ZA200409173B - Pyridazin-3(2H)-one derivatives as PDE4 inhibitors. - Google Patents

Pyridazin-3(2H)-one derivatives as PDE4 inhibitors. Download PDF

Info

Publication number: ZA200409173B
Authority: ZA; South Africa
Prior art keywords: acetyl; amino; ethyl; phenylpyridazin; phenyl
Prior art date: 2002-05-16

Application number

ZA200409173A

Other languages

English (en)

Inventor

Vittorio Dal Piaz

Claudia Vergeli

Maria Paola Giovannoni

Nuria Aguilar Izquierdo

Original Assignee

Almirall Prodesfarma Sa

Priority date (The priority date 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 date listed.)

2002-05-16

Filing date

2004-11-11

Publication date

2005-07-29

2004-11-11 Application filed by Almirall Prodesfarma Sa filed Critical Almirall Prodesfarma Sa

2005-07-29 Publication of ZA200409173B publication Critical patent/ZA200409173B/en

Links

AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title claims description 38
229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title description 5
239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 182
150000001875 compounds Chemical class 0.000 claims description 65
-1 cyano, difluoromethoxy Chemical group 0.000 claims description 46
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
125000001424 substituent group Chemical group 0.000 claims description 42
125000000217 alkyl group Chemical group 0.000 claims description 41
238000000034 method Methods 0.000 claims description 39
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 33
125000003545 alkoxy group Chemical group 0.000 claims description 33
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 30
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 26
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
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 description 22
102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims description 22
108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims description 22
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
239000000203 mixture Substances 0.000 claims description 21
125000004414 alkyl thio group Chemical group 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 18
238000011282 treatment Methods 0.000 claims description 18
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 16
VROMXVIODDASTK-UHFFFAOYSA-N 5-amino-1h-pyridazin-6-one Chemical class NC1=CC=NNC1=O VROMXVIODDASTK-UHFFFAOYSA-N 0.000 claims description 16
239000005711 Benzoic acid Substances 0.000 claims description 16
235000010233 benzoic acid Nutrition 0.000 claims description 16
125000005843 halogen group Chemical group 0.000 claims description 15
230000008569 process Effects 0.000 claims description 15
125000003118 aryl group Chemical group 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 14
125000002252 acyl group Chemical group 0.000 claims description 13
230000005764 inhibitory process Effects 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
201000010099 disease Diseases 0.000 claims description 11
230000001575 pathological effect Effects 0.000 claims description 11
125000004442 acylamino group Chemical group 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
125000005530 alkylenedioxy group Chemical group 0.000 claims description 9
150000001412 amines Chemical class 0.000 claims description 9
125000000000 cycloalkoxy group Chemical group 0.000 claims description 9
125000002947 alkylene group Chemical group 0.000 claims description 8
125000004104 aryloxy group Chemical group 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
125000004663 dialkyl amino group Chemical group 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
239000000126 substance Substances 0.000 claims description 7
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000004043 oxo group Chemical group O=* 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
206010012438 Dermatitis atopic Diseases 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
201000004681 Psoriasis Diseases 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 4
201000008937 atopic dermatitis Diseases 0.000 claims description 4
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
125000003107 substituted aryl group Chemical group 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
CIRJLWJPICQIAQ-UHFFFAOYSA-N 4-[[5-acetyl-6-(3-chlorophenyl)-2-ethyl-3-oxopyridazin-4-yl]amino]benzoic acid Chemical compound CC(=O)C1=C(NC=2C=CC(=CC=2)C(O)=O)C(=O)N(CC)N=C1C1=CC=CC(Cl)=C1 CIRJLWJPICQIAQ-UHFFFAOYSA-N 0.000 claims description 3
GGVPOCCNCPBSNB-UHFFFAOYSA-N 5-acetyl-4-(3-chloroanilino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C(Cl)C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 GGVPOCCNCPBSNB-UHFFFAOYSA-N 0.000 claims description 3
ANLZZGTWBDRRPB-UHFFFAOYSA-N 5-nitro-1h-pyridazin-6-one Chemical class [O-][N+](=O)C1=CC=NNC1=O ANLZZGTWBDRRPB-UHFFFAOYSA-N 0.000 claims description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
239000005864 Sulphur Chemical group 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 3
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
125000002950 monocyclic group Chemical group 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
239000001301 oxygen Chemical group 0.000 claims description 3
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
JGSIAOZAXBWRFO-UHFFFAOYSA-N 3-methylsulfanyl-1-phenyl-4,5-dihydrobenzo[g]indazole Chemical compound C1CC2=CC=CC=C2C2=C1C(SC)=NN2C1=CC=CC=C1 JGSIAOZAXBWRFO-UHFFFAOYSA-N 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
DAFCVMJHEGNTLP-UHFFFAOYSA-N 5-acetyl-2-ethyl-4-(naphthalen-1-ylamino)-6-(3-nitrophenyl)pyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C3=CC=CC=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC([N+]([O-])=O)=C1 DAFCVMJHEGNTLP-UHFFFAOYSA-N 0.000 claims description 2
LUBJCRLGQSPQNN-UHFFFAOYSA-N Z-phenylurea Natural products NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
229960004889 salicylic acid Drugs 0.000 claims description 2
WPYMKLBDIGXBTP-VQEHIDDOSA-N benzoic acid Chemical compound OC(=O)C1=CC=C[13CH]=C1 WPYMKLBDIGXBTP-VQEHIDDOSA-N 0.000 claims 5
WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 claims 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
NSTHBWMOVHGUIZ-UHFFFAOYSA-N 3-[4-acetyl-5-(3,5-difluoroanilino)-1-ethyl-6-oxopyridazin-3-yl]benzonitrile Chemical compound CC(=O)C1=C(NC=2C=C(F)C=C(F)C=2)C(=O)N(CC)N=C1C1=CC=CC(C#N)=C1 NSTHBWMOVHGUIZ-UHFFFAOYSA-N 0.000 claims 1
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
ABGIZJDDHLAZFB-UHFFFAOYSA-N 4-[(5-acetyl-2-ethyl-3-oxo-6-phenylpyridazin-4-yl)amino]benzenesulfonamide Chemical compound CC(=O)C1=C(NC=2C=CC(=CC=2)S(N)(=O)=O)C(=O)N(CC)N=C1C1=CC=CC=C1 ABGIZJDDHLAZFB-UHFFFAOYSA-N 0.000 claims 1
PYSDBLJXOCDXRH-UHFFFAOYSA-N 5-(3-cyanoanilino)-1-ethyl-6-oxo-3-phenylpyridazine-4-carboxamide;5-(3-cyanoanilino)-1-ethyl-6-oxo-3-phenylpyridazine-4-carboxylic acid Chemical compound NC(=O)C1=C(NC=2C=C(C=CC=2)C#N)C(=O)N(CC)N=C1C1=CC=CC=C1.OC(=O)C1=C(NC=2C=C(C=CC=2)C#N)C(=O)N(CC)N=C1C1=CC=CC=C1 PYSDBLJXOCDXRH-UHFFFAOYSA-N 0.000 claims 1
LOIHYMRYBPPGAS-UHFFFAOYSA-N 5-acetyl-2-cyclobutyl-4-(3,5-dichloroanilino)-6-phenylpyridazin-3-one Chemical compound O=C1N(C2CCC2)N=C(C=2C=CC=CC=2)C(C(=O)C)=C1NC1=CC(Cl)=CC(Cl)=C1 LOIHYMRYBPPGAS-UHFFFAOYSA-N 0.000 claims 1
ZHZCDCFXXIUELX-UHFFFAOYSA-N 5-acetyl-2-ethyl-4-(2-methoxyanilino)-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C(=CC=CC=2)OC)C(=O)N(CC)N=C1C1=CC=CC=C1 ZHZCDCFXXIUELX-UHFFFAOYSA-N 0.000 claims 1
GKDQLKGXMFBCGV-UHFFFAOYSA-N 5-acetyl-4-(2,5-dimethoxyanilino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C(=CC=C(OC)C=2)OC)C(=O)N(CC)N=C1C1=CC=CC=C1 GKDQLKGXMFBCGV-UHFFFAOYSA-N 0.000 claims 1
QRAHDPXJBHBZSK-UHFFFAOYSA-N 5-acetyl-4-(2-chloroanilino)-2-ethyl-6-phenylpyridazin-3-one;5-acetyl-2-ethyl-4-(naphthalen-1-ylamino)-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C(=CC=CC=2)Cl)C(=O)N(CC)N=C1C1=CC=CC=C1.CC(=O)C1=C(NC=2C3=CC=CC=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 QRAHDPXJBHBZSK-UHFFFAOYSA-N 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/22—Nitrogen and oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

ZA200409173A 2002-05-16 2004-11-11 Pyridazin-3(2H)-one derivatives as PDE4 inhibitors. ZA200409173B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
ES200201111A ES2195785B1 (es)	2002-05-16	2002-05-16	Nuevos derivados de piridazin-3(2h)-ona.

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US (2)	US7459453B2 (ja)
EP (1)	EP1503992A1 (ja)
JP (1)	JP2005533024A (ja)
KR (1)	KR20040106536A (ja)
CN (1)	CN1324014C (ja)
AR (1)	AR040076A1 (ja)
AU (1)	AU2003236648A1 (ja)
BR (1)	BR0310106A (ja)
CA (1)	CA2485896A1 (ja)
EC (1)	ECSP045410A (ja)
ES (1)	ES2195785B1 (ja)
IL (1)	IL165173A0 (ja)
MX (1)	MXPA04011209A (ja)
MY (1)	MY132106A (ja)
NO (1)	NO20045461L (ja)
NZ (1)	NZ536604A (ja)
PE (1)	PE20040689A1 (ja)
RU (1)	RU2326869C2 (ja)
TW (1)	TWI309981B (ja)
UA (1)	UA77532C2 (ja)
UY (1)	UY27807A1 (ja)
WO (1)	WO2003097613A1 (ja)
ZA (1)	ZA200409173B (ja)

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ES2165768B1 (es)	1999-07-14	2003-04-01	Almirall Prodesfarma Sa	Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen.
US7214687B2 (en)	1999-07-14	2007-05-08	Almirall Ag	Quinuclidine derivatives and medicinal compositions containing the same
ES2211344B1 (es)	2002-12-26	2005-10-01	Almirall Prodesfarma, S.A.	Nuevos derivados de piridazin-3(2h)-ona.
JP4978192B2 (ja) *	2004-04-01	2012-07-18	アステラス製薬株式会社	ピラジン誘導体およびその医薬的使用
AU2005245580A1 (en) *	2004-05-19	2005-12-01	Basf Aktiengesellschaft	2-substituted pyrimidines and their use as pesticides
CA2568571C (en)	2004-05-31	2012-12-18	Almirall Prodesfarma S.A.	Combinations comprising antimuscarinic agents and corticosteroids
ES2257152B1 (es)	2004-05-31	2007-07-01	Laboratorios Almirall S.A.	Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos.
ES2251866B1 (es) *	2004-06-18	2007-06-16	Laboratorios Almirall S.A.	Nuevos derivados de piridazin-3(2h)-ona.
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2002
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TW200400033A (en)	2004-01-01
AR040076A1 (es)	2005-03-16
JP2005533024A (ja)	2005-11-04
MXPA04011209A (es)	2005-02-14
CN1668603A (zh)	2005-09-14
NZ536604A (en)	2006-07-28
UY27807A1 (es)	2003-11-28
BR0310106A (pt)	2005-02-22
ES2195785B1 (es)	2005-03-16
IL165173A0 (en)	2005-12-18
AU2003236648A1 (en)	2003-12-02
WO2003097613A1 (en)	2003-11-27
UA77532C2 (en)	2006-12-15
RU2004136977A (ru)	2005-07-10
TWI309981B (en)	2009-05-21
US7459453B2 (en)	2008-12-02
RU2326869C2 (ru)	2008-06-20
PE20040689A1 (es)	2004-10-08
EP1503992A1 (en)	2005-02-09
ES2195785A1 (es)	2003-12-01
CA2485896A1 (en)	2003-11-27
CN1324014C (zh)	2007-07-04
NO20045461L (no)	2005-01-19
KR20040106536A (ko)	2004-12-17
US20080269235A1 (en)	2008-10-30
ECSP045410A (es)	2005-01-03
US20060052379A1 (en)	2006-03-09
MY132106A (en)	2007-09-28

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EP1758869B1 (en)	2010-12-22	Pyridazin-3(2h)-one derivatives and their use as pde4 inhibitors
US20090029996A1 (en)	2009-01-29	Pyridazin-3(2H)-One Derivatives And Their Use As Pde4 Inhibitors
JP4328018B2 (ja)	2009-09-09	新規ピリダジン誘導体及びこれを有効成分とする医薬
MXPA06005101A (en)	2006-10-17	Pyridazin-3 (2h) -one derivatives and their use as pde4 inhibitors