NO318623B1 - Prostaglandin-endoperoksid-H-syntase-biosynteseinhibitorer - Google Patents

Prostaglandin-endoperoksid-H-syntase-biosynteseinhibitorer Download PDF

Info

Publication number: NO318623B1
Authority: NO; Norway
Prior art keywords: hydroxy; phenyl; methyl; pyridazinone; methylsulfonyl
Prior art date: 1998-10-27

Application number

NO20012061A

Other languages

English (en)

Norwegian (no)

Other versions

NO20012061D0 (no

NO20012061L (no

Inventor

Meena V Patel

Lawrence A Black

Anwer Basha

Teodozyj Kolasa

Michael E Kort

Jeffrey J Rohde

Andrew O Stewart

Catherine M Mccarty

Michael J Coghlan

Huaqing Liu

Original Assignee

Abbott Lab

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

2001-04-26

Publication date

2005-04-18

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

2001-04-26 Application filed by Abbott Lab filed Critical Abbott Lab

2001-04-26 Publication of NO20012061D0 publication Critical patent/NO20012061D0/no

2001-06-27 Publication of NO20012061L publication Critical patent/NO20012061L/no

2005-04-18 Publication of NO318623B1 publication Critical patent/NO318623B1/no

Links

150000003180 prostaglandins Chemical class 0.000 title claims description 30
150000001875 compounds Chemical class 0.000 claims abstract description 206
AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims abstract description 12
206010061218 Inflammation Diseases 0.000 claims abstract description 9
230000004054 inflammatory process Effects 0.000 claims abstract description 9
-1 2-hydroxy-2-methyl-propyloxy Chemical group 0.000 claims description 77
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
238000000034 method Methods 0.000 claims description 67
230000015572 biosynthetic process Effects 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 19
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 19
QPTNEZSIWLUDPF-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-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(F)=C1 QPTNEZSIWLUDPF-UHFFFAOYSA-N 0.000 claims description 18
159000000000 sodium salts Chemical class 0.000 claims description 18
239000000651 prodrug Substances 0.000 claims description 17
229940002612 prodrug Drugs 0.000 claims description 17
150000002148 esters Chemical class 0.000 claims description 15
125000005843 halogen group Chemical group 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 13
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 12
239000000460 chlorine Substances 0.000 claims description 12
239000003937 drug carrier Substances 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
239000003795 chemical substances by application Substances 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 8
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 7
125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
GAJBVUJFSOJZDQ-UHFFFAOYSA-N n-[4-[1-(3,4-difluorophenyl)-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(F)C(F)=CC=2)N=C1 GAJBVUJFSOJZDQ-UHFFFAOYSA-N 0.000 claims description 7
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 7
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 7
YGZJJTHSQQJERI-UHFFFAOYSA-N n-[4-[1-(4-fluorophenyl)-5-(3-hydroxy-3-methylbutoxy)-6-oxopyridazin-4-yl]phenyl]sulfonylacetamide Chemical compound C1=CC(S(=O)(=O)NC(=O)C)=CC=C1C1=C(OCCC(C)(C)O)C(=O)N(C=2C=CC(F)=CC=2)N=C1 YGZJJTHSQQJERI-UHFFFAOYSA-N 0.000 claims description 7
GASRXVWUCPPQCN-UHFFFAOYSA-N n-[4-[5-(2-hydroxy-2-methylpropoxy)-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)O)C(=O)N(CC(F)(F)F)N=C1 GASRXVWUCPPQCN-UHFFFAOYSA-N 0.000 claims description 7
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 7
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 5
230000008569 process Effects 0.000 claims description 5
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 4
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 4
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
YELGVOXMDKPKTD-UHFFFAOYSA-N 4-[1-(3,4-difluorophenyl)-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(F)=C1 YELGVOXMDKPKTD-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
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 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
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 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
239000002168 alkylating agent Substances 0.000 claims description 4
229940100198 alkylating agent Drugs 0.000 claims description 4
201000011510 cancer Diseases 0.000 claims description 4
201000008482 osteoarthritis Diseases 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
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
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 3
QRQYHOCFOAOHBK-HXUWFJFHSA-N 2-(3,4-difluorophenyl)-4-[(2s)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 QRQYHOCFOAOHBK-HXUWFJFHSA-N 0.000 claims description 3
KDJWTTCLGKFONX-ZDUSSCGKSA-N 2-(3,4-difluorophenyl)-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(F)=C1 KDJWTTCLGKFONX-ZDUSSCGKSA-N 0.000 claims description 3
COULPBUETDYWQE-UHFFFAOYSA-N 2-(3-chloro-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(Cl)=C1 COULPBUETDYWQE-UHFFFAOYSA-N 0.000 claims description 3
YMUYUABGNBZLOM-UHFFFAOYSA-N 2-(3-chloro-4-fluorophenyl)-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(Cl)=C1 YMUYUABGNBZLOM-UHFFFAOYSA-N 0.000 claims description 3
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 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
NURAWQHKVMNZEZ-UHFFFAOYSA-N 2-(4-fluorophenyl)-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=C1 NURAWQHKVMNZEZ-UHFFFAOYSA-N 0.000 claims description 3
PORJADFRTDGOOL-UHFFFAOYSA-N 2-(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=C1 PORJADFRTDGOOL-UHFFFAOYSA-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
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 3
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 3
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 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
230000000269 nucleophilic effect Effects 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
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 2
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 2
HZRPOYBVCKGWTB-FQEVSTJZSA-N 2-(3,4-dichlorophenyl)-4-[(2r)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(Cl)C(Cl)=C1 HZRPOYBVCKGWTB-FQEVSTJZSA-N 0.000 claims description 2
HZRPOYBVCKGWTB-HXUWFJFHSA-N 2-(3,4-dichlorophenyl)-4-[(2s)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(Cl)C(Cl)=C1 HZRPOYBVCKGWTB-HXUWFJFHSA-N 0.000 claims description 2
QRQYHOCFOAOHBK-FQEVSTJZSA-N 2-(3,4-difluorophenyl)-4-[(2r)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 QRQYHOCFOAOHBK-FQEVSTJZSA-N 0.000 claims description 2
KDJWTTCLGKFONX-CYBMUJFWSA-N 2-(3,4-difluorophenyl)-4-[(2r)-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(F)=C1 KDJWTTCLGKFONX-CYBMUJFWSA-N 0.000 claims description 2
NHGUNUSJGXLYSW-FQEVSTJZSA-N 2-(3-bromo-4-fluorophenyl)-4-[(2r)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(Br)=C1 NHGUNUSJGXLYSW-FQEVSTJZSA-N 0.000 claims description 2
NHGUNUSJGXLYSW-HXUWFJFHSA-N 2-(3-bromo-4-fluorophenyl)-4-[(2s)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(Br)=C1 NHGUNUSJGXLYSW-HXUWFJFHSA-N 0.000 claims description 2
ULTNUHJTUQZSQK-FQEVSTJZSA-N 2-(3-bromophenyl)-4-[(2r)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=CC(Br)=C1 ULTNUHJTUQZSQK-FQEVSTJZSA-N 0.000 claims description 2
ULTNUHJTUQZSQK-HXUWFJFHSA-N 2-(3-bromophenyl)-4-[(2s)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=CC(Br)=C1 ULTNUHJTUQZSQK-HXUWFJFHSA-N 0.000 claims description 2
DINDDYJFKBPWMN-UHFFFAOYSA-N 2-(3-chloro-4-fluorophenyl)-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(Cl)=C1 DINDDYJFKBPWMN-UHFFFAOYSA-N 0.000 claims description 2
CUGVVHOBDSRYOF-FQEVSTJZSA-N 2-(3-chloro-4-fluorophenyl)-4-[(2r)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 CUGVVHOBDSRYOF-FQEVSTJZSA-N 0.000 claims description 2
BCXSVWURMHPDHK-CYBMUJFWSA-N 2-(3-chloro-4-fluorophenyl)-4-[(2r)-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-CYBMUJFWSA-N 0.000 claims description 2
CUGVVHOBDSRYOF-HXUWFJFHSA-N 2-(3-chloro-4-fluorophenyl)-4-[(2s)-2-hydroxy-3-methylbutoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@@H](O)C(C)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(Cl)=C1 CUGVVHOBDSRYOF-HXUWFJFHSA-N 0.000 claims description 2
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 2
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- C07—ORGANIC CHEMISTRY
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- 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
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- 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
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- 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

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

NO20012061A 1998-10-27 2001-04-26 Prostaglandin-endoperoksid-H-syntase-biosynteseinhibitorer NO318623B1 (no)

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 (3)

Publication Number	Publication Date
NO20012061D0 NO20012061D0 (no)	2001-04-26
NO20012061L NO20012061L (no)	2001-06-27
NO318623B1 true NO318623B1 (no)	2005-04-18

Family

ID=27497355

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20012061A NO318623B1 (no)	1998-10-27	2001-04-26	Prostaglandin-endoperoksid-H-syntase-biosynteseinhibitorer

Country Status (19)

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

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU738595B2 (en)	1997-11-19	2001-09-20	Kowa Co., Ltd.	Novel pyridazine derivatives and medicines containing the same as effective ingredients
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
WO2001041760A2 (en)	1999-12-08	2001-06-14	Pharmacia Corporation	Cyclooxygenase-2 inhibitor compositions having rapid onset of therapeutic effect
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
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
TWI290130B (en)	2000-09-15	2007-11-21	Pharmacia Corp	2-Amino-2alkyl-5 heptenoic and heptynoic acid derivatives useful as nitric oxide synthase inhibitors
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
CN100486576C (zh)	2002-02-14	2009-05-13	法玛西雅公司	作为p38map激酶调节剂的取代吡啶酮类
JP2006511606A (ja)	2002-12-13	2006-04-06	ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー	下部尿路症状を治療するα−２−δリガンド
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.
RU2005132167A (ru)	2003-03-18	2006-05-10	Кова Ко., Лтд. (Jp)	Водорастворимые производные фенилпиридазина и лекарственные средства, содержащие их
JP4354984B2 (ja)	2003-05-07	2009-10-28	オステオロジックスエイ／エス	水溶性ストロンチウム塩を用いる軟骨／骨症状の治療
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 (en) *	2006-10-25	2008-04-30	Syngeta Participations AG	Pyridazine derivatives
JP5308350B2 (ja)	2006-12-22	2013-10-09	レコルダーティアイルランドリミテッド	α２δリガンドおよびＮＳＡＩＤを用いた下部尿路機能障害の併用療法
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
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
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)
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)
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
CN101809021B (zh)	2007-09-11	2013-04-24	雅培制药有限公司	八氢-吡咯并[3,4-b]吡咯n-氧化物
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
EP3509604B1 (en)	2016-09-07	2026-02-18	Trustees of Tufts College	Combination therapies using immuno-dash inhibitors and pge2 antagonists
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
WO1982000402A1 (en) *	1980-08-07	1982-02-18	Shamrock Corp Diamond	Herbicidal and plant growth regulant diphenylpyridazinones
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
DE69825154T2 (de) *	1997-03-14	2005-07-21	Merck Frosst Canada & Co, Kirkland	Pyridazinone als inhibitoren von cyclooxygenase-2
PT1005460E (pt) *	1997-08-22	2006-07-31	Abbott Lab	Biossintese de inibidores de prostaglandina-endoperoxido h-sintase
SK286972B6 (sk) *	1997-08-22	2009-08-06	Abbott Laboratories	Arylpyridazinóny ako inhibítory biosyntézy prostaglandín endoperoxid H syntázy, ich použitie a farmaceutická kompozícia s ich obsahom
BR9812127A (pt) *	1997-08-22	2000-07-18	Abbott Lab	Arilpiridazinonas como inibidores da biossìntese de prostagleina endoperóxido h sintase

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

Also Published As

Publication number	Publication date
CN1342149A (zh)	2002-03-27
CA2347982A1 (en)	2000-05-04
EP1124804A1 (en)	2001-08-22
JP2003512292A (ja)	2003-04-02
CZ300570B6 (cs)	2009-06-17
ATE302759T1 (de)	2005-09-15
SK5542001A3 (en)	2001-12-03
WO2000024719A1 (en)	2000-05-04
BR9914858A (pt)	2002-02-05
NO20012061D0 (no)	2001-04-26
BG65261B1 (bg)	2007-10-31
DE69926903D1 (en)	2005-09-29
DK1124804T3 (da)	2005-12-12
CN1279026C (zh)	2006-10-11
NO20012061L (no)	2001-06-27
HK1041876A1 (en)	2002-07-26
PL198503B1 (pl)	2008-06-30
CZ20011481A3 (cs)	2001-09-12
HUP0105248A3 (en)	2002-09-30
KR100666838B1 (ko)	2007-01-11
SK286806B6 (sk)	2009-05-07
EP1124804B1 (en)	2005-08-24
KR20010081101A (ko)	2001-08-27
HK1041876B (en)	2006-06-23
HUP0105248A2 (hu)	2002-07-29
PL349256A1 (en)	2002-07-01
ES2249919T3 (es)	2006-04-01
DE69926903T2 (de)	2006-07-13
BG105523A (en)	2001-12-29
TR200101765T2 (tr)	2002-02-21

Legal Events

Date	Code	Title	Description
2011-05-30	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO318623B1 (no)	2005-04-18	Prostaglandin-endoperoksid-H-syntase-biosynteseinhibitorer
CA2299300C (en)	2007-04-17	Arylpyridazinones as prostaglandin endoperoxide h synthase bisoynthesis inhibitors
US6307047B1 (en)	2001-10-23	Prostaglandin endoperoxide H synthase biosynthesis inhibitors
CA2782453C (en)	2015-11-24	N-linked hydroxamic acid derivatives useful as antibacterial agents
AU2008206441B2 (en)	2014-06-19	N-substituted glycine derivatives: hydroxylase inhibitors
AU2008247102B2 (en)	2011-11-24	2 -pyridine carboxamide derivatives as sodium channel modulators
CA2828337C (en)	2016-05-03	Fluoro-pyridinone derivatives useful as antibacterial agents
MXPA02002111A (es)	2002-10-31	Compuestos de sulfonilfenilpirazol utiles como inhibidores de cox-2.
SK282639B6 (sk)	2002-10-08	(Metylsulfonyl)fenyl-2-(5H)-furanónové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie
EA021025B1 (ru)	2015-03-31	Соединения, эффективные в качестве ингибиторов ксантиноксидазы, способ их получения и содержащая их фармацевтическая композиция
SK170599A3 (en)	2000-05-16	N-hydroxyformamide derivatives as inhibitors of matrix metalloproteinases
AU2003238667B2 (en)	2006-07-20	4-(heterocyclyl)-benzenesulfoximine compounds for the treatment of inflammation
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
AU773237B2 (en)	2004-05-20	Prostaglandin endoperoxide H synthase biosynthesis inhibitors
JPH054366B2 (da)	1993-01-19
MXPA01004247A (en)	2001-12-13	Prostaglandin endoperoxide h synthase biosynthesis inhibitors
MXPA99011772A (en)	2001-05-17	Prostaglandin endoperoxide h synthase biosynthesis inhibitors