CA2483619A1 - Novel compounds and their use - Google Patents
Novel compounds and their use Download PDFInfo
- Publication number
- CA2483619A1 CA2483619A1 CA002483619A CA2483619A CA2483619A1 CA 2483619 A1 CA2483619 A1 CA 2483619A1 CA 002483619 A CA002483619 A CA 002483619A CA 2483619 A CA2483619 A CA 2483619A CA 2483619 A1 CA2483619 A1 CA 2483619A1
- Authority
- CA
- Canada
- Prior art keywords
- pyridin
- trifluoromethyl
- piperazine
- acetate
- cndot
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 102
- 238000000034 method Methods 0.000 claims abstract description 45
- 208000008589 Obesity Diseases 0.000 claims abstract description 12
- 235000020824 obesity Nutrition 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 102
- -1 C2-6-alkyl Chemical group 0.000 claims description 77
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 46
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 claims description 35
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 208000035475 disorder Diseases 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 229940076279 serotonin Drugs 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical group 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 208000019901 Anxiety disease Diseases 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 208000030814 Eating disease Diseases 0.000 claims description 10
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 10
- 235000014632 disordered eating Nutrition 0.000 claims description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 206010046543 Urinary incontinence Diseases 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 7
- 206010015037 epilepsy Diseases 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 238000011321 prophylaxis Methods 0.000 claims description 7
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 7
- 201000009032 substance abuse Diseases 0.000 claims description 7
- 231100000736 substance abuse Toxicity 0.000 claims description 7
- 208000011117 substance-related disease Diseases 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 208000010412 Glaucoma Diseases 0.000 claims description 6
- 208000026139 Memory disease Diseases 0.000 claims description 6
- 206010027304 Menopausal symptoms Diseases 0.000 claims description 6
- 208000019022 Mood disease Diseases 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 230000000561 anti-psychotic effect Effects 0.000 claims description 6
- 208000014679 binge eating disease Diseases 0.000 claims description 6
- 238000001647 drug administration Methods 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 230000004584 weight gain Effects 0.000 claims description 6
- 235000019786 weight gain Nutrition 0.000 claims description 6
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 5
- 208000032841 Bulimia Diseases 0.000 claims description 5
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- 239000000460 chlorine Substances 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
- 230000003287 optical effect Effects 0.000 claims description 5
- 150000004885 piperazines Chemical class 0.000 claims description 5
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- XJXIZRHEURHPLD-GFCCVEGCSA-N (2r)-1-[6-[(2-chlorophenyl)methylsulfanyl]-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine Chemical compound C[C@@H]1CNCCN1C1=CC=C(C(F)(F)F)C(SCC=2C(=CC=CC=2)Cl)=N1 XJXIZRHEURHPLD-GFCCVEGCSA-N 0.000 claims description 3
- OLQYIWBVVISDKZ-SSDOTTSWSA-N (2r)-1-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine Chemical compound C[C@@H]1CNCCN1C1=CC=C(C(F)(F)F)C(Cl)=N1 OLQYIWBVVISDKZ-SSDOTTSWSA-N 0.000 claims description 3
- YAINNWCNLIVZRL-SECBINFHSA-N (2r)-1-[6-ethylsulfanyl-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine Chemical compound C1=C(C(F)(F)F)C(SCC)=NC(N2[C@@H](CNCC2)C)=C1 YAINNWCNLIVZRL-SECBINFHSA-N 0.000 claims description 3
- SZSVGTFMHBWDFK-CYBMUJFWSA-N (2r)-2-methyl-1-[6-phenylmethoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C[C@@H]1CNCCN1C1=CC=C(C(F)(F)F)C(OCC=2C=CC=CC=2)=N1 SZSVGTFMHBWDFK-CYBMUJFWSA-N 0.000 claims description 3
- NTUXZOOPCXJLMQ-SECBINFHSA-N (3r)-1-[6-ethylsulfanyl-5-(trifluoromethyl)pyridin-2-yl]-3-methylpiperazine Chemical compound C1=C(C(F)(F)F)C(SCC)=NC(N2C[C@@H](C)NCC2)=C1 NTUXZOOPCXJLMQ-SECBINFHSA-N 0.000 claims description 3
- MGNJRCXEEAHGRW-CYBMUJFWSA-N (3r)-3-methyl-1-[6-phenylmethoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1CN[C@H](C)CN1C1=CC=C(C(F)(F)F)C(OCC=2C=CC=CC=2)=N1 MGNJRCXEEAHGRW-CYBMUJFWSA-N 0.000 claims description 3
- SGLNIXKCLOPOJJ-ZETCQYMHSA-N (3s)-1-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-3-methylpiperazine Chemical compound C1CN[C@@H](C)CN1C1=CC=C(C(F)(F)F)C(Cl)=N1 SGLNIXKCLOPOJJ-ZETCQYMHSA-N 0.000 claims description 3
- JDBDRBLDOHFQGQ-UHFFFAOYSA-N 1-[6-(1-phenylethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C=1C=CC=CC=1C(C)OC(C(=CC=1)C(F)(F)F)=NC=1N1CCNCC1 JDBDRBLDOHFQGQ-UHFFFAOYSA-N 0.000 claims description 3
- BRXXSRUTEAWYSZ-UHFFFAOYSA-N 1-[6-(2-cyclohexylethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCCC1CCCCC1 BRXXSRUTEAWYSZ-UHFFFAOYSA-N 0.000 claims description 3
- ISXKGCKVAMMYCG-UHFFFAOYSA-N 1-[6-(2-cyclopentylethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCCC1CCCC1 ISXKGCKVAMMYCG-UHFFFAOYSA-N 0.000 claims description 3
- CWMFJKDGYIOIEP-UHFFFAOYSA-N 1-[6-(2-phenoxyethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCCOC1=CC=CC=C1 CWMFJKDGYIOIEP-UHFFFAOYSA-N 0.000 claims description 3
- ZTWDVAVUSQVHNU-UHFFFAOYSA-N 1-[6-(thiophen-3-ylmethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC=1C=CSC=1 ZTWDVAVUSQVHNU-UHFFFAOYSA-N 0.000 claims description 3
- KGIUCJODDPAOCP-UHFFFAOYSA-N 1-[6-[(2-chlorophenyl)methylsulfanyl]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1SCC1=CC=CC=C1Cl KGIUCJODDPAOCP-UHFFFAOYSA-N 0.000 claims description 3
- AOWTUWQUERQYNR-UHFFFAOYSA-N 1-[6-[(5-fluoro-2-methoxyphenyl)methoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound COC1=CC=C(F)C=C1COC1=NC(N2CCNCC2)=CC=C1C(F)(F)F AOWTUWQUERQYNR-UHFFFAOYSA-N 0.000 claims description 3
- LADXOCROYYAJEV-UHFFFAOYSA-N 1-[6-cyclopentyloxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OC1CCCC1 LADXOCROYYAJEV-UHFFFAOYSA-N 0.000 claims description 3
- GGIPYRBPIJCYSD-UHFFFAOYSA-N 1-[6-ethylsulfanyl-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1=C(C(F)(F)F)C(SCC)=NC(N2CCNCC2)=C1 GGIPYRBPIJCYSD-UHFFFAOYSA-N 0.000 claims description 3
- JEVYYEYMKYNXTN-UHFFFAOYSA-N 1-[6-methoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1=C(C(F)(F)F)C(OC)=NC(N2CCNCC2)=C1 JEVYYEYMKYNXTN-UHFFFAOYSA-N 0.000 claims description 3
- OCEZFJULIYXWAR-UHFFFAOYSA-N 1-[6-phenylmethoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC1=CC=CC=C1 OCEZFJULIYXWAR-UHFFFAOYSA-N 0.000 claims description 3
- VREOKOJKZOOCSM-UHFFFAOYSA-N 3-[[6-piperazin-1-yl-3-(trifluoromethyl)pyridin-2-yl]oxymethyl]benzonitrile Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC1=CC=CC(C#N)=C1 VREOKOJKZOOCSM-UHFFFAOYSA-N 0.000 claims description 3
- BMBLRVKOLIKNPO-UHFFFAOYSA-N 8-[2-[6-piperazin-1-yl-3-(trifluoromethyl)pyridin-2-yl]oxyethoxy]quinoline Chemical compound N1=C(OCCOC=2C3=NC=CC=C3C=CC=2)C(C(F)(F)F)=CC=C1N1CCNCC1 BMBLRVKOLIKNPO-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 150000001450 anions Chemical class 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
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000000651 prodrug Chemical group 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- XJXIZRHEURHPLD-LBPRGKRZSA-N (2s)-1-[6-[(2-chlorophenyl)methylsulfanyl]-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine Chemical compound C[C@H]1CNCCN1C1=CC=C(C(F)(F)F)C(SCC=2C(=CC=CC=2)Cl)=N1 XJXIZRHEURHPLD-LBPRGKRZSA-N 0.000 claims description 2
- OLQYIWBVVISDKZ-ZETCQYMHSA-N (2s)-1-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine Chemical compound C[C@H]1CNCCN1C1=CC=C(C(F)(F)F)C(Cl)=N1 OLQYIWBVVISDKZ-ZETCQYMHSA-N 0.000 claims description 2
- SZSVGTFMHBWDFK-ZDUSSCGKSA-N (2s)-2-methyl-1-[6-phenylmethoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C[C@H]1CNCCN1C1=CC=C(C(F)(F)F)C(OCC=2C=CC=CC=2)=N1 SZSVGTFMHBWDFK-ZDUSSCGKSA-N 0.000 claims description 2
- SGLNIXKCLOPOJJ-SSDOTTSWSA-N (3r)-1-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-3-methylpiperazine Chemical compound C1CN[C@H](C)CN1C1=CC=C(C(F)(F)F)C(Cl)=N1 SGLNIXKCLOPOJJ-SSDOTTSWSA-N 0.000 claims description 2
- NWBUKSZRBSOPDH-LBPRGKRZSA-N (3s)-1-[6-[(2-chlorophenyl)methylsulfanyl]-5-(trifluoromethyl)pyridin-2-yl]-3-methylpiperazine Chemical compound C1CN[C@@H](C)CN1C1=CC=C(C(F)(F)F)C(SCC=2C(=CC=CC=2)Cl)=N1 NWBUKSZRBSOPDH-LBPRGKRZSA-N 0.000 claims description 2
- NTUXZOOPCXJLMQ-VIFPVBQESA-N (3s)-1-[6-ethylsulfanyl-5-(trifluoromethyl)pyridin-2-yl]-3-methylpiperazine Chemical compound C1=C(C(F)(F)F)C(SCC)=NC(N2C[C@H](C)NCC2)=C1 NTUXZOOPCXJLMQ-VIFPVBQESA-N 0.000 claims description 2
- MGNJRCXEEAHGRW-ZDUSSCGKSA-N (3s)-3-methyl-1-[6-phenylmethoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1CN[C@@H](C)CN1C1=CC=C(C(F)(F)F)C(OCC=2C=CC=CC=2)=N1 MGNJRCXEEAHGRW-ZDUSSCGKSA-N 0.000 claims description 2
- PNJPYOVAPXMJKI-UHFFFAOYSA-N 1-[6-(2,3-dihydro-1,4-benzodioxin-6-ylmethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound N1=C(OCC=2C=C3OCCOC3=CC=2)C(C(F)(F)F)=CC=C1N1CCNCC1 PNJPYOVAPXMJKI-UHFFFAOYSA-N 0.000 claims description 2
- LGUCZURKPZRUKT-UHFFFAOYSA-N 1-[6-(2-naphthalen-2-yloxyethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound N1=C(OCCOC=2C=C3C=CC=CC3=CC=2)C(C(F)(F)F)=CC=C1N1CCNCC1 LGUCZURKPZRUKT-UHFFFAOYSA-N 0.000 claims description 2
- GJZATGDNYDSWNH-UHFFFAOYSA-N 1-[6-(3-pyridin-3-ylpropoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCCCC1=CC=CN=C1 GJZATGDNYDSWNH-UHFFFAOYSA-N 0.000 claims description 2
- GGMIYHLTSHVBCU-UHFFFAOYSA-N 1-[6-(furan-2-ylmethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC1=CC=CO1 GGMIYHLTSHVBCU-UHFFFAOYSA-N 0.000 claims description 2
- IEFCYRREPDRTBO-UHFFFAOYSA-N 1-[6-[(2,6-difluorophenyl)methoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC1=CC=CC(F)=C1COC1=NC(N2CCNCC2)=CC=C1C(F)(F)F IEFCYRREPDRTBO-UHFFFAOYSA-N 0.000 claims description 2
- ZZSYJFBTCLSEEN-UHFFFAOYSA-N 1-[6-[(3-methylphenyl)methylsulfanyl]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound CC1=CC=CC(CSC=2C(=CC=C(N=2)N2CCNCC2)C(F)(F)F)=C1 ZZSYJFBTCLSEEN-UHFFFAOYSA-N 0.000 claims description 2
- VLTFROJFPRTUBA-UHFFFAOYSA-N 1-[6-[[2-(phenoxymethyl)phenyl]methoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC1=CC=CC=C1COC1=CC=CC=C1 VLTFROJFPRTUBA-UHFFFAOYSA-N 0.000 claims description 2
- VRGJESCGGWQCRP-UHFFFAOYSA-N 1-[6-propoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1=C(C(F)(F)F)C(OCCC)=NC(N2CCNCC2)=C1 VRGJESCGGWQCRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000006508 2,6-difluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C(F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000003564 m-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(C#N)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 5
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000000204 (C2-C4) acyl group Chemical group 0.000 claims 1
- OBLMRDRFYUMUQH-UHFFFAOYSA-N 1-[6-[2-(2,6-difluorophenoxy)ethoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC1=CC=CC(F)=C1OCCOC1=NC(N2CCNCC2)=CC=C1C(F)(F)F OBLMRDRFYUMUQH-UHFFFAOYSA-N 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- 150000001204 N-oxides Chemical group 0.000 claims 1
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 13
- 230000008569 process Effects 0.000 abstract description 5
- 210000003169 central nervous system Anatomy 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 44
- 239000007858 starting material Substances 0.000 description 38
- 239000000203 mixture Substances 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 10
- 239000000018 receptor agonist Substances 0.000 description 10
- 229940044601 receptor agonist Drugs 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
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- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- BYTQATKOGQATMN-JTQLQIEISA-N tert-butyl (2s)-4-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)[C@@H](C)CN1C1=CC=C(C(F)(F)F)C(Cl)=N1 BYTQATKOGQATMN-JTQLQIEISA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
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- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/12—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 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Gynecology & Obstetrics (AREA)
- Pain & Pain Management (AREA)
- Nutrition Science (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Liquid Crystal Substances (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0201544A SE0201544D0 (sv) | 2002-05-17 | 2002-05-17 | Novel compounds and thier use |
| SE0201544-4 | 2002-05-17 | ||
| US41003802P | 2002-09-12 | 2002-09-12 | |
| US60/410,038 | 2002-09-12 | ||
| PCT/SE2003/000795 WO2003097636A1 (en) | 2002-05-17 | 2003-05-16 | Novel compounds and their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2483619A1 true CA2483619A1 (en) | 2003-11-27 |
Family
ID=29552452
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002483619A Abandoned CA2483619A1 (en) | 2002-05-17 | 2003-05-16 | Novel compounds and their use |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US7229997B2 (enExample) |
| EP (1) | EP1506185B1 (enExample) |
| JP (1) | JP4865221B2 (enExample) |
| KR (1) | KR20050026702A (enExample) |
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| AT (1) | ATE327229T1 (enExample) |
| AU (1) | AU2003228196B2 (enExample) |
| BR (1) | BR0310077A (enExample) |
| CA (1) | CA2483619A1 (enExample) |
| CY (1) | CY1105162T1 (enExample) |
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| DK (1) | DK1506185T3 (enExample) |
| EA (1) | EA007543B1 (enExample) |
| ES (1) | ES2263971T3 (enExample) |
| IL (1) | IL164974A0 (enExample) |
| MX (1) | MXPA04011437A (enExample) |
| NO (1) | NO20045486L (enExample) |
| NZ (1) | NZ536409A (enExample) |
| PT (1) | PT1506185E (enExample) |
| RS (1) | RS99804A (enExample) |
| SE (1) | SE0201544D0 (enExample) |
| SI (1) | SI1506185T1 (enExample) |
| WO (1) | WO2003097636A1 (enExample) |
| ZA (1) | ZA200408975B (enExample) |
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| US20030236259A1 (en) * | 2002-02-05 | 2003-12-25 | Rolf Hohlweg | Novel aryl- and heteroarylpiperazines |
| WO2006022420A1 (ja) * | 2004-08-25 | 2006-03-02 | Takeda Pharmaceutical Company Limited | 腹圧性尿失禁の予防・治療剤及びそのスクリーニング方法 |
| GT200500317A (es) * | 2004-11-05 | 2006-10-27 | Proceso para preparar compuestos de quinolina y productos obtenidos de los mismos | |
| KR101286569B1 (ko) | 2005-07-04 | 2013-07-23 | 하이 포인트 파마슈티칼스, 엘엘씨 | 신규 약제 |
| AR054849A1 (es) * | 2005-07-26 | 2007-07-18 | Wyeth Corp | Diazepinoquinolinas, sintesis de las mismas, e intermediarios para obtenerlas |
| JO2769B1 (en) | 2005-10-26 | 2014-03-15 | جانسين فارماسوتيكا ان. في | Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor |
| TW200734334A (en) * | 2006-01-13 | 2007-09-16 | Wyeth Corp | Treatment of substance abuse |
| US20070225279A1 (en) * | 2006-03-24 | 2007-09-27 | Wyeth | Therapeutic combinations for the treatment of depression |
| PE20081192A1 (es) * | 2006-03-24 | 2008-10-07 | Wyeth Corp | Tratamiento del dolor |
| JP5528699B2 (ja) | 2006-05-16 | 2014-06-25 | 武田薬品工業株式会社 | 縮合複素環化合物およびその用途 |
| DK2079732T3 (da) * | 2006-05-29 | 2012-01-23 | High Point Pharmaceuticals Llc | 3-(1,3-benzodioxol-5-yl)-6-(4-cyclopropylpiperazin-1-yl)-pyridazin, dets salte og solvater og dets anvendelse som histamin H3-receptorantagonister |
| US20070293475A1 (en) * | 2006-06-20 | 2007-12-20 | Alcon Manufacturing Ltd. | Aryl and heteroaryl tetrahydrobenzazepine derivatives and their use for treating glaucoma |
| AR063373A1 (es) * | 2006-10-24 | 2009-01-21 | Wyeth Corp | Derivados de benzodioxano y sus usos |
| JO2642B1 (en) | 2006-12-08 | 2012-06-17 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| JO2849B1 (en) | 2007-02-13 | 2015-03-15 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| SI2148873T1 (sl) | 2007-04-23 | 2013-01-31 | Janssen Pharmaceutica, N.V. | Derivati 4-alkoksipiridazina kot antagonisti receptorja dopamina 2 s hitro disociacijo |
| ES2400710T3 (es) | 2007-04-23 | 2013-04-11 | Janssen Pharmaceutica, N.V. | Tia(dia)zoles como antagonistas del receptor de dopamina 2 de disociación rápida |
| EP2014656A3 (en) * | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| CL2008002777A1 (es) * | 2007-09-21 | 2010-01-22 | Wyeth Corp | Metodo de preparacion de compuestos diazepinoquinolinicos quirales por recristalizacion en un sistema de solvente ternario. |
| JP5520051B2 (ja) | 2007-11-15 | 2014-06-11 | 武田薬品工業株式会社 | 縮合ピリジン誘導体およびその用途 |
| ES2398625T3 (es) | 2008-07-03 | 2013-03-20 | Janssen Pharmaceutica N.V. | 6-(1-Piperazinil)-piritazinas sustituidas como antagonistas de receptores 5-HT6 |
| US8895562B2 (en) | 2008-07-31 | 2014-11-25 | Janssen Pharmaceutica Nv | Piperazin-1-yl-trifluoromethyl-substituted-pyridines as fast dissociating dopamine 2 receptor antagonists |
| AR077094A1 (es) | 2009-06-15 | 2011-08-03 | Takeda Pharmaceutical | Derivados de pirazinooxazepina, composiciones farmaceuticas y su uso en el tratamiento de un sintoma del aparato urinario inferior, obesidad y/o prolapso de organos |
| EP2510949A4 (en) | 2009-12-11 | 2013-11-13 | Astellas Pharma Inc | THERAPEUTICS FOR FIBROMYALGIA |
| US20130267500A1 (en) | 2010-09-01 | 2013-10-10 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists in the treatment of disorders ameliorated by reduction of norepinephrine level |
| WO2013010679A1 (en) | 2011-07-15 | 2013-01-24 | Novartis Ag | Salts of aza-bicyclic di-aryl ethers and methods to make them or their precursors |
| WO2015066344A1 (en) | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists and compositions and methods of use |
| EP3733204A4 (en) | 2017-12-27 | 2021-09-15 | Takeda Pharmaceutical Company Limited | THERAPEUTIC AGENT FOR URINARY INCONTINENCE OF STRESS AND FECAL INCONTINENCE |
| TW202504600A (zh) * | 2023-07-04 | 2025-02-01 | 大陸商杭州中美華東製藥有限公司 | Glp1r激動劑及其中間體的製備方法 |
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| US4078063A (en) * | 1976-09-24 | 1978-03-07 | Merck & Co., Inc. | Piperazinylpyridines |
| EP0370560B1 (en) * | 1988-11-24 | 1994-01-12 | Akzo Nobel N.V. | Pharmaceutical composition containing 1-[mono- or bis (trifluoromethyl)-2-pyridinyl] piperazines |
| EP0580465A1 (fr) * | 1992-06-25 | 1994-01-26 | Sanofi | Nouvelle utilisation thérapeutique d'hétérocyclyl-pipérazines comme 5-HT3 agonistes et nouveaux dérivés |
| JPH0665203A (ja) * | 1992-06-25 | 1994-03-08 | Elf Sanofi | ピペラジンのヘテロ環誘導体 |
| SE9202265D0 (sv) * | 1992-07-31 | 1992-07-31 | Kabi Pharmacia Ab | Novel- pyridyl and pyrimidylpiperazine derivatives |
| JPH0797370A (ja) * | 1993-09-29 | 1995-04-11 | Asahi Chem Ind Co Ltd | 2−アルコキシピラジン誘導体およびその用途 |
| WO1998033504A1 (en) * | 1997-02-03 | 1998-08-06 | Akzo Nobel N.V. | Treatment of urinary incontinence |
| JP3989102B2 (ja) * | 1997-10-02 | 2007-10-10 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 縮合ピリジン誘導体 |
| UA77650C2 (en) * | 1999-12-06 | 2007-01-15 | Lundbeck & Co As H | Use of serotonin reuptake inhibitor in combination with deramcyclane |
| KR100846339B1 (ko) * | 2000-11-20 | 2008-07-15 | 바이오비트럼 에이비(피유비엘) | 세로토닌 5ht-2 수용체의 아고니스트 또는안타고니스트로서의 피페라지닐피라진 화합물 |
| US6498184B2 (en) * | 2000-12-05 | 2002-12-24 | Akzo Nobel N.V. | Serotonergic compound for a method of treatment of hot flushes in post-menopausal women |
| EP1213017A3 (en) * | 2000-12-05 | 2003-11-12 | Akzo Nobel N.V. | Use of a 5-HT2C receptor agonist for the treatment of hot flushes |
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2003
- 2003-05-16 NZ NZ536409A patent/NZ536409A/en unknown
- 2003-05-16 JP JP2004505369A patent/JP4865221B2/ja not_active Expired - Fee Related
- 2003-05-16 DE DE60305484T patent/DE60305484T2/de not_active Expired - Lifetime
- 2003-05-16 KR KR1020047018539A patent/KR20050026702A/ko not_active Ceased
- 2003-05-16 PT PT03725958T patent/PT1506185E/pt unknown
- 2003-05-16 EP EP03725958A patent/EP1506185B1/en not_active Expired - Lifetime
- 2003-05-16 ES ES03725958T patent/ES2263971T3/es not_active Expired - Lifetime
- 2003-05-16 MX MXPA04011437A patent/MXPA04011437A/es active IP Right Grant
- 2003-05-16 BR BR0310077-4A patent/BR0310077A/pt not_active IP Right Cessation
- 2003-05-16 AT AT03725958T patent/ATE327229T1/de not_active IP Right Cessation
- 2003-05-16 ZA ZA200408975A patent/ZA200408975B/en unknown
- 2003-05-16 RS YU99804A patent/RS99804A/sr unknown
- 2003-05-16 US US10/440,011 patent/US7229997B2/en not_active Expired - Fee Related
- 2003-05-16 DK DK03725958T patent/DK1506185T3/da active
- 2003-05-16 EA EA200401526A patent/EA007543B1/ru not_active IP Right Cessation
- 2003-05-16 CN CNB038112493A patent/CN1329389C/zh not_active Expired - Fee Related
- 2003-05-16 AU AU2003228196A patent/AU2003228196B2/en not_active Expired - Fee Related
- 2003-05-16 WO PCT/SE2003/000795 patent/WO2003097636A1/en not_active Ceased
- 2003-05-16 SI SI200330377T patent/SI1506185T1/sl unknown
- 2003-05-16 CA CA002483619A patent/CA2483619A1/en not_active Abandoned
-
2004
- 2004-11-01 IL IL16497404A patent/IL164974A0/xx unknown
- 2004-12-16 NO NO20045486A patent/NO20045486L/no not_active Application Discontinuation
-
2006
- 2006-08-23 CY CY20061101170T patent/CY1105162T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1506185B1 (en) | 2006-05-24 |
| EP1506185A1 (en) | 2005-02-16 |
| DE60305484T2 (de) | 2006-11-09 |
| WO2003097636A1 (en) | 2003-11-27 |
| JP2005529926A (ja) | 2005-10-06 |
| CN1701068A (zh) | 2005-11-23 |
| KR20050026702A (ko) | 2005-03-15 |
| EA200401526A1 (ru) | 2005-04-28 |
| ES2263971T3 (es) | 2006-12-16 |
| US20030232814A1 (en) | 2003-12-18 |
| SE0201544D0 (sv) | 2002-05-17 |
| CY1105162T1 (el) | 2010-03-03 |
| HK1084941A1 (en) | 2006-08-11 |
| DE60305484D1 (de) | 2006-06-29 |
| NZ536409A (en) | 2007-11-30 |
| PT1506185E (pt) | 2006-10-31 |
| CN1329389C (zh) | 2007-08-01 |
| ATE327229T1 (de) | 2006-06-15 |
| IL164974A0 (en) | 2005-12-18 |
| SI1506185T1 (sl) | 2006-10-31 |
| US7229997B2 (en) | 2007-06-12 |
| AU2003228196A1 (en) | 2003-12-02 |
| MXPA04011437A (es) | 2005-02-17 |
| ZA200408975B (en) | 2005-11-14 |
| DK1506185T3 (da) | 2006-10-02 |
| NO20045486L (no) | 2005-02-02 |
| EA007543B1 (ru) | 2006-10-27 |
| RS99804A (sr) | 2006-12-15 |
| AU2003228196B2 (en) | 2009-12-17 |
| BR0310077A (pt) | 2005-02-22 |
| JP4865221B2 (ja) | 2012-02-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |