ZA200302346B - New thiadiazoles and oxadiazoles and their use as phosphodiesterase-7 inhibitors. - Google Patents

New thiadiazoles and oxadiazoles and their use as phosphodiesterase-7 inhibitors. Download PDF

Info

Publication number: ZA200302346B
Authority: ZA; South Africa
Prior art keywords: methyl; thiadiazol; dihydro; cyclohexylimino; phenyl
Prior art date: 2000-10-02

Application number

ZA200302346A

Other languages

English (en)

Inventor

Fabrice Vergne

Pierre Ducrot

Charles Andrianjara

Patrick Bernadelli

Edwige Lorthiois

Original Assignee

Warner Lambert Co

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.)

2000-10-02

Filing date

2003-03-26

Publication date

2004-08-04

2003-03-26 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2004-08-04 Publication of ZA200302346B publication Critical patent/ZA200302346B/en

Links

239000002606 phosphodiesterase VII inhibitor Substances 0.000 title claims description 11
150000004867 thiadiazoles Chemical class 0.000 title description 3
150000004866 oxadiazoles Chemical class 0.000 title description 2
-1 5-trifluoromethyl-2H-[1,2,4]triazol-3- ylimino Chemical group 0.000 claims description 153
150000001875 compounds Chemical class 0.000 claims description 99
125000000217 alkyl group Chemical group 0.000 claims description 64
125000000623 heterocyclic group Chemical group 0.000 claims description 63
229910052799 carbon Inorganic materials 0.000 claims description 43
125000000753 cycloalkyl group Chemical group 0.000 claims description 39
229910052736 halogen Inorganic materials 0.000 claims description 39
125000002947 alkylene group Chemical group 0.000 claims description 38
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 37
150000002367 halogens Chemical class 0.000 claims description 35
125000003118 aryl group Chemical group 0.000 claims description 33
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 27
125000000392 cycloalkenyl group Chemical group 0.000 claims description 27
125000004450 alkenylene group Chemical group 0.000 claims description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
125000001188 haloalkyl group Chemical group 0.000 claims description 23
125000003367 polycyclic group Chemical group 0.000 claims description 22
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 20
238000006243 chemical reaction Methods 0.000 claims description 20
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 19
150000001412 amines Chemical class 0.000 claims description 18
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 claims description 15
201000010099 disease Diseases 0.000 claims description 15
239000005711 Benzoic acid Substances 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 14
238000000034 method Methods 0.000 claims description 14
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 14
125000003342 alkenyl group Chemical group 0.000 claims description 12
125000000304 alkynyl group Chemical group 0.000 claims description 12
125000002619 bicyclic group Chemical group 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 11
125000004419 alkynylene group Chemical group 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 10
PAFZNILMFXTMIY-UHFFFAOYSA-N Cyclohexylamine Natural products NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 9
229940123304 Phosphodiesterase 7 inhibitor Drugs 0.000 claims description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 8
125000000732 arylene group Chemical group 0.000 claims description 8
125000002993 cycloalkylene group Chemical group 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
ILAXBOIRSPXAMM-UHFFFAOYSA-N methyl n-aminocarbamodithioate Chemical compound CSC(=S)NN ILAXBOIRSPXAMM-UHFFFAOYSA-N 0.000 claims description 7
208000030507 AIDS Diseases 0.000 claims description 6
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
150000003583 thiosemicarbazides Chemical class 0.000 claims description 6
210000001744 T-lymphocyte Anatomy 0.000 claims description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 5
150000002429 hydrazines Chemical class 0.000 claims description 5
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
229960001867 guaiacol Drugs 0.000 claims description 4
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
208000023504 respiratory system disease Diseases 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
WDUPXXTYSQUFPJ-UHFFFAOYSA-N 3-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)benzamide Chemical compound CN1N=C(C=2C=C(C=CC=2)C(N)=O)SC1=NC1CCCCC1 WDUPXXTYSQUFPJ-UHFFFAOYSA-N 0.000 claims description 3
NLINLEVJNCVGEZ-UHFFFAOYSA-N 4-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)benzonitrile Chemical compound CN1N=C(C=2C=CC(=CC=2)C#N)SC1=NC1CCCCC1 NLINLEVJNCVGEZ-UHFFFAOYSA-N 0.000 claims description 3
208000023275 Autoimmune disease Diseases 0.000 claims description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
206010028980 Neoplasm Diseases 0.000 claims description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 3
206010052779 Transplant rejections Diseases 0.000 claims description 3
208000026935 allergic disease Diseases 0.000 claims description 3
208000006673 asthma Diseases 0.000 claims description 3
201000011510 cancer Diseases 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
230000002124 endocrine Effects 0.000 claims description 3
230000007717 exclusion Effects 0.000 claims description 3
210000003020 exocrine pancreas Anatomy 0.000 claims description 3
208000027866 inflammatory disease Diseases 0.000 claims description 3
150000002540 isothiocyanates Chemical class 0.000 claims description 3
201000008482 osteoarthritis Diseases 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
208000024691 pancreas disease Diseases 0.000 claims description 3
208000011580 syndromic disease Diseases 0.000 claims description 3
SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 claims description 3
208000009935 visceral pain Diseases 0.000 claims description 3
XPNJUASZEPIKFA-UHFFFAOYSA-N 2-[(3,5-diphenyl-1,3,4-thiadiazol-2-ylidene)amino]-1,4-diphenylbut-2-ene-1,4-dione Chemical compound C=1C=CC=CC=1C(=O)C=C(C(=O)C=1C=CC=CC=1)N=C1SC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 XPNJUASZEPIKFA-UHFFFAOYSA-N 0.000 claims description 2
DHNRSEQFXUYVPS-UHFFFAOYSA-N 2-chloro-5-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)benzamide Chemical compound CN1N=C(C=2C=C(C(Cl)=CC=2)C(N)=O)SC1=NC1CCCCC1 DHNRSEQFXUYVPS-UHFFFAOYSA-N 0.000 claims description 2
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
RFWDXHYWMXMTSV-UHFFFAOYSA-N 3-[(5-cyclohexyl-3-methyl-1,3,4-thiadiazol-2-ylidene)amino]benzoic acid Chemical compound CN1N=C(C2CCCCC2)SC1=NC1=CC=CC(C(O)=O)=C1 RFWDXHYWMXMTSV-UHFFFAOYSA-N 0.000 claims description 2
BHXLYBRKINDRDO-UHFFFAOYSA-N 3-[[5-(4-chlorophenyl)-3-methyl-1,3,4-thiadiazol-2-ylidene]amino]-4-hydroxybenzoic acid Chemical compound CN1N=C(C=2C=CC(Cl)=CC=2)SC1=NC1=CC(C(O)=O)=CC=C1O BHXLYBRKINDRDO-UHFFFAOYSA-N 0.000 claims description 2
MUZWYUALDIIJKU-UHFFFAOYSA-N 4-(5-cyclohex-3-en-1-ylimino-4-methyl-1,3,4-thiadiazol-2-yl)benzamide Chemical compound CN1N=C(C=2C=CC(=CC=2)C(N)=O)SC1=NC1CCC=CC1 MUZWYUALDIIJKU-UHFFFAOYSA-N 0.000 claims description 2
JEJBLLHMDLAENE-UHFFFAOYSA-N 4-(5-cyclohexylimino-4-methyl-1,3,4-oxadiazol-2-yl)benzamide Chemical compound CN1N=C(C=2C=CC(=CC=2)C(N)=O)OC1=NC1CCCCC1 JEJBLLHMDLAENE-UHFFFAOYSA-N 0.000 claims description 2
JYDUCTYSUKBEJA-UHFFFAOYSA-N 4-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)-n-(2-ethylpyrazol-3-yl)benzamide Chemical compound CCN1N=CC=C1NC(=O)C1=CC=C(C=2SC(=NC3CCCCC3)N(C)N=2)C=C1 JYDUCTYSUKBEJA-UHFFFAOYSA-N 0.000 claims description 2
MLQLLPVQUQSOGV-UHFFFAOYSA-N 4-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)benzoic acid Chemical compound CN1N=C(C=2C=CC(=CC=2)C(O)=O)SC1=NC1CCCCC1 MLQLLPVQUQSOGV-UHFFFAOYSA-N 0.000 claims description 2
POMCEBRLBHAHKV-UHFFFAOYSA-N 4-[4-methyl-5-(3-oxocyclohexyl)imino-1,3,4-thiadiazol-2-yl]benzamide Chemical compound CN1N=C(C=2C=CC(=CC=2)C(N)=O)SC1=NC1CCCC(=O)C1 POMCEBRLBHAHKV-UHFFFAOYSA-N 0.000 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
DKYWZPJMHKCOHC-UHFFFAOYSA-N 5-(4-chlorophenyl)-3-methyl-n-propan-2-yl-1,3,4-thiadiazol-2-imine Chemical compound CN1C(=NC(C)C)SC(C=2C=CC(Cl)=CC=2)=N1 DKYWZPJMHKCOHC-UHFFFAOYSA-N 0.000 claims description 2
UBKURFHJNUIRBY-UHFFFAOYSA-N 5-[(5-cyclohexyl-3-methyl-1,3,4-thiadiazol-2-ylidene)amino]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1N=C1N(C)N=C(C2CCCCC2)S1 UBKURFHJNUIRBY-UHFFFAOYSA-N 0.000 claims description 2
DYQQZSOTLIPYBH-JNSHFYNHSA-N C1C[C@@H](C)CC[C@H]1N=C1N(C)N=C(C=2C=CC(=CC=2)C#N)S1 Chemical compound C1C[C@@H](C)CC[C@H]1N=C1N(C)N=C(C=2C=CC(=CC=2)C#N)S1 DYQQZSOTLIPYBH-JNSHFYNHSA-N 0.000 claims description 2
241000124008 Mammalia Species 0.000 claims description 2
150000001263 acyl chlorides Chemical class 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
229910052792 caesium Inorganic materials 0.000 claims description 2
239000004202 carbamide Substances 0.000 claims description 2
UPLUFASLXPWQHZ-UHFFFAOYSA-N dimethyl 2-[[5-benzoyl-3-(4-methylphenyl)-1,3,4-thiadiazol-2-ylidene]amino]but-2-enedioate Chemical compound COC(=O)C=C(C(=O)OC)N=C1SC(C(=O)C=2C=CC=CC=2)=NN1C1=CC=C(C)C=C1 UPLUFASLXPWQHZ-UHFFFAOYSA-N 0.000 claims description 2
150000002148 esters Chemical class 0.000 claims description 2
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
210000004153 islets of langerhan Anatomy 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
WEIRZYTXAXQVPU-UHFFFAOYSA-N methyl 2-chloro-4-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C(S1)=NN(C)C1=NC1CCCCC1 WEIRZYTXAXQVPU-UHFFFAOYSA-N 0.000 claims description 2
PFBBNMXEKXLYRD-UHFFFAOYSA-N methyl 4-(5-cyclohexylimino-4-methyl-1,3,4-oxadiazol-2-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(O1)=NN(C)C1=NC1CCCCC1 PFBBNMXEKXLYRD-UHFFFAOYSA-N 0.000 claims description 2
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
HMLIQWYFUWNFED-UHFFFAOYSA-N n-[4-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C(S1)=NN(C)C1=NC1CCCCC1 HMLIQWYFUWNFED-UHFFFAOYSA-N 0.000 claims description 2
YYIIUTQRFSWRJY-UHFFFAOYSA-N n-cyclohexyl-3-methyl-5-(5-pyridin-2-ylthiophen-2-yl)-1,3,4-thiadiazol-2-imine Chemical compound CN1N=C(C=2SC(=CC=2)C=2N=CC=CC=2)SC1=NC1CCCCC1 YYIIUTQRFSWRJY-UHFFFAOYSA-N 0.000 claims description 2
PEOQETQTYREJOS-UHFFFAOYSA-N n-cyclohexyl-3-methyl-5-thiophen-3-yl-1,3,4-thiadiazol-2-imine Chemical compound CN1N=C(C2=CSC=C2)SC1=NC1CCCCC1 PEOQETQTYREJOS-UHFFFAOYSA-N 0.000 claims description 2
GSZGODOGJZULPX-UHFFFAOYSA-N n-cyclohexyl-5-(3-methoxy-4-nitrophenyl)-3-methyl-1,3,4-thiadiazol-2-imine Chemical compound C1=C([N+]([O-])=O)C(OC)=CC(C=2SC(=NC3CCCCC3)N(C)N=2)=C1 GSZGODOGJZULPX-UHFFFAOYSA-N 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
229960004889 salicylic acid Drugs 0.000 claims description 2
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 2
BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 claims 9
238000007363 ring formation reaction Methods 0.000 claims 4
OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 claims 3
IVBQQHWJIIFRAO-UHFFFAOYSA-N 3-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)phenol Chemical compound CN1N=C(C=2C=C(O)C=CC=2)SC1=NC1CCCCC1 IVBQQHWJIIFRAO-UHFFFAOYSA-N 0.000 claims 2
CSCMUJLCKQNLDE-UHFFFAOYSA-N 4-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)-n-[(3,4,5-trimethoxyphenyl)methyl]benzamide Chemical compound COC1=C(OC)C(OC)=CC(CNC(=O)C=2C=CC(=CC=2)C=2SC(=NC3CCCCC3)N(C)N=2)=C1 CSCMUJLCKQNLDE-UHFFFAOYSA-N 0.000 claims 2
ILHCAAUBKXDWAM-UHFFFAOYSA-N 4-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)benzamide Chemical compound CN1N=C(C=2C=CC(=CC=2)C(N)=O)SC1=NC1CCCCC1 ILHCAAUBKXDWAM-UHFFFAOYSA-N 0.000 claims 2
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
XWWSVPUEUSADRI-UHFFFAOYSA-N N-cyclohexyl-3-methyl-1,3,4-thiadiazol-2-imine Chemical compound C1(CCCCC1)N=C1N(N=CS1)C XWWSVPUEUSADRI-UHFFFAOYSA-N 0.000 claims 2
208000015114 central nervous system disease Diseases 0.000 claims 2
150000002431 hydrogen Chemical class 0.000 claims 2
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims 2
201000006417 multiple sclerosis Diseases 0.000 claims 2
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims 1
BOIIJURSKJYNBB-UHFFFAOYSA-N 2-[2-[[5-(4-chlorophenyl)-3-methyl-1,3,4-thiadiazol-2-ylidene]amino]phenyl]ethanol Chemical compound CN1N=C(C=2C=CC(Cl)=CC=2)SC1=NC1=CC=CC=C1CCO BOIIJURSKJYNBB-UHFFFAOYSA-N 0.000 claims 1
SIYBWQRWGWUIRN-UHFFFAOYSA-N 2-[[5-(4-chlorophenyl)-3-methyl-1,3,4-thiadiazol-2-ylidene]amino]-2-methylpropan-1-ol Chemical compound S1C(=NC(C)(C)CO)N(C)N=C1C1=CC=C(Cl)C=C1 SIYBWQRWGWUIRN-UHFFFAOYSA-N 0.000 claims 1
DNQANHIDFUSEAV-UHFFFAOYSA-N 2-[[5-(4-chlorophenyl)-3-methyl-1,3,4-thiadiazol-2-ylidene]amino]cyclohexan-1-amine Chemical compound CN1N=C(C=2C=CC(Cl)=CC=2)SC1=NC1CCCCC1N DNQANHIDFUSEAV-UHFFFAOYSA-N 0.000 claims 1
HZCCNMVBAFUWEF-UHFFFAOYSA-N 2-[[5-(4-chlorophenyl)-3-methyl-1,3,4-thiadiazol-2-ylidene]amino]phenol Chemical compound CN1N=C(C=2C=CC(Cl)=CC=2)SC1=NC1=CC=CC=C1O HZCCNMVBAFUWEF-UHFFFAOYSA-N 0.000 claims 1
LWJNSRLBFASQLU-UHFFFAOYSA-N 2-chloro-4-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)benzamide Chemical compound CN1N=C(C=2C=C(Cl)C(C(N)=O)=CC=2)SC1=NC1CCCCC1 LWJNSRLBFASQLU-UHFFFAOYSA-N 0.000 claims 1
ICVKYWHJIBOFLA-UHFFFAOYSA-N 2-chloro-5-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)-n,n-diethylbenzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N(CC)CC)=CC(C=2SC(=NC3CCCCC3)N(C)N=2)=C1 ICVKYWHJIBOFLA-UHFFFAOYSA-N 0.000 claims 1
CDJWSCIHPHMIFO-UHFFFAOYSA-N 2-chloro-5-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)-n-(2-morpholin-4-ylethyl)-n-propan-2-ylbenzenesulfonamide Chemical compound C=1C(C=2SC(=NC3CCCCC3)N(C)N=2)=CC=C(Cl)C=1S(=O)(=O)N(C(C)C)CCN1CCOCC1 CDJWSCIHPHMIFO-UHFFFAOYSA-N 0.000 claims 1
GCFAUDGLPSOEQB-UHFFFAOYSA-N 2-chloro-5-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)-n-ethyl-n-[2-(2-methoxyethoxy)ethyl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N(CCOCCOC)CC)=CC(C=2SC(=NC3CCCCC3)N(C)N=2)=C1 GCFAUDGLPSOEQB-UHFFFAOYSA-N 0.000 claims 1
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
OTGRFAYZICXAOC-UHFFFAOYSA-N 2-fluoro-5-[[3-methyl-5-(4-methylsulfonylphenyl)-1,3,4-thiadiazol-2-ylidene]amino]benzoic acid Chemical compound CN1N=C(C=2C=CC(=CC=2)S(C)(=O)=O)SC1=NC1=CC=C(F)C(C(O)=O)=C1 OTGRFAYZICXAOC-UHFFFAOYSA-N 0.000 claims 1
MKQNYQGIPARLKO-UHFFFAOYSA-N 2-methoxybenzenesulfonamide Chemical compound COC1=CC=CC=C1S(N)(=O)=O MKQNYQGIPARLKO-UHFFFAOYSA-N 0.000 claims 1
YXKICBCNUDHBDD-UHFFFAOYSA-N 3-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)-n-(2-hydroxyethyl)benzamide Chemical compound CN1N=C(C=2C=C(C=CC=2)C(=O)NCCO)SC1=NC1CCCCC1 YXKICBCNUDHBDD-UHFFFAOYSA-N 0.000 claims 1
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MRLVHNWBDMTSAS-UHFFFAOYSA-N n-cyclohexyl-3-methyl-5-(4-nitrophenyl)-1,3,4-thiadiazol-2-imine Chemical compound CN1N=C(C=2C=CC(=CC=2)[N+]([O-])=O)SC1=NC1CCCCC1 MRLVHNWBDMTSAS-UHFFFAOYSA-N 0.000 description 1
GAJHWHRFULABHR-UHFFFAOYSA-N n-cyclohexyl-3-methyl-5-phenyl-1,3,4-thiadiazol-2-imine Chemical compound CN1N=C(C=2C=CC=CC=2)SC1=NC1CCCCC1 GAJHWHRFULABHR-UHFFFAOYSA-N 0.000 description 1
GDULGJCGLRDGKU-UHFFFAOYSA-N n-cyclohexyl-5-(2,4-dichlorophenyl)-3-methyl-1,3,4-thiadiazol-2-imine Chemical compound CN1N=C(C=2C(=CC(Cl)=CC=2)Cl)SC1=NC1CCCCC1 GDULGJCGLRDGKU-UHFFFAOYSA-N 0.000 description 1
RVCRXYXXOLXFGS-UHFFFAOYSA-N n-cyclohexyl-5-[4-(1-ethyltetrazol-5-yl)phenyl]-3-methyl-1,3,4-thiadiazol-2-imine Chemical compound CCN1N=NN=C1C1=CC=C(C=2SC(=NC3CCCCC3)N(C)N=2)C=C1 RVCRXYXXOLXFGS-UHFFFAOYSA-N 0.000 description 1
SGCKSDJIMSBTFY-UHFFFAOYSA-N n-sulfonylformamide Chemical compound O=CN=S(=O)=O SGCKSDJIMSBTFY-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
101150009274 nhr-1 gene Proteins 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
230000037361 pathway Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
230000009822 protein phosphorylation Effects 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
230000004044 response Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
SWFSRMBSDMJGOK-UHFFFAOYSA-N thiadiazol-4-ol Chemical compound OC1=CSN=N1 SWFSRMBSDMJGOK-UHFFFAOYSA-N 0.000 description 1
150000003584 thiosemicarbazones Chemical class 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- 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
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Pulmonology (AREA)
Rheumatology (AREA)
Virology (AREA)
Biomedical Technology (AREA)
Physical Education & Sports Medicine (AREA)
Tropical Medicine & Parasitology (AREA)
Molecular Biology (AREA)
Endocrinology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Neurology (AREA)
Transplantation (AREA)
Diabetes (AREA)
Pain & Pain Management (AREA)
Neurosurgery (AREA)
Orthopedic Medicine & Surgery (AREA)
AIDS & HIV (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

ZA200302346A 2000-10-02 2003-03-26 New thiadiazoles and oxadiazoles and their use as phosphodiesterase-7 inhibitors. ZA200302346B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP00402710A EP1193261A1 (en)	2000-10-02	2000-10-02	New thiadiazoles and their use as phosphodiesterase-7 inhibitors

Publications (1)

Publication Number	Publication Date
ZA200302346B true ZA200302346B (en)	2004-08-04

Family

ID=8173891

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200302346A ZA200302346B (en)	2000-10-02	2003-03-26	New thiadiazoles and oxadiazoles and their use as phosphodiesterase-7 inhibitors.

Country Status (43)

Country	Link
US (1)	US7122565B2 (et)
EP (2)	EP1193261A1 (et)
JP (1)	JP4177098B2 (et)
KR (1)	KR100614158B1 (et)
CN (1)	CN1639141A (et)
AP (1)	AP1541A (et)
AR (1)	AR035347A1 (et)
AT (1)	ATE304003T1 (et)
AU (2)	AU2001289945B2 (et)
BG (1)	BG107654A (et)
BR (1)	BR0114391A (et)
CA (1)	CA2424279A1 (et)
CZ (1)	CZ2003857A3 (et)
DE (1)	DE60113283T2 (et)
DK (1)	DK1326853T3 (et)
DZ (1)	DZ3440A1 (et)
EA (1)	EA007179B1 (et)
EC (1)	ECSP034534A (et)
EE (1)	EE200300134A (et)
ES (1)	ES2247166T3 (et)
GE (1)	GEP20053459B (et)
GT (1)	GT200100196A (et)
HN (1)	HN2001000217A (et)
HR (1)	HRP20030247A2 (et)
HU (1)	HUP0301248A3 (et)
IL (1)	IL155122A0 (et)
IS (1)	IS6759A (et)
MA (1)	MA25916A1 (et)
MX (1)	MXPA03002839A (et)
NO (1)	NO20031482L (et)
NZ (1)	NZ524852A (et)
OA (1)	OA12518A (et)
PA (1)	PA8529501A1 (et)
PE (1)	PE20020419A1 (et)
PL (1)	PL366332A1 (et)
PT (1)	PT1326853E (et)
SI (1)	SI1326853T1 (et)
SK (1)	SK3812003A3 (et)
SV (1)	SV2003000633A (et)
TN (1)	TNSN01139A1 (et)
WO (1)	WO2002028847A1 (et)
YU (1)	YU24503A (et)
ZA (1)	ZA200302346B (et)

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US20150119399A1 (en)	2012-01-10	2015-04-30	President And Fellows Of Harvard College	Beta-cell replication promoting compounds and methods of their use
CN103288777A (zh) *	2013-05-28	2013-09-11	浙江禾田化工有限公司	特丁噻草隆关键中间体2-甲基氨基-5-叔丁基-1,3,4-噻二唑的合成方法
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2000
- 2000-10-02 EP EP00402710A patent/EP1193261A1/en not_active Withdrawn
2001
- 2001-09-19 SV SV2001000633A patent/SV2003000633A/es not_active Application Discontinuation
- 2001-09-26 TN TNTNSN01139A patent/TNSN01139A1/en unknown
- 2001-09-27 AR ARP010104558A patent/AR035347A1/es unknown
- 2001-09-27 PE PE2001000964A patent/PE20020419A1/es not_active Application Discontinuation
- 2001-09-27 HN HN2001000217A patent/HN2001000217A/es unknown
- 2001-09-27 PA PA20018529501A patent/PA8529501A1/es unknown
- 2001-09-27 GT GT200100196A patent/GT200100196A/es unknown
- 2001-10-01 CN CNA018182070A patent/CN1639141A/zh active Pending
- 2001-10-01 EA EA200300333A patent/EA007179B1/ru not_active IP Right Cessation
- 2001-10-01 EE EEP200300134A patent/EE200300134A/et unknown
- 2001-10-01 WO PCT/EP2001/011330 patent/WO2002028847A1/en active IP Right Grant
- 2001-10-01 SK SK381-2003A patent/SK3812003A3/sk not_active Application Discontinuation
- 2001-10-01 DK DK01969804T patent/DK1326853T3/da active
- 2001-10-01 AT AT01969804T patent/ATE304003T1/de not_active IP Right Cessation
- 2001-10-01 GE GE5120A patent/GEP20053459B/en unknown
- 2001-10-01 SI SI200130423T patent/SI1326853T1/sl unknown
- 2001-10-01 NZ NZ524852A patent/NZ524852A/en unknown
- 2001-10-01 JP JP2002532432A patent/JP4177098B2/ja not_active Expired - Fee Related
- 2001-10-01 HU HU0301248A patent/HUP0301248A3/hu unknown
- 2001-10-01 US US09/968,371 patent/US7122565B2/en not_active Expired - Fee Related
- 2001-10-01 KR KR1020037004728A patent/KR100614158B1/ko not_active IP Right Cessation
- 2001-10-01 ES ES01969804T patent/ES2247166T3/es not_active Expired - Lifetime
- 2001-10-01 MX MXPA03002839A patent/MXPA03002839A/es active IP Right Grant
- 2001-10-01 AU AU2001289945A patent/AU2001289945B2/en not_active Ceased
- 2001-10-01 CZ CZ2003857A patent/CZ2003857A3/cs unknown
- 2001-10-01 DZ DZ013440A patent/DZ3440A1/fr active
- 2001-10-01 IL IL15512201A patent/IL155122A0/xx unknown
- 2001-10-01 DE DE60113283T patent/DE60113283T2/de not_active Expired - Fee Related
- 2001-10-01 PL PL01366332A patent/PL366332A1/xx not_active Application Discontinuation
- 2001-10-01 EP EP01969804A patent/EP1326853B1/en not_active Expired - Lifetime
- 2001-10-01 BR BR0114391-3A patent/BR0114391A/pt not_active IP Right Cessation
- 2001-10-01 OA OA1200300092A patent/OA12518A/en unknown
- 2001-10-01 AU AU8994501A patent/AU8994501A/xx active Pending
- 2001-10-01 AP APAP/P/2003/002764A patent/AP1541A/en active
- 2001-10-01 PT PT01969804T patent/PT1326853E/pt unknown
- 2001-10-01 YU YU24503A patent/YU24503A/sh unknown
- 2001-10-01 CA CA002424279A patent/CA2424279A1/en not_active Abandoned
2003
- 2003-03-20 BG BG107654A patent/BG107654A/bg unknown
- 2003-03-26 ZA ZA200302346A patent/ZA200302346B/en unknown
- 2003-03-27 IS IS6759A patent/IS6759A/is unknown
- 2003-03-31 MA MA27082A patent/MA25916A1/fr unknown
- 2003-04-01 HR HR20030247A patent/HRP20030247A2/hr not_active Application Discontinuation
- 2003-04-01 EC EC2003004534A patent/ECSP034534A/es unknown
- 2003-04-01 NO NO20031482A patent/NO20031482L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2424279A1 (en)	2002-04-11
DE60113283D1 (de)	2005-10-13
AU2001289945B2 (en)	2005-12-22
NO20031482D0 (no)	2003-04-01
BG107654A (bg)	2003-12-31
TNSN01139A1 (en)	2005-11-10
GEP20053459B (en)	2005-02-25
IS6759A (is)	2003-03-27
MXPA03002839A (es)	2004-09-10
SI1326853T1 (sl)	2005-12-31
IL155122A0 (en)	2003-10-31
ECSP034534A (es)	2003-07-25
AR035347A1 (es)	2004-05-12
ATE304003T1 (de)	2005-09-15
US20030045557A1 (en)	2003-03-06
MA25916A1 (fr)	2003-10-01
EE200300134A (et)	2003-08-15
CN1639141A (zh)	2005-07-13
PT1326853E (pt)	2005-11-30
PE20020419A1 (es)	2002-07-18
HUP0301248A2 (hu)	2003-10-28
EP1326853B1 (en)	2005-09-07
PL366332A1 (en)	2005-01-24
NZ524852A (en)	2004-09-24
JP2004510769A (ja)	2004-04-08
EA200300333A1 (ru)	2003-10-30
AP2003002764A0 (en)	2003-03-31
KR100614158B1 (ko)	2006-08-21
EP1326853A1 (en)	2003-07-16
HRP20030247A2 (en)	2005-04-30
ES2247166T3 (es)	2006-03-01
PA8529501A1 (es)	2003-06-30
JP4177098B2 (ja)	2008-11-05
WO2002028847A1 (en)	2002-04-11
EP1193261A1 (en)	2002-04-03
SV2003000633A (es)	2003-04-03
HN2001000217A (es)	2002-06-13
BR0114391A (pt)	2003-06-24
US7122565B2 (en)	2006-10-17
GT200100196A (es)	2002-07-18
SK3812003A3 (en)	2004-05-04
AP1541A (en)	2006-01-11
HUP0301248A3 (en)	2005-06-28
CZ2003857A3 (cs)	2004-02-18
EA007179B1 (ru)	2006-08-25
DK1326853T3 (da)	2005-12-12
OA12518A (en)	2006-05-29
DZ3440A1 (fr)	2002-04-11
DE60113283T2 (de)	2006-06-08
KR20030068542A (ko)	2003-08-21
AU8994501A (en)	2002-04-15
YU24503A (sh)	2006-03-03
NO20031482L (no)	2003-04-01

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