound OC(=O)C1=C(NC=2C3=CC=CC=C3C=NC=2)C(=O)N(CC)N=C1C=1C=CSC=1 DUECDWXFOFEPNU-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- YNXRBCVSZYNBCN-UHFFFAOYSA-N 5-[(2-chloropyridin-3-yl)amino]-1-ethyl-6-oxo-3-phenylpyridazine-4-carboxylic acid Chemical compound CCN1C(=O)C(=C(C(=N1)C2=CC=CC=C2)C(=O)O)NC3=C(N=CC=C3)Cl YNXRBCVSZYNBCN-UHFFFAOYSA-N 0.000 description 1
- MABUJKQHZAMOJL-UHFFFAOYSA-N 5-amino-6-oxo-1h-pyridazine-4-carboxylic acid Chemical compound NC1=C(C(O)=O)C=NNC1=O MABUJKQHZAMOJL-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- ADNMSSFNHIKOOR-UHFFFAOYSA-N CCN(C1=O)N=C(C2=CC(C)=CC=C2)C(C(OC(C)(C)OC(C)=O)=O)=C1NC1=CC=CN=C1 Chemical compound CCN(C1=O)N=C(C2=CC(C)=CC=C2)C(C(OC(C)(C)OC(C)=O)=O)=C1NC1=CC=CN=C1 ADNMSSFNHIKOOR-UHFFFAOYSA-N 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- CFOGCYXXNPUMAT-UHFFFAOYSA-N [Na].O=C1C(=C(NO1)C(=O)OCC)C(=O)C=1SC=CC1 Chemical compound [Na].O=C1C(=C(NO1)C(=O)OCC)C(=O)C=1SC=CC1 CFOGCYXXNPUMAT-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- LHUZAYREVYDAGJ-UHFFFAOYSA-N dichloromethane;ethyl acetate;methanol Chemical compound OC.ClCCl.CCOC(C)=O LHUZAYREVYDAGJ-UHFFFAOYSA-N 0.000 description 1
- KBFYJEDFIKOZFW-UHFFFAOYSA-N diethyl carbonate ethyl 3-oxo-3-thiophen-2-ylpropanoate Chemical compound C(OCC)(OCC)=O.O=C(CC(=O)OCC)C=1SC=CC1 KBFYJEDFIKOZFW-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- UXOLDCOJRAMLTQ-ZZXKWVIFSA-N ethyl (2e)-2-chloro-2-hydroxyiminoacetate Chemical compound CCOC(=O)C(\Cl)=N/O UXOLDCOJRAMLTQ-ZZXKWVIFSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200401512A ES2251867B1 (es) | 2004-06-21 | 2004-06-21 | Nuevos derivados de piridazin-3(2h)-ona. |
| PCT/EP2005/006712 WO2005123693A1 (en) | 2004-06-21 | 2005-06-21 | Pyridazin-3(2h)-one derivatives and their use as pde4 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008503531A JP2008503531A (ja) | 2008-02-07 |
| JP2008503531A5 true JP2008503531A5 (enExample) | 2008-08-07 |
Family
ID=34956037
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007517186A Pending JP2008503531A (ja) | 2004-06-21 | 2005-06-21 | ピリダジン−３（２ｈ）−オン誘導体およびｐｄｅ４の阻害剤としてのそれらの使用 |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US20090029996A1 (enExample) |
| EP (1) | EP1781621A1 (enExample) |
| JP (1) | JP2008503531A (enExample) |
| KR (1) | KR20070036137A (enExample) |
| CN (1) | CN1976904A (enExample) |
| AR (1) | AR051738A1 (enExample) |
| AU (1) | AU2005254704A1 (enExample) |
| BR (1) | BRPI0511344A (enExample) |
| CA (1) | CA2570196A1 (enExample) |
| EC (1) | ECSP067057A (enExample) |
| ES (1) | ES2251867B1 (enExample) |
| IL (1) | IL179741A0 (enExample) |
| MX (1) | MXPA06014562A (enExample) |
| NO (1) | NO20070319L (enExample) |
| NZ (1) | NZ551284A (enExample) |
| PE (1) | PE20060531A1 (enExample) |
| RU (1) | RU2386620C2 (enExample) |
| SG (1) | SG155943A1 (enExample) |
| TW (1) | TW200610757A (enExample) |
| UA (1) | UA87691C2 (enExample) |
| WO (1) | WO2005123693A1 (enExample) |
| ZA (1) | ZA200609399B (enExample) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2211344B1 (es) | 2002-12-26 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2251866B1 (es) | 2004-06-18 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| JO2769B1 (en) | 2005-10-26 | 2014-03-15 | جانسين فارماسوتيكا ان. في | Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor |
| JO2849B1 (en) | 2007-02-13 | 2015-03-15 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| ES2320954B1 (es) * | 2007-03-02 | 2010-03-16 | Laboratorio Almirall S.A. | Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona. |
| ES2320955B1 (es) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | Nuevos derivados de 3-((1,2,4)triazolo(4,3-a)piridin-7-il)benzamida. |
| US8700325B2 (en) * | 2007-03-13 | 2014-04-15 | Certusview Technologies, Llc | Marking apparatus and methods for creating an electronic record of marking operations |
| WO2008128996A1 (en) | 2007-04-23 | 2008-10-30 | Janssen Pharmaceutica N.V. | Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists |
| JP5431305B2 (ja) | 2007-04-23 | 2014-03-05 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 高速解離性ドパミン２受容体アンタゴニストとしての４−アルコキシピリダジン誘導体 |
| EP2096105A1 (en) | 2008-02-28 | 2009-09-02 | Laboratorios Almirall, S.A. | Derivatives of 4-(2-amino-1-hydroxyethyl)phenol as agonists of the b2 adrenergic receptor |
| EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| EP2108641A1 (en) | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
| EP2113503A1 (en) | 2008-04-28 | 2009-11-04 | Laboratorios Almirall, S.A. | New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors |
| EP2307374B1 (en) | 2008-07-31 | 2017-01-25 | Janssen Pharmaceutica NV | Piperazin-1-yl-trifluoromethyl-substituted-pyridines as fast dissociating dopamine 2 receptor antagonists |
| UY32297A (es) | 2008-12-22 | 2010-05-31 | Almirall Sa | Sal mesilato de 5-(2-{[6-(2,2-difluoro-2-fenilitoxi) hexil]amino}-1-hidroxietil)-8-hidroxiquinolin-2( 1h)-ona como agonista del receptor b(beta)2 acrenérgico |
| EP2221055A1 (en) | 2009-02-18 | 2010-08-25 | Almirall, S.A. | 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one for the treatment of lung function |
| EP2221297A1 (en) | 2009-02-18 | 2010-08-25 | Almirall, S.A. | 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one and its use in the treatment of pulmonary diseases |
| EP2228368A1 (en) | 2009-03-12 | 2010-09-15 | Almirall, S.A. | Process for manufacturing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one |
| EP2338888A1 (en) | 2009-12-24 | 2011-06-29 | Almirall, S.A. | Imidazopyridine derivatives as JAK inhibitors |
| EP2360158A1 (en) | 2010-02-18 | 2011-08-24 | Almirall, S.A. | Pyrazole derivatives as jak inhibitors |
| UY33213A (es) | 2010-02-18 | 2011-09-30 | Almirall Sa | Derivados de pirazol como inhibidores de jak |
| EP2386555A1 (en) | 2010-05-13 | 2011-11-16 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and m3 muscarinic antagonist activities |
| EP2394998A1 (en) * | 2010-05-31 | 2011-12-14 | Almirall, S.A. | 3-(5-Amino-6-oxo-1,6-dihydropyridazin-3-yl)-biphenyl derivatives as PDE4 inhibitors |
| EP2397482A1 (en) | 2010-06-15 | 2011-12-21 | Almirall, S.A. | Heteroaryl imidazolone derivatives as jak inhibitors |
| EP2441755A1 (en) | 2010-09-30 | 2012-04-18 | Almirall, S.A. | Pyridine- and isoquinoline-derivatives as Syk and JAK kinase inhibitors |
| EP2457900A1 (en) | 2010-11-25 | 2012-05-30 | Almirall, S.A. | New pyrazole derivatives having CRTh2 antagonistic behaviour |
| EP2463289A1 (en) | 2010-11-26 | 2012-06-13 | Almirall, S.A. | Imidazo[1,2-b]pyridazine derivatives as JAK inhibitors |
| EP2489663A1 (en) | 2011-02-16 | 2012-08-22 | Almirall, S.A. | Compounds as syk kinase inhibitors |
| EP2518071A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Imidazopyridine derivatives as PI3K inhibitors |
| EP2518070A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Pyrrolotriazinone derivatives as PI3K inhibitors |
| EP2526945A1 (en) | 2011-05-25 | 2012-11-28 | Almirall, S.A. | New CRTH2 Antagonists |
| EP2527344A1 (en) | 2011-05-25 | 2012-11-28 | Almirall, S.A. | Pyridin-2(1H)-one derivatives useful as medicaments for the treatment of myeloproliferative disorders, transplant rejection, immune-mediated and inflammatory diseases |
| EP2548863A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists. |
| EP2548876A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists |
| EP2554544A1 (en) | 2011-08-01 | 2013-02-06 | Almirall, S.A. | Pyridin-2(1h)-one derivatives as jak inhibitors |
| WO2013052936A1 (en) * | 2011-10-06 | 2013-04-11 | Infersystems Corp. | Automated allocation of media via network |
| EP2578570A1 (en) | 2011-10-07 | 2013-04-10 | Almirall, S.A. | Novel process for preparing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(r)-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one via novel intermediates of synthesis. |
| EP2592078A1 (en) | 2011-11-11 | 2013-05-15 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and M3 muscarinic antagonist activities |
| EP2592077A1 (en) | 2011-11-11 | 2013-05-15 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and M3 muscarinic antagonist activities |
| EP2641900A1 (en) | 2012-03-20 | 2013-09-25 | Almirall, S.A. | Novel polymorphic Crystal forms of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one, heminapadisylate as agonist of the ß2 adrenergic receptor. |
| EP2647627A1 (en) | 2012-04-02 | 2013-10-09 | Almirall, S.A. | Salts of 5-[(1r)-2-({2-[4-(2,2-difluoro-2-phenylethoxy)phenyl] ethyl}amino)-1-hydroxyethyl]-8-hydroxyquinolin-2(1h)-one. |
| EP2666465A1 (en) | 2012-05-25 | 2013-11-27 | Almirall, S.A. | Novel dosage and formulation |
| EP2668941A1 (en) | 2012-05-31 | 2013-12-04 | Almirall, S.A. | Novel dosage form and formulation of abediterol |
| WO2013185284A1 (en) | 2012-06-12 | 2013-12-19 | Abbott Laboratories | Pyridinone and pyridazinone derivatives |
| WO2014060431A1 (en) | 2012-10-16 | 2014-04-24 | Almirall, S.A. | Pyrrolotriazinone derivatives as pi3k inhibitors |
| EP2738172A1 (en) | 2012-11-28 | 2014-06-04 | Almirall, S.A. | New bicyclic compounds as crac channel modulators |
| AU2013363837A1 (en) | 2012-12-17 | 2015-06-11 | Almirall, S.A. | New use of aclidinium |
| AU2013360866A1 (en) | 2012-12-18 | 2015-07-02 | Almirall, S.A. | New cyclohexyl and quinuclidinyl carbamate derivatives having beta2 adrenergic agonist and M3 muscarinic antagonist activity |
| UY35332A (es) | 2013-02-15 | 2014-11-28 | Almirall Sa | Derivados de pirrolotriazina como inhibidores de pi3k |
| TWI643853B (zh) | 2013-02-27 | 2018-12-11 | 阿爾米雷爾有限公司 | 同時具有β2腎上腺素受體促效劑和M3毒蕈鹼受體拮抗劑活性之2-氨基-1-羥乙基-8-羥基喹啉-2(1H)-酮衍生物之鹽類 |
| EP2848615A1 (en) | 2013-07-03 | 2015-03-18 | Almirall, S.A. | New pyrazole derivatives as CRAC channel modulators |
| TWI641373B (zh) | 2013-07-25 | 2018-11-21 | 阿爾米雷爾有限公司 | 具有蕈毒鹼受體拮抗劑和β２腎上腺素受體促效劑二者之活性的２－胺基－１－羥乙基－８－羥基喹啉－２（１Ｈ）－酮衍生物之鹽 |
| TW201517906A (zh) | 2013-07-25 | 2015-05-16 | Almirall Sa | 含有ｍａｂａ化合物和皮質類固醇之組合 |
| TW201617343A (zh) | 2014-09-26 | 2016-05-16 | 阿爾米雷爾有限公司 | 具有β２腎上腺素促效劑及Ｍ３蕈毒拮抗劑活性之新穎雙環衍生物 |
| WO2023008885A1 (ko) * | 2021-07-27 | 2023-02-02 | 보로노이바이오 주식회사 | 피롤로피리미딘 유도체 화합물 및 이의 용도 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5679696A (en) * | 1992-07-28 | 1997-10-21 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic-or heteroatom-containing linking group |
| DE19514568A1 (de) * | 1995-04-20 | 1996-10-24 | Merck Patent Gmbh | Arylalkyl-pyridazinone |
| DE19533975A1 (de) * | 1995-09-14 | 1997-03-20 | Merck Patent Gmbh | Arylalkyl-diazinone |
| DE19540475A1 (de) * | 1995-10-20 | 1997-04-24 | Schering Ag | Chirale Methylphenyloxazolidinone |
| TR199802386T2 (xx) * | 1996-05-20 | 1999-02-22 | Darwin Discovery Limited | Benzofuran karboksamidler ve bunlar�n terap�tik kullan�m�. |
| NZ332341A (en) * | 1996-05-20 | 2000-05-26 | Darwin Discovery Ltd | Quinoline carboxamides as TNF inhibitors and as PDE-IV inhibitors |
| ATE238048T1 (de) * | 1997-11-25 | 2003-05-15 | Warner Lambert Co | Phenolsulfonamide als pde-iv inhibitoren und ihre therapeutische verwendung |
| CA2364653A1 (en) * | 1999-02-25 | 2000-08-31 | Merck Frosst Canada & Co. | Pde iv inhibiting compounds, compositions and methods of treatment |
| CA2742411A1 (en) * | 2000-09-18 | 2002-03-21 | Eisai R&D Management Co., Ltd. | Pyridazinone and triazinone compounds and use thereof as pharmaceutical preparations |
| US6699890B2 (en) * | 2000-12-22 | 2004-03-02 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| CA2463469A1 (en) * | 2001-10-16 | 2003-04-24 | Memory Pharmaceuticals Corporation | 4-(4-alkoxy-3-hydroxyphenyl)-2-pyrrolidone derivatives as pde-4 inhibitors for the treatment of neurological syndromes |
| AR037517A1 (es) * | 2001-11-05 | 2004-11-17 | Novartis Ag | Derivados de naftiridinas, un proceso para su preparacion, composicion farmaceutica y el uso de los mismos para la preparacion de un medicamento para el tratamiento de una enfermedad inflamatoria |
| ES2195785B1 (es) * | 2002-05-16 | 2005-03-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| EP1569908B1 (en) * | 2002-11-19 | 2010-09-15 | Memory Pharmaceuticals Corporation | Pyridine n-oxide compounds as phosphodiesterase 4 inhibitors |
| ES2211344B1 (es) * | 2002-12-26 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| KR20060005375A (ko) * | 2003-04-18 | 2006-01-17 | 메모리 파마슈티칼스 코포레이션 | 포스포디에스테라제 4 억제제로서의 피라졸 유도체 |
| ES2232306B1 (es) * | 2003-11-10 | 2006-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2251866B1 (es) * | 2004-06-18 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2320954B1 (es) * | 2007-03-02 | 2010-03-16 | Laboratorio Almirall S.A. | Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona. |
| EP2674417A3 (en) * | 2007-11-21 | 2014-04-09 | Decode Genetics EHF | Biaryl PDE4 inhibitors for treating inflammation |
-
2004
- 2004-06-21 ES ES200401512A patent/ES2251867B1/es not_active Expired - Fee Related
-
2005
- 2005-06-20 PE PE2005000702A patent/PE20060531A1/es not_active Application Discontinuation
- 2005-06-21 US US11/629,527 patent/US20090029996A1/en not_active Abandoned
- 2005-06-21 EP EP05752744A patent/EP1781621A1/en not_active Withdrawn
- 2005-06-21 AR ARP050102533A patent/AR051738A1/es not_active Application Discontinuation
- 2005-06-21 KR KR1020077001315A patent/KR20070036137A/ko not_active Ceased
- 2005-06-21 JP JP2007517186A patent/JP2008503531A/ja active Pending
- 2005-06-21 WO PCT/EP2005/006712 patent/WO2005123693A1/en not_active Ceased
- 2005-06-21 CA CA002570196A patent/CA2570196A1/en not_active Abandoned
- 2005-06-21 MX MXPA06014562A patent/MXPA06014562A/es not_active Application Discontinuation
- 2005-06-21 TW TW094120704A patent/TW200610757A/zh unknown
- 2005-06-21 UA UAA200700276A patent/UA87691C2/ru unknown
- 2005-06-21 SG SG200906269-6A patent/SG155943A1/en unknown
- 2005-06-21 AU AU2005254704A patent/AU2005254704A1/en not_active Abandoned
- 2005-06-21 BR BRPI0511344-0A patent/BRPI0511344A/pt not_active IP Right Cessation
- 2005-06-21 CN CNA2005800193338A patent/CN1976904A/zh active Pending
- 2005-06-21 RU RU2007102223/04A patent/RU2386620C2/ru not_active IP Right Cessation
- 2005-06-21 NZ NZ551284A patent/NZ551284A/en unknown
-
2006
- 2006-11-13 ZA ZA200609399A patent/ZA200609399B/xx unknown
- 2006-11-30 IL IL179741A patent/IL179741A0/en unknown
- 2006-12-08 EC EC2006007057A patent/ECSP067057A/es unknown
-
2007
- 2007-01-17 NO NO20070319A patent/NO20070319L/no not_active Application Discontinuation
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10759808B2 (en) | Monofunctional intermediates for ligand-dependent target protein degradation | |
| KR102228764B1 (ko) | 키나제 억제제로서의 헤테로시클릭 아미드 | |
| JP6466171B2 (ja) | 新規アミン誘導体またはその塩 | |
| CN102015645B (zh) | 哌啶和吡咯烷化合物 | |
| JP5575799B2 (ja) | ７−フェノキシクロマンカルボン酸誘導体 | |
| JP2008502628A5 (enExample) | ||
| EA005289B1 (ru) | Гетероциклические соединения, содержащие тетрагидропиридиновые или пиперидиновые группы, в качестве антагонистов рецепторов кортикотропин-рилизинг-фактора | |
| JP2008503531A (ja) | ピリダジン−３（２ｈ）−オン誘導体およびｐｄｅ４の阻害剤としてのそれらの使用 | |
| JP2010527951A (ja) | キナーゼ阻害剤としての新規なスルホキシイミン置換型キノリン及びキナゾリン誘導体 | |
| HRP20040392A2 (en) | Heterocyclic compounds for use in the treatment of disorders of the urinary tract | |
| CN108137588B (zh) | 三环稠合吡啶-2-酮衍生物及其作为brd4抑制剂的用途 | |
| CN105001213A (zh) | C-芳基糖苷衍生物、其药物组合物、制备方法及应用 | |
| US20080318941A1 (en) | 4' substituted compounds having 5-ht6 receptor affinity | |
| WO2006118598A1 (en) | Bicycloheteroarylamine compounds as ion channel ligands and uses thereof | |
| JP2005527542A (ja) | キノリンおよびアザインドール誘導体およびその５−ｈｔ６リガンドとしての使用 | |
| US20070185079A1 (en) | Therapeutic agents I | |
| CN101516852B (zh) | 具有5-ht结合特性的喹啉衍生物 | |
| CN107548393B (zh) | 适用于治疗癌症的1-(环)烷基吡啶-2-酮的三环稠合衍生物 | |
| WO2015012400A1 (ja) | グリシントランスポーター阻害物質 | |
| CA3201443A1 (en) | Tetrahydroquinoline derivative and medicinal use thereof | |
| CN110343095A (zh) | 一类精氨酸甲基转移酶抑制剂及其药物组合物和用途 | |
| JPWO2007040166A1 (ja) | 新規な縮合ピロール誘導体 | |
| CN105121424B (zh) | mGluR调节剂 | |
| WO2015060348A1 (ja) | 縮合ピラゾール誘導体 | |
| TW202321232A (zh) | 小分子sting拮抗劑 |