SK286806B6 - Pyridazinónové zlúčeniny ako inhibítory cyklooxygenázy, farmaceutická kompozícia s ich obsahom a ich použitie - Google Patents

Pyridazinónové zlúčeniny ako inhibítory cyklooxygenázy, farmaceutická kompozícia s ich obsahom a ich použitie Download PDF

Info

Publication number: SK286806B6
Authority: SK; Slovakia
Prior art keywords: phenyl; hydroxy; pyridazinone; methyl; propoxy
Prior art date: 1998-10-27

Application number

SK554-2001A

Other languages

English (en)

Slovak (sk)

Other versions

SK5542001A3 (en

Inventor

Lawrence A. Black

Anwer Basha

Michael E. Kort

Huaqing Liu

Catherine M. Mccarty

Meena V. Patel

Jeffrey J. Rohde

Michael J. Coghlan

Andrew O. Stewart

Original Assignee

Abbott Laboratories

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.)

1998-10-27

Filing date

1999-10-27

Publication date

2009-05-07

1999-10-27 Application filed by Abbott Laboratories filed Critical Abbott Laboratories

1999-10-27 Priority claimed from US09/427,768 external-priority patent/US6307047B1/en

2001-12-03 Publication of SK5542001A3 publication Critical patent/SK5542001A3/sk

2009-05-07 Publication of SK286806B6 publication Critical patent/SK286806B6/sk

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 8
AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title abstract description 17
239000002599 prostaglandin synthase inhibitor Substances 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 201
206010061218 Inflammation Diseases 0.000 claims abstract description 11
230000004054 inflammatory process Effects 0.000 claims abstract description 11
-1 pyridazinone compound Chemical class 0.000 claims description 379
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
150000003180 prostaglandins Chemical class 0.000 claims description 27
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 24
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 22
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 21
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 19
230000015572 biosynthetic process Effects 0.000 claims description 19
150000002148 esters Chemical class 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 18
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 16
238000004519 manufacturing process Methods 0.000 claims description 14
239000003937 drug carrier Substances 0.000 claims description 9
239000011734 sodium Substances 0.000 claims description 9
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 7
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 7
XNTLXAUHLBBEKP-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 XNTLXAUHLBBEKP-UHFFFAOYSA-N 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 6
229910052708 sodium Inorganic materials 0.000 claims description 5
GEJQAJWDKJZYTC-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-4-(4-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCCC(CO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 GEJQAJWDKJZYTC-UHFFFAOYSA-N 0.000 claims description 4
OQBDNDYDMWPBPJ-UHFFFAOYSA-N 2-(3-chloro-4-fluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 OQBDNDYDMWPBPJ-UHFFFAOYSA-N 0.000 claims description 4
OROAEORJWAZGOL-UHFFFAOYSA-N 2-(4-fluorophenyl)-4-(2-hydroxy-2-methylpropoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C=C1 OROAEORJWAZGOL-UHFFFAOYSA-N 0.000 claims description 4
RTBZTMBBTZKEEF-UHFFFAOYSA-N 4-[1-(3-chloro-4-fluorophenyl)-5-(2-hydroxy-2-methylpropoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCC(C)(O)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 RTBZTMBBTZKEEF-UHFFFAOYSA-N 0.000 claims description 4
VJCMXNBWIGYWIX-UHFFFAOYSA-N 4-[1-(3-chlorophenyl)-5-(2-hydroxy-2-methylpropoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCC(C)(O)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 VJCMXNBWIGYWIX-UHFFFAOYSA-N 0.000 claims description 4
CHEGDWJQDOBZAA-UHFFFAOYSA-N 4-[5-(2-hydroxy-2-methylpropoxy)-6-oxo-1-(2,2,2-trifluoroethyl)pyridazin-4-yl]benzenesulfonamide Chemical compound C1=NN(CC(F)(F)F)C(=O)C(OCC(C)(O)C)=C1C1=CC=C(S(N)(=O)=O)C=C1 CHEGDWJQDOBZAA-UHFFFAOYSA-N 0.000 claims description 4
206010028980 Neoplasm Diseases 0.000 claims description 4
208000002193 Pain Diseases 0.000 claims description 4
206010037660 Pyrexia Diseases 0.000 claims description 4
230000002401 inhibitory effect Effects 0.000 claims description 4
WZRCQBJHCFBYLB-UHFFFAOYSA-N n-[4-[1-(3-chlorophenyl)-5-(2-hydroxy-2-methylpropoxy)-6-oxopyridazin-4-yl]phenyl]sulfonylacetamide Chemical compound C1=CC(S(=O)(=O)NC(=O)C)=CC=C1C1=C(OCC(C)(C)O)C(=O)N(C=2C=C(Cl)C=CC=2)N=C1 WZRCQBJHCFBYLB-UHFFFAOYSA-N 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
LYVAPTCVRNVGCG-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-4-(2-hydroxy-2-methylpropoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(Cl)C(Cl)=C1 LYVAPTCVRNVGCG-UHFFFAOYSA-N 0.000 claims description 3
KNJRLSSPFGSWMD-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(Cl)C(Cl)=C1 KNJRLSSPFGSWMD-UHFFFAOYSA-N 0.000 claims description 3
DIRNSUWKRHPEFO-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-4-(3-hydroxy-2,2-dimethylpropoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCC(C)(CO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 DIRNSUWKRHPEFO-UHFFFAOYSA-N 0.000 claims description 3
BCXSVWURMHPDHK-ZDUSSCGKSA-N 2-(3-chloro-4-fluorophenyl)-4-[(2s)-3-hydroxy-2-methylpropoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@H](CO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 BCXSVWURMHPDHK-ZDUSSCGKSA-N 0.000 claims description 3
GOJYFBBKSWPGBJ-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-(2-hydroxy-2-methylpropoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 GOJYFBBKSWPGBJ-UHFFFAOYSA-N 0.000 claims description 3
UORNLBNMIVTEFR-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-(3-hydroxy-2,2-dimethylpropoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCC(C)(CO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 UORNLBNMIVTEFR-UHFFFAOYSA-N 0.000 claims description 3
FCVOIISBMQGTOB-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 FCVOIISBMQGTOB-UHFFFAOYSA-N 0.000 claims description 3
UDNQXKDRGZYDIY-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-(4-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCCC(CO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 UDNQXKDRGZYDIY-UHFFFAOYSA-N 0.000 claims description 3
FYLYMZGXKFVOKC-AWEZNQCLSA-N 2-(3-chlorophenyl)-4-[(2s)-3-hydroxy-2-methylpropoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@H](CO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 FYLYMZGXKFVOKC-AWEZNQCLSA-N 0.000 claims description 3
YAYLFJDUWAVLET-UHFFFAOYSA-N 4-(3-hydroxy-2,2-dimethylpropoxy)-5-(4-methylsulfonylphenyl)-2-(2,2,2-trifluoroethyl)pyridazin-3-one Chemical compound C1=NN(CC(F)(F)F)C(=O)C(OCC(C)(CO)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 YAYLFJDUWAVLET-UHFFFAOYSA-N 0.000 claims description 3
LNHCYSMDYAEWMK-UHFFFAOYSA-N 4-(3-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)-2-(2,2,2-trifluoroethyl)pyridazin-3-one Chemical compound C1=NN(CC(F)(F)F)C(=O)C(OCCC(C)(O)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 LNHCYSMDYAEWMK-UHFFFAOYSA-N 0.000 claims description 3
MNEXYUFHJMMCFP-UHFFFAOYSA-N 4-[1-(3,4-difluorophenyl)-5-(4-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCCC(CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 MNEXYUFHJMMCFP-UHFFFAOYSA-N 0.000 claims description 3
NDJCLBIATNGXJT-UHFFFAOYSA-N 4-[1-(3-chloro-4-fluorophenyl)-5-(3-hydroxy-2,2-dimethylpropoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCC(C)(CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 NDJCLBIATNGXJT-UHFFFAOYSA-N 0.000 claims description 3
NUAJFABLTXZZNE-UHFFFAOYSA-N 4-[1-(3-chloro-4-fluorophenyl)-5-(4-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCCC(CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 NUAJFABLTXZZNE-UHFFFAOYSA-N 0.000 claims description 3
OCIGQKAAFVCVCX-UHFFFAOYSA-N 4-[1-(3-chlorophenyl)-5-(3-hydroxy-2,2-dimethylpropoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCC(C)(CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 OCIGQKAAFVCVCX-UHFFFAOYSA-N 0.000 claims description 3
HNHRUTLOTCSURC-UHFFFAOYSA-N 4-[1-(3-chlorophenyl)-5-(4-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCCC(CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 HNHRUTLOTCSURC-UHFFFAOYSA-N 0.000 claims description 3
QVZQRROJIOAYOV-ZDUSSCGKSA-N 4-[1-(3-chlorophenyl)-5-[(2s)-3-hydroxy-2-methylpropoxy]-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OC[C@H](CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 QVZQRROJIOAYOV-ZDUSSCGKSA-N 0.000 claims description 3
PZFGDHLPWGDGNM-UHFFFAOYSA-N 4-[1-(4-fluorophenyl)-5-(3-hydroxy-2,2-dimethylpropoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCC(C)(CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C=C1 PZFGDHLPWGDGNM-UHFFFAOYSA-N 0.000 claims description 3
KDYMPGNVZWLCSS-UHFFFAOYSA-N 4-[1-(4-fluorophenyl)-5-(3-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C=C1 KDYMPGNVZWLCSS-UHFFFAOYSA-N 0.000 claims description 3
IFSFJVDLJUEYTQ-UHFFFAOYSA-N 4-[1-(4-fluorophenyl)-5-(4-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCCC(CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C=C1 IFSFJVDLJUEYTQ-UHFFFAOYSA-N 0.000 claims description 3
KRPHJYSRKCFINW-CYBMUJFWSA-N 4-[1-(4-fluorophenyl)-5-[(2r)-3-hydroxy-2-methylpropoxy]-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OC[C@@H](CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C=C1 KRPHJYSRKCFINW-CYBMUJFWSA-N 0.000 claims description 3
DZKMJRYEUVLBJB-UHFFFAOYSA-N 4-[5-(3-hydroxy-2,2-dimethylpropoxy)-6-oxo-1-(2,2,2-trifluoroethyl)pyridazin-4-yl]benzenesulfonamide Chemical compound C1=NN(CC(F)(F)F)C(=O)C(OCC(C)(CO)C)=C1C1=CC=C(S(N)(=O)=O)C=C1 DZKMJRYEUVLBJB-UHFFFAOYSA-N 0.000 claims description 3
DVYCVZLXYUZOGW-UHFFFAOYSA-N 4-[5-(3-hydroxy-3-methylbutoxy)-6-oxo-1-(2,2,2-trifluoroethyl)pyridazin-4-yl]benzenesulfonamide Chemical compound C1=NN(CC(F)(F)F)C(=O)C(OCCC(C)(O)C)=C1C1=CC=C(S(N)(=O)=O)C=C1 DVYCVZLXYUZOGW-UHFFFAOYSA-N 0.000 claims description 3
201000011510 cancer Diseases 0.000 claims description 3
KTEVYFCRLSIJNM-UHFFFAOYSA-N n-[4-[1-(3-chloro-4-fluorophenyl)-5-(2-hydroxy-2-methylpropoxy)-6-oxopyridazin-4-yl]phenyl]sulfonylacetamide Chemical compound C1=CC(S(=O)(=O)NC(=O)C)=CC=C1C1=C(OCC(C)(C)O)C(=O)N(C=2C=C(Cl)C(F)=CC=2)N=C1 KTEVYFCRLSIJNM-UHFFFAOYSA-N 0.000 claims description 3
GWFWRSOKMBUJAV-UHFFFAOYSA-N n-[4-[5-(3-hydroxy-2,2-dimethylpropoxy)-6-oxo-1-(2,2,2-trifluoroethyl)pyridazin-4-yl]phenyl]sulfonylacetamide Chemical compound C1=CC(S(=O)(=O)NC(=O)C)=CC=C1C1=C(OCC(C)(C)CO)C(=O)N(CC(F)(F)F)N=C1 GWFWRSOKMBUJAV-UHFFFAOYSA-N 0.000 claims description 3
201000008482 osteoarthritis Diseases 0.000 claims description 3
ABJNXWDIFBNOSQ-UHFFFAOYSA-N 2-(4-fluorophenyl)-4-(4-hydroxy-2-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCC(CCO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C=C1 ABJNXWDIFBNOSQ-UHFFFAOYSA-N 0.000 claims description 2
UBABAYHEJFXXQR-LLVKDONJSA-N 4-[(2r)-3-hydroxy-2-methylpropoxy]-5-(4-methylsulfonylphenyl)-2-(2,2,2-trifluoroethyl)pyridazin-3-one Chemical compound C1=NN(CC(F)(F)F)C(=O)C(OC[C@@H](CO)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 UBABAYHEJFXXQR-LLVKDONJSA-N 0.000 claims description 2
UBABAYHEJFXXQR-NSHDSACASA-N 4-[(2s)-3-hydroxy-2-methylpropoxy]-5-(4-methylsulfonylphenyl)-2-(2,2,2-trifluoroethyl)pyridazin-3-one Chemical compound C1=NN(CC(F)(F)F)C(=O)C(OC[C@H](CO)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 UBABAYHEJFXXQR-NSHDSACASA-N 0.000 claims description 2
CDUVGFOEOPBRPY-UHFFFAOYSA-N 4-[1-(3,4-difluorophenyl)-5-(3-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 CDUVGFOEOPBRPY-UHFFFAOYSA-N 0.000 claims description 2
YVOPYQGKIKLXNH-UHFFFAOYSA-N 4-[1-(3-chloro-4-fluorophenyl)-5-(3-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 YVOPYQGKIKLXNH-UHFFFAOYSA-N 0.000 claims description 2
LIIBEFMHZVYCNQ-GFCCVEGCSA-N 4-[1-(3-chloro-4-fluorophenyl)-5-[(2r)-3-hydroxy-2-methylpropoxy]-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OC[C@@H](CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 LIIBEFMHZVYCNQ-GFCCVEGCSA-N 0.000 claims description 2
LIIBEFMHZVYCNQ-LBPRGKRZSA-N 4-[1-(3-chloro-4-fluorophenyl)-5-[(2s)-3-hydroxy-2-methylpropoxy]-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OC[C@H](CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 LIIBEFMHZVYCNQ-LBPRGKRZSA-N 0.000 claims description 2
QPVOENXMJUXILD-UHFFFAOYSA-N 4-[1-(3-chlorophenyl)-5-(3-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 QPVOENXMJUXILD-UHFFFAOYSA-N 0.000 claims description 2
QVZQRROJIOAYOV-CYBMUJFWSA-N 4-[1-(3-chlorophenyl)-5-[(2r)-3-hydroxy-2-methylpropoxy]-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OC[C@@H](CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=CC(Cl)=C1 QVZQRROJIOAYOV-CYBMUJFWSA-N 0.000 claims description 2
DECBHVXEYMPHBG-UHFFFAOYSA-N 4-[1-(4-fluorophenyl)-5-(2-hydroxy-2-methylpropoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCC(C)(O)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C=C1 DECBHVXEYMPHBG-UHFFFAOYSA-N 0.000 claims description 2
KRPHJYSRKCFINW-ZDUSSCGKSA-N 4-[1-(4-fluorophenyl)-5-[(2s)-3-hydroxy-2-methylpropoxy]-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OC[C@H](CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C=C1 KRPHJYSRKCFINW-ZDUSSCGKSA-N 0.000 claims description 2
JDKJWJUJNRJKMT-JTQLQIEISA-N 4-[5-[(2s)-3-hydroxy-2-methylpropoxy]-6-oxo-1-(2,2,2-trifluoroethyl)pyridazin-4-yl]benzenesulfonamide Chemical compound C1=NN(CC(F)(F)F)C(=O)C(OC[C@H](CO)C)=C1C1=CC=C(S(N)(=O)=O)C=C1 JDKJWJUJNRJKMT-JTQLQIEISA-N 0.000 claims description 2
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UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
230000035479 physiological effects, processes and functions Effects 0.000 description 1
229940075930 picrate Drugs 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
210000004623 platelet-rich plasma Anatomy 0.000 description 1
210000003281 pleural cavity Anatomy 0.000 description 1
229920002647 polyamide Polymers 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000011591 potassium Chemical class 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
208000026440 premature labor Diseases 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical group CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
239000002089 prostaglandin antagonist Substances 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
238000011160 research Methods 0.000 description 1
ATCCIZURPPEVIZ-SCSAIBSYSA-N roche ester Chemical group COC(=O)[C@H](C)CO ATCCIZURPPEVIZ-SCSAIBSYSA-N 0.000 description 1
239000004248 saffron Substances 0.000 description 1
235000013974 saffron Nutrition 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
229910001958 silver carbonate Inorganic materials 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
BOVHUUQISWANCW-UHFFFAOYSA-M sodium;acetylazanide Chemical compound CC(=O)N[Na] BOVHUUQISWANCW-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000003206 sterilizing agent Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
230000004206 stomach function Effects 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
235000011044 succinic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid group Chemical group C(CCC(=O)O)(=O)O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
125000005305 thiadiazolinyl group Chemical group 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000002769 thiazolinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
CIWZUQUKZAMSIZ-UHFFFAOYSA-N trimethoxy borate Chemical compound COOB(OOC)OOC CIWZUQUKZAMSIZ-UHFFFAOYSA-N 0.000 description 1
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
230000002792 vascular Effects 0.000 description 1
235000019871 vegetable fat Nutrition 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1
239000011787 zinc oxide Substances 0.000 description 1

Classifications

- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
- C07D237/14—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Rheumatology (AREA)
Physical Education & Sports Medicine (AREA)
Pain & Pain Management (AREA)
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Communicable Diseases (AREA)
Immunology (AREA)
Orthopedic Medicine & Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines Containing Plant Substances (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

SK554-2001A 1998-10-27 1999-10-27 Pyridazinónové zlúčeniny ako inhibítory cyklooxygenázy, farmaceutická kompozícia s ich obsahom a ich použitie SK286806B6 (sk)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US17960598A	1998-10-27	1998-10-27
US26187299A	1999-03-03	1999-03-03
US29849099A	1999-04-23	1999-04-23
PCT/US1999/025234 WO2000024719A1 (en)	1998-10-27	1999-10-27	Prostaglandin endoperoxide h synthase biosynthesis inhibitors
US09/427,768 US6307047B1 (en)	1997-08-22	1999-10-27	Prostaglandin endoperoxide H synthase biosynthesis inhibitors

Publications (2)

Publication Number	Publication Date
SK5542001A3 SK5542001A3 (en)	2001-12-03
SK286806B6 true SK286806B6 (sk)	2009-05-07

Family

ID=27497355

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK554-2001A SK286806B6 (sk)	1998-10-27	1999-10-27	Pyridazinónové zlúčeniny ako inhibítory cyklooxygenázy, farmaceutická kompozícia s ich obsahom a ich použitie

Country Status (19)

Country	Link
EP (1)	EP1124804B1 (de)
JP (1)	JP2003512292A (de)
KR (1)	KR100666838B1 (de)
CN (1)	CN1279026C (de)
AT (1)	ATE302759T1 (de)
BG (1)	BG65261B1 (de)
BR (1)	BR9914858A (de)
CA (1)	CA2347982A1 (de)
CZ (1)	CZ300570B6 (de)
DE (1)	DE69926903T2 (de)
DK (1)	DK1124804T3 (de)
ES (1)	ES2249919T3 (de)
HK (1)	HK1041876B (de)
HU (1)	HUP0105248A3 (de)
NO (1)	NO318623B1 (de)
PL (1)	PL198503B1 (de)
SK (1)	SK286806B6 (de)
TR (1)	TR200101765T2 (de)
WO (1)	WO2000024719A1 (de)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1043317B1 (de)	1997-11-19	2009-04-15	Kowa Co., Ltd.	Pyridazinderivate und diese als aktiven bestandteil enthaltende medikamente
TWI241295B (en)	1998-03-02	2005-10-11	Kowa Co	Pyridazine derivative and medicine containing the same as effect component
JP2000247959A (ja)	1999-02-26	2000-09-12	Kowa Co	ピリダジン−３−オン誘導体及びこれを含有する医薬
SK12672001A3 (sk)	1999-12-08	2002-04-04	Pharmacia Corporation	Zloženia inhibítora cyklooxygenázy-2 s rýchlym nástupom terapeutického účinku
US6664256B1 (en)	2000-07-10	2003-12-16	Kowa Co., Ltd.	Phenylpyridazine compounds and medicines containing the same
US6716829B2 (en)	2000-07-27	2004-04-06	Pharmacia Corporation	Aldosterone antagonist and cyclooxygenase-2 inhibitor combination therapy to prevent or treat inflammation-related cardiovascular disorders
AR030741A1 (es)	2000-09-15	2003-09-03	Pharmacia Corp	Derivados de los acidos 2-amino-2-alquil-5-heptenoico y - heptinoico utiles como inhibidores de oxido nitrico sintetasa
AR031129A1 (es)	2000-09-15	2003-09-10	Pharmacia Corp	Derivados de los acidos 2-amino-2-alquil-4-hexenoico y -hexinoico utiles como inhibidores de oxido nitrico sintetasa
US7012098B2 (en)	2001-03-23	2006-03-14	Pharmacia Corporation	Inhibitors of inducible nitric oxide synthase for chemoprevention and treatment of cancers
DE10129320A1 (de)	2001-06-19	2003-04-10	Norbert Mueller	Verwendung von COX-2 Inhibitoren zur Behandlung von Schizophrenie, wahnhaften Störungen, affektiven Störungen oder Ticstörungen
NZ534395A (en)	2002-02-14	2006-10-27	Pharmacia Corp	Substituted pyridinones as modulators of p38 MAP kinase
SI1572173T1 (sl)	2002-12-13	2010-08-31	Warner Lambert Co	Alfa-2-delta ligand za zdravljenje simptomov spodnjega dela sečil
US20040204411A1 (en) *	2002-12-17	2004-10-14	Pharmacia Corporation	Method for the treatment, prevention, or inhibition of a CNS disorder and/or pain and inflammation using a combination of reboxetine and a cyclooxygenase-2 selective inhibitor and compositions thereof
ES2211344B1 (es) *	2002-12-26	2005-10-01	Almirall Prodesfarma, S.A.	Nuevos derivados de piridazin-3(2h)-ona.
EP1604984A1 (de)	2003-03-18	2005-12-14	Kowa Co., Ltd.	Wasserlösliches phenylpyridazinderivat und medikament, das dieses enthält
EP1745791B1 (de)	2003-05-07	2013-06-26	Osteologix A/S	Behandlung von Knorpel/Knochen-Erkrankungen mit wasserlöslichen Strontiumsalzen
ES2251866B1 (es)	2004-06-18	2007-06-16	Laboratorios Almirall S.A.	Nuevos derivados de piridazin-3(2h)-ona.
US7728031B2 (en)	2006-02-24	2010-06-01	Abbott Laboratories	Octahydro-pyrrolo[3,4-b]pyrrole derivatives
EP1916240A1 (de) *	2006-10-25	2008-04-30	Syngeta Participations AG	Neue Pyridazin-Derivate
EA017171B1 (ru)	2006-12-22	2012-10-30	Рекордати Айерленд Лимитед	КОМБИНИРОВАННАЯ ТЕРАПИЯ ЗАБОЛЕВАНИЙ НИЖНИХ МОЧЕВЫВОДЯЩИХ ПУТЕЙ С ИСПОЛЬЗОВАНИЕМ ЛИГАНДОВ αδ И НЕСТЕРОИДНЫХ ПРОТИВОВОСПАЛИТЕЛЬНЫХ ПРЕПАРАТОВ (НПВП)
DE102007008839A1 (de) *	2007-02-23	2008-08-28	Bayer Healthcare Ag	Verfahren zur Herstellung von 4-(3-Hydroxy-3-methyl-butoxy)-5-[4-(methylsulfonyl)phenyl]-2-arylpyridazin-3(2H)-onen
DE102007008840A1 (de)	2007-02-23	2008-08-28	Bayer Healthcare Ag	Neue polymorphe Form von 2-(4-Fluorophenyl)-4-3-hydroxy-3-methyl-1-butoxy)-5-[4-methylsulfonyl)phenyl]-3(2H)-pyridazinon (FHMP)
DE102007008843A1 (de)	2007-02-23	2008-08-28	Bayer Healthcare Ag	Verfahren zur Herstellung von 4,5-Dihalogen-2-aryl-2H-pyridazin-3-onen
DE102007020690A1 (de)	2007-05-03	2008-11-06	Bayer Healthcare Ag	Neue amorphe Form von 2-(4-Fluorophenyl)-4-3-hydroxy-3-mehtyl-1-butoxy)-6[4-methylsulfonyl)phenyl]-3(2H)-pyridazinon (FHMP)
DE102007020689A1 (de)	2007-05-03	2008-11-06	Bayer Healthcare Ag	Neue polymorphe Form von 2-(4-Fluorophenyl)-4-3-hydroxy-3-methyl-1-butoxy-5-[4-methylsulfonyl)phenyl]3/2H)-pyridazinon (FHMP)
DE102007025717A1 (de) *	2007-06-01	2008-12-11	Merck Patent Gmbh	Arylether-pyridazinonderivate
GB0716414D0 (en) *	2007-08-22	2007-10-03	Syngenta Participations Ag	Novel insecticides
EP2188288A1 (de)	2007-09-11	2010-05-26	Abbott Laboratories	Octahydropyrrolo[3,4-b]pyrrol-n-oxide
GB0903493D0 (en)	2009-02-27	2009-04-08	Vantia Ltd	New compounds
JP2012131708A (ja) *	2009-04-28	2012-07-12	Nissan Chem Ind Ltd	４位置換ピリダジノン化合物及びｐ２ｘ７受容体阻害剤
FR2969606B1 (fr) *	2010-12-22	2013-01-11	Pf Medicament	Derives de diarylpyridazinones, leur preparation et leur application en therapeutique humaine
JO3115B1 (ar)	2011-08-22	2017-09-20	Takeda Pharmaceuticals Co	مركبات بيريدازينون واستخدامها كمثبطات daao
US11583516B2 (en)	2016-09-07	2023-02-21	Trustees Of Tufts College	Dash inhibitors, and uses related thereto
CN107334767B (zh) *	2017-06-08	2019-03-05	中国医学科学院医药生物技术研究所	一种哒嗪酮类化合物在肿瘤治疗中的应用
WO2021124344A1 (en) *	2019-12-18	2021-06-24	Abida	Pyridazine derivatives and their use as cyclooxygenase-2 inhibitors

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4238490A (en) *	1979-02-12	1980-12-09	Diamond Shamrock Corporation	Antihypertensive pyridazin(2H)-3-ones
JPS57501328A (de) *	1980-08-07	1982-07-29
US5622948A (en) *	1994-12-01	1997-04-22	Syntex (U.S.A.) Inc.	Pyrrole pyridazine and pyridazinone anti-inflammatory agents
CA2224563A1 (en) *	1995-06-12	1996-12-27	G.D. Searle & Co.	Combination of a cyclooxygenase-2 inhibitor and a leukotriene b4 receptor antagonist for the treatment of inflammations
JP2001514669A (ja) *	1997-03-14	2001-09-11	メルクフロストカナダアンドカンパニー	シクロオキシゲナーゼ−２阻害薬としてのピリダジノン類
DE69833774T2 (de) *	1997-08-22	2007-04-26	Abbott Laboratories, Abbott Park	Prostaglandin endoperoxyde h synthase biosynthese inhibitoren
CA2299300C (en) *	1997-08-22	2007-04-17	Abbott Laboratories	Arylpyridazinones as prostaglandin endoperoxide h synthase bisoynthesis inhibitors
IL133552A (en) *	1997-08-22	2005-12-18	Abbott Lab	Arylpyridazinones as prostaglandin endoperoxide h synthase biosynthesis inhibitors

1999
- 1999-10-27 PL PL349256A patent/PL198503B1/pl not_active IP Right Cessation
- 1999-10-27 WO PCT/US1999/025234 patent/WO2000024719A1/en active Application Filing
- 1999-10-27 CA CA002347982A patent/CA2347982A1/en not_active Abandoned
- 1999-10-27 CZ CZ20011481A patent/CZ300570B6/cs not_active IP Right Cessation
- 1999-10-27 ES ES99953259T patent/ES2249919T3/es not_active Expired - Lifetime
- 1999-10-27 TR TR2001/01765T patent/TR200101765T2/xx unknown
- 1999-10-27 SK SK554-2001A patent/SK286806B6/sk not_active IP Right Cessation
- 1999-10-27 EP EP99953259A patent/EP1124804B1/de not_active Expired - Lifetime
- 1999-10-27 BR BR9914858-7A patent/BR9914858A/pt not_active IP Right Cessation
- 1999-10-27 CN CNB998147265A patent/CN1279026C/zh not_active Expired - Fee Related
- 1999-10-27 DK DK99953259T patent/DK1124804T3/da active
- 1999-10-27 JP JP2000578289A patent/JP2003512292A/ja not_active Ceased
- 1999-10-27 KR KR1020017005342A patent/KR100666838B1/ko not_active IP Right Cessation
- 1999-10-27 AT AT99953259T patent/ATE302759T1/de not_active IP Right Cessation
- 1999-10-27 DE DE69926903T patent/DE69926903T2/de not_active Expired - Lifetime
- 1999-10-27 HU HU0105248A patent/HUP0105248A3/hu unknown
2001
- 2001-04-26 NO NO20012061A patent/NO318623B1/no not_active IP Right Cessation
- 2001-05-19 BG BG105523A patent/BG65261B1/bg unknown
2002
- 2002-02-19 HK HK02101207.5A patent/HK1041876B/zh not_active IP Right Cessation

Also Published As

Publication number	Publication date
HK1041876B (zh)	2006-06-23
CA2347982A1 (en)	2000-05-04
NO318623B1 (no)	2005-04-18
JP2003512292A (ja)	2003-04-02
TR200101765T2 (tr)	2002-02-21
SK5542001A3 (en)	2001-12-03
EP1124804B1 (de)	2005-08-24
HUP0105248A2 (hu)	2002-07-29
NO20012061D0 (no)	2001-04-26
PL198503B1 (pl)	2008-06-30
KR100666838B1 (ko)	2007-01-11
CN1342149A (zh)	2002-03-27
ES2249919T3 (es)	2006-04-01
BG105523A (en)	2001-12-29
EP1124804A1 (de)	2001-08-22
DE69926903T2 (de)	2006-07-13
CZ20011481A3 (cs)	2001-09-12
ATE302759T1 (de)	2005-09-15
BG65261B1 (bg)	2007-10-31
BR9914858A (pt)	2002-02-05
CN1279026C (zh)	2006-10-11
DK1124804T3 (da)	2005-12-12
HK1041876A1 (en)	2002-07-26
WO2000024719A1 (en)	2000-05-04
DE69926903D1 (en)	2005-09-29
CZ300570B6 (cs)	2009-06-17
KR20010081101A (ko)	2001-08-27
PL349256A1 (en)	2002-07-01
HUP0105248A3 (en)	2002-09-30
NO20012061L (no)	2001-06-27

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EP1206474B1 (de)	2004-05-26	Als cox-hemmer verwendbare sulfonylphenylpyrazol-verbindungen
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US6472416B1 (en)	2002-10-29	Sulfonylphenylpyrazole compounds useful as COX-2 inhibitors
JP2001514669A (ja)	2001-09-11	シクロオキシゲナーゼ−２阻害薬としてのピリダジノン類
JP4559849B2 (ja)	2010-10-13	置換２−フェニル−３（２ｈ）−ピリダジノン
BRPI0615285A2 (pt)	2011-05-17	composto, processo para a sua preparação, composição farmacêutica que o compreende, sua utilização, e métodos para o tratamento de um distúrbio metabólico, diabetes, obesidade ou sìndrome metabólica
JP2002212179A (ja)	2002-07-31	新規アニリド誘導体又はその塩及びこれを含有する医薬
CZ300847B6 (cs)	2009-08-26	Arylpyridazinony jako inhibitory biosyntézy prostaglandin endoperoxid H synthasy, jejich použití a farmaceutická kompozice s jejich obsahem
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2011-07-06	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20101027