ZA200204464B - Heteroaryl derivatives, their preparation and use. - Google Patents
Heteroaryl derivatives, their preparation and use. Download PDFInfo
- Publication number
- ZA200204464B ZA200204464B ZA200204464A ZA200204464A ZA200204464B ZA 200204464 B ZA200204464 B ZA 200204464B ZA 200204464 A ZA200204464 A ZA 200204464A ZA 200204464 A ZA200204464 A ZA 200204464A ZA 200204464 B ZA200204464 B ZA 200204464B
- Authority
- ZA
- South Africa
- Prior art keywords
- benzo
- piperazine
- dihydro
- dioxin
- propyl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 78
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 73
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- -1 hydroxy, formyl Chemical group 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 229960003638 dopamine Drugs 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000004442 acylamino group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 7
- OBVWOWFKXINHBA-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[3-(2-chloro-4-fluorophenyl)sulfanylpropyl]piperazine Chemical compound ClC1=CC(F)=CC=C1SCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 OBVWOWFKXINHBA-UHFFFAOYSA-N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- YHMXOOPWGYUTKI-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[4-(2-chloro-4-fluorophenoxy)butyl]piperazine Chemical compound ClC1=CC(F)=CC=C1OCCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 YHMXOOPWGYUTKI-UHFFFAOYSA-N 0.000 claims description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- AMZLAAAJJAUEIR-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[3-(2,4-difluorophenoxy)propyl]piperazine Chemical compound FC1=CC(F)=CC=C1OCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 AMZLAAAJJAUEIR-UHFFFAOYSA-N 0.000 claims description 3
- AKGXNJGARUIOBD-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[3-(4-bromo-2,6-difluorophenoxy)propyl]piperazine Chemical compound FC1=CC(Br)=CC(F)=C1OCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 AKGXNJGARUIOBD-UHFFFAOYSA-N 0.000 claims description 3
- ZZPIVMNHAACOIR-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[2-(2-ethylphenoxy)ethyl]piperazine Chemical compound CCC1=CC=CC=C1OCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 ZZPIVMNHAACOIR-UHFFFAOYSA-N 0.000 claims description 3
- OSTHWRLYUUKOFN-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[2-(2-ethylphenyl)sulfanylethyl]piperazine Chemical compound CCC1=CC=CC=C1SCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 OSTHWRLYUUKOFN-UHFFFAOYSA-N 0.000 claims description 3
- RHGFAPLUYFWFGF-UHFFFAOYSA-N 1-(5-chloro-2,2-dimethyl-3h-1-benzofuran-7-yl)-4-[4-(2-chloro-4-fluorophenoxy)butyl]piperazine Chemical compound C=12OC(C)(C)CC2=CC(Cl)=CC=1N(CC1)CCN1CCCCOC1=CC=C(F)C=C1Cl RHGFAPLUYFWFGF-UHFFFAOYSA-N 0.000 claims description 3
- ZHLYFLZPXNZYDT-UHFFFAOYSA-N 1-(5-chloro-3,3-dimethyl-2h-1-benzofuran-7-yl)-4-[4-(3-chloro-2-methoxyphenyl)sulfanylbutyl]piperazine Chemical compound COC1=C(Cl)C=CC=C1SCCCCN1CCN(C=2C3=C(C(CO3)(C)C)C=C(Cl)C=2)CC1 ZHLYFLZPXNZYDT-UHFFFAOYSA-N 0.000 claims description 3
- AWWFGCVXHYSLDZ-UHFFFAOYSA-N 1-[3-(2,6-dichloro-4-methylsulfonylphenoxy)propyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound ClC1=CC(S(=O)(=O)C)=CC(Cl)=C1OCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 AWWFGCVXHYSLDZ-UHFFFAOYSA-N 0.000 claims description 3
- QEDRYCVDNBPBEN-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)sulfanylbutyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound ClC1=CC=CC=C1SCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 QEDRYCVDNBPBEN-UHFFFAOYSA-N 0.000 claims description 3
- KAJOJUXFESGJRD-UHFFFAOYSA-N 3,5-ditert-butyl-4-[3-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]propoxy]benzonitrile Chemical compound CC(C)(C)C1=CC(C#N)=CC(C(C)(C)C)=C1OCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 KAJOJUXFESGJRD-UHFFFAOYSA-N 0.000 claims description 3
- LEFJAJIWYHTSRM-UHFFFAOYSA-N 3-chloro-4-[4-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]butoxy]benzonitrile Chemical compound ClC1=CC(C#N)=CC=C1OCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 LEFJAJIWYHTSRM-UHFFFAOYSA-N 0.000 claims description 3
- LAEYQKIDDNQLRX-UHFFFAOYSA-N 4-[3-[4-(1-benzothiophen-7-yl)piperazin-1-yl]propoxy]-3,5-dibromobenzonitrile Chemical compound BrC1=CC(C#N)=CC(Br)=C1OCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 LAEYQKIDDNQLRX-UHFFFAOYSA-N 0.000 claims description 3
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 3
- OHUJEBCVOZBFRG-UHFFFAOYSA-N 5-[4-[3-(2-chloro-4-fluorophenoxy)propyl]piperazin-1-yl]-2,3-dihydro-1,4-benzodioxine-8-carbonitrile Chemical compound ClC1=CC(F)=CC=C1OCCCN1CCN(C=2C=3OCCOC=3C(C#N)=CC=2)CC1 OHUJEBCVOZBFRG-UHFFFAOYSA-N 0.000 claims description 3
- MAWZTFGUOJAKFW-UHFFFAOYSA-N 5-[4-[3-(4-fluoro-2-methylphenoxy)propyl]piperazin-1-yl]-2,3-dihydro-1,4-benzodioxine-8-carbonitrile Chemical compound CC1=CC(F)=CC=C1OCCCN1CCN(C=2C=3OCCOC=3C(C#N)=CC=2)CC1 MAWZTFGUOJAKFW-UHFFFAOYSA-N 0.000 claims description 3
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 3
- 230000008485 antagonism Effects 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 230000002301 combined effect Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- GBMUADVJSSUAFY-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[2-(2-bromo-4,6-difluorophenoxy)ethyl]piperazine Chemical compound BrC1=CC(F)=CC(F)=C1OCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 GBMUADVJSSUAFY-UHFFFAOYSA-N 0.000 claims description 2
- DFELCASOVLBQDQ-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[3-(2,4,6-tribromophenoxy)propyl]piperazine Chemical compound BrC1=CC(Br)=CC(Br)=C1OCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 DFELCASOVLBQDQ-UHFFFAOYSA-N 0.000 claims description 2
- KBOBFWQKURVSDJ-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[3-(2,6-dibromo-4-fluorophenoxy)propyl]piperazine Chemical compound BrC1=CC(F)=CC(Br)=C1OCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 KBOBFWQKURVSDJ-UHFFFAOYSA-N 0.000 claims description 2
- AORDDQJDONDKDL-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[3-(2,6-dichloro-4-fluorophenoxy)propyl]piperazine Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 AORDDQJDONDKDL-UHFFFAOYSA-N 0.000 claims description 2
- QJSOFOBTJWCDQV-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[3-(2,6-dichlorophenyl)sulfanylpropyl]piperazine Chemical compound ClC1=CC=CC(Cl)=C1SCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 QJSOFOBTJWCDQV-UHFFFAOYSA-N 0.000 claims description 2
- FSVQGSHXUVXANA-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[4-(2,6-dichloro-4-fluorophenoxy)butyl]piperazine Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 FSVQGSHXUVXANA-UHFFFAOYSA-N 0.000 claims description 2
- VSTZDOSIKXXSAY-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[4-(2,6-dichlorophenyl)sulfanylbutyl]piperazine Chemical compound ClC1=CC=CC(Cl)=C1SCCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 VSTZDOSIKXXSAY-UHFFFAOYSA-N 0.000 claims description 2
- AXRUYOXTBAWMTK-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[4-(2-bromo-4-fluorophenoxy)butyl]piperazine Chemical compound BrC1=CC(F)=CC=C1OCCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 AXRUYOXTBAWMTK-UHFFFAOYSA-N 0.000 claims description 2
- ZPIXRTMGUPWEQR-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[4-(2-chloro-4-fluorophenyl)sulfanylbutyl]piperazine Chemical compound ClC1=CC(F)=CC=C1SCCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 ZPIXRTMGUPWEQR-UHFFFAOYSA-N 0.000 claims description 2
- KGEQHZKNEDDOHU-UHFFFAOYSA-N 1-(1-benzothiophen-7-yl)-4-[4-(3-chloro-2-methoxyphenyl)sulfanylbutyl]piperazine Chemical compound COC1=C(Cl)C=CC=C1SCCCCN1CCN(C=2C=3SC=CC=3C=CC=2)CC1 KGEQHZKNEDDOHU-UHFFFAOYSA-N 0.000 claims description 2
- HBGLLDFYLQIQSN-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[2-(2,6-dimethylphenoxy)ethyl]piperazine Chemical compound CC1=CC=CC(C)=C1OCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 HBGLLDFYLQIQSN-UHFFFAOYSA-N 0.000 claims description 2
- MJAQVVQZHTWKHY-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[2-[2-(trifluoromethyl)phenoxy]ethyl]piperazine Chemical compound FC(F)(F)C1=CC=CC=C1OCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 MJAQVVQZHTWKHY-UHFFFAOYSA-N 0.000 claims description 2
- DWLISWTXUGUKSA-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[3-(2,4,6-tribromophenoxy)propyl]piperazine Chemical compound BrC1=CC(Br)=CC(Br)=C1OCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 DWLISWTXUGUKSA-UHFFFAOYSA-N 0.000 claims description 2
- WAMBGQBREWNFTK-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[3-(2,5-dimethoxyphenyl)sulfanylpropyl]piperazine Chemical compound COC1=CC=C(OC)C(SCCCN2CCN(CC2)C=2C=3OCCOC=3C=CC=2)=C1 WAMBGQBREWNFTK-UHFFFAOYSA-N 0.000 claims description 2
- JEZPKVPXJCMFSJ-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[3-(2-ethylphenyl)sulfanylpropyl]piperazine Chemical compound CCC1=CC=CC=C1SCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 JEZPKVPXJCMFSJ-UHFFFAOYSA-N 0.000 claims description 2
- HWURCFXAVIBSTQ-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[3-(4-fluoro-2-methylphenoxy)propyl]piperazine Chemical compound CC1=CC(F)=CC=C1OCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 HWURCFXAVIBSTQ-UHFFFAOYSA-N 0.000 claims description 2
- IFLJWNXGPWDPSL-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[4-(2,6-dimethylphenyl)sulfanylbutyl]piperazine Chemical compound CC1=CC=CC(C)=C1SCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 IFLJWNXGPWDPSL-UHFFFAOYSA-N 0.000 claims description 2
- OBZNXAVXNFTMQM-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[4-(2-fluorophenyl)sulfanylbutyl]piperazine Chemical compound FC1=CC=CC=C1SCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 OBZNXAVXNFTMQM-UHFFFAOYSA-N 0.000 claims description 2
- DHKPNPGWBHWRJT-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[4-(2-methylphenyl)sulfanylbutyl]piperazine Chemical compound CC1=CC=CC=C1SCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 DHKPNPGWBHWRJT-UHFFFAOYSA-N 0.000 claims description 2
- VJJMHXLOZFIHFC-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[4-(2-propan-2-ylphenyl)sulfanylbutyl]piperazine Chemical compound CC(C)C1=CC=CC=C1SCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 VJJMHXLOZFIHFC-UHFFFAOYSA-N 0.000 claims description 2
- GWBFFBUGSGGYAP-UHFFFAOYSA-N 1-(5-chloro-2,2-dimethyl-3h-1-benzofuran-7-yl)-4-[4-(2-chloro-6-methylphenyl)sulfanylbutyl]piperazine Chemical compound CC1=CC=CC(Cl)=C1SCCCCN1CCN(C=2C=3OC(C)(C)CC=3C=C(Cl)C=2)CC1 GWBFFBUGSGGYAP-UHFFFAOYSA-N 0.000 claims description 2
- RWRDNTWWAQTGPD-UHFFFAOYSA-N 1-(5-chloro-3,3-dimethyl-2h-1-benzofuran-7-yl)-4-[3-(2,6-dichloro-4-fluorophenoxy)propyl]piperazine Chemical compound CC1(C)COC2=C1C=C(Cl)C=C2N(CC1)CCN1CCCOC1=C(Cl)C=C(F)C=C1Cl RWRDNTWWAQTGPD-UHFFFAOYSA-N 0.000 claims description 2
- BVVAJTGZGAXOTJ-UHFFFAOYSA-N 1-(5-chloro-3,3-dimethyl-2h-1-benzofuran-7-yl)-4-[3-(2-chloro-4-fluorophenyl)sulfanylpropyl]piperazine Chemical compound CC1(C)COC2=C1C=C(Cl)C=C2N(CC1)CCN1CCCSC1=CC=C(F)C=C1Cl BVVAJTGZGAXOTJ-UHFFFAOYSA-N 0.000 claims description 2
- NLQOAZOGLFWDSD-UHFFFAOYSA-N 1-(5-chloro-3,3-dimethyl-2h-1-benzofuran-7-yl)-4-[4-(2-chloro-6-methylphenyl)sulfanylbutyl]piperazine Chemical compound CC1=CC=CC(Cl)=C1SCCCCN1CCN(C=2C3=C(C(CO3)(C)C)C=C(Cl)C=2)CC1 NLQOAZOGLFWDSD-UHFFFAOYSA-N 0.000 claims description 2
- DTVCIOIMFOZPOJ-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)sulfanylethyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound ClC1=CC=CC=C1SCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 DTVCIOIMFOZPOJ-UHFFFAOYSA-N 0.000 claims description 2
- FMUWJVZASAJQLA-UHFFFAOYSA-N 1-[3-(2,3-dichlorophenyl)sulfanylpropyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound ClC1=CC=CC(SCCCN2CCN(CC2)C=2C=3OCCOC=3C=CC=2)=C1Cl FMUWJVZASAJQLA-UHFFFAOYSA-N 0.000 claims description 2
- WKYBEKKWWWMREF-UHFFFAOYSA-N 1-[3-(2,6-dichlorophenoxy)propyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound ClC1=CC=CC(Cl)=C1OCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 WKYBEKKWWWMREF-UHFFFAOYSA-N 0.000 claims description 2
- WFGOXTFQSWSXMX-UHFFFAOYSA-N 1-[3-(2-chlorophenyl)sulfanylpropyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound ClC1=CC=CC=C1SCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 WFGOXTFQSWSXMX-UHFFFAOYSA-N 0.000 claims description 2
- YYRHNTAGJQIYIF-UHFFFAOYSA-N 1-[3-(4-bromo-2,6-difluorophenoxy)propyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound FC1=CC(Br)=CC(F)=C1OCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 YYRHNTAGJQIYIF-UHFFFAOYSA-N 0.000 claims description 2
- NEKYBRDZOKSZSV-UHFFFAOYSA-N 1-[4-(2,6-dibromo-4-fluorophenoxy)butyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound BrC1=CC(F)=CC(Br)=C1OCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 NEKYBRDZOKSZSV-UHFFFAOYSA-N 0.000 claims description 2
- NJUVXCPGHKQGAO-UHFFFAOYSA-N 1-[4-(2,6-dichloro-4-fluorophenoxy)butyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 NJUVXCPGHKQGAO-UHFFFAOYSA-N 0.000 claims description 2
- DCPOLNCRGZFNPA-UHFFFAOYSA-N 1-[4-(2-bromo-4-fluorophenoxy)butyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound BrC1=CC(F)=CC=C1OCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 DCPOLNCRGZFNPA-UHFFFAOYSA-N 0.000 claims description 2
- CQDBVEOAQLYJJG-UHFFFAOYSA-N 1-[4-(4-bromo-2,6-difluorophenoxy)butyl]-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine Chemical compound FC1=CC(Br)=CC(F)=C1OCCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 CQDBVEOAQLYJJG-UHFFFAOYSA-N 0.000 claims description 2
- GPKNVYDUWLIEIM-UHFFFAOYSA-N 1-[4-[3-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]propoxy]-3,5-difluorophenyl]propan-1-one Chemical compound FC1=CC(C(=O)CC)=CC(F)=C1OCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 GPKNVYDUWLIEIM-UHFFFAOYSA-N 0.000 claims description 2
- WRKBOPMGBZERLK-UHFFFAOYSA-N 2-[3-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]propoxy]benzonitrile Chemical compound N#CC1=CC=CC=C1OCCCN1CCN(C=2C=3OCCOC=3C=CC=2)CC1 WRKBOPMGBZERLK-UHFFFAOYSA-N 0.000 claims description 2
- LIVCBWAGQRKKBY-UHFFFAOYSA-N 5-[4-[3-(2-chlorophenoxy)propyl]piperazin-1-yl]-2,3-dihydro-1,4-benzodioxine-8-carbonitrile Chemical compound ClC1=CC=CC=C1OCCCN1CCN(C=2C=3OCCOC=3C(C#N)=CC=2)CC1 LIVCBWAGQRKKBY-UHFFFAOYSA-N 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 230000008517 inhibition of serotonin uptake Effects 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
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- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
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- 125000000304 alkynyl group Chemical group 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
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- 125000002619 bicyclic group Chemical group 0.000 description 1
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- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000000950 dibromo group Chemical group Br* 0.000 description 1
- 125000004982 dihaloalkyl group Chemical group 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
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- 150000004820 halides Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
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- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- WZHJKEUHNJHDLS-QTGUNEKASA-N metergoline Chemical compound C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4N(C)C=C(C=34)C2)C1)C)NC(=O)OCC1=CC=CC=C1 WZHJKEUHNJHDLS-QTGUNEKASA-N 0.000 description 1
- 229960004650 metergoline Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
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- 230000002285 radioactive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 108010006590 serotonin 5 receptor Proteins 0.000 description 1
- 239000000387 serotonin 5-HT4 receptor agonist Substances 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 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
- ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA199901884 | 1999-12-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200204464B true ZA200204464B (en) | 2003-09-04 |
Family
ID=8108797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200204464A ZA200204464B (en) | 1999-12-30 | 2002-06-04 | Heteroaryl derivatives, their preparation and use. |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US20030050306A1 (is) |
| EP (1) | EP1246820A1 (is) |
| JP (1) | JP2003519229A (is) |
| KR (1) | KR20020063286A (is) |
| CN (1) | CN1414963A (is) |
| AR (1) | AR027133A1 (is) |
| AU (1) | AU2352001A (is) |
| BG (1) | BG106846A (is) |
| BR (1) | BR0016954A (is) |
| CA (1) | CA2395984A1 (is) |
| CZ (1) | CZ20022280A3 (is) |
| EA (1) | EA200200733A1 (is) |
| HU (1) | HUP0204084A3 (is) |
| IL (1) | IL149993A0 (is) |
| IS (1) | IS6403A (is) |
| NO (1) | NO20023188L (is) |
| NZ (1) | NZ519478A (is) |
| PL (1) | PL355610A1 (is) |
| SK (1) | SK9432002A3 (is) |
| TR (1) | TR200201679T2 (is) |
| WO (1) | WO2001049683A1 (is) |
| ZA (1) | ZA200204464B (is) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2453837C (en) * | 2001-07-20 | 2011-10-04 | Psychogenics, Inc. | Treatment for attention-deficit hyperactivity disorder using eltoprazine and related compounds |
| TWI320783B (en) | 2005-04-14 | 2010-02-21 | Otsuka Pharma Co Ltd | Heterocyclic compound |
| TWI329641B (en) * | 2005-08-31 | 2010-09-01 | Otsuka Pharma Co Ltd | (benzo[b]thiophen-4-yl)piperazine compounds, pharmaceutical compositions comprising the same, uses of the same and processes for preparing the same |
| ES2528797T3 (es) | 2006-08-21 | 2015-02-12 | Genentech, Inc. | Compuestos de aza-benzotiofenilo y métodos de uso |
| JP4785881B2 (ja) * | 2007-02-27 | 2011-10-05 | 大塚製薬株式会社 | 医薬 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK148392D0 (da) * | 1992-12-09 | 1992-12-09 | Lundbeck & Co As H | Heterocykliske forbindelser |
| IT1266582B1 (it) * | 1993-07-30 | 1997-01-09 | Recordati Chem Pharm | Derivati (di)azacicloesanici e diazacicloeptanici |
| AR022303A1 (es) * | 1999-01-22 | 2002-09-04 | Lundbeck & Co As H | Derivados de piperidina, tetrahidropiridina y piperazina, su preparacion y utilizacion |
-
2000
- 2000-12-28 AR ARP000106988A patent/AR027133A1/es not_active Application Discontinuation
- 2000-12-29 CN CN00818091A patent/CN1414963A/zh active Pending
- 2000-12-29 BR BR0016954-4A patent/BR0016954A/pt not_active IP Right Cessation
- 2000-12-29 SK SK943-2002A patent/SK9432002A3/sk unknown
- 2000-12-29 AU AU23520/01A patent/AU2352001A/en not_active Abandoned
- 2000-12-29 TR TR2002/01679T patent/TR200201679T2/xx unknown
- 2000-12-29 CA CA002395984A patent/CA2395984A1/en not_active Abandoned
- 2000-12-29 EP EP00987206A patent/EP1246820A1/en not_active Withdrawn
- 2000-12-29 EA EA200200733A patent/EA200200733A1/ru unknown
- 2000-12-29 CZ CZ20022280A patent/CZ20022280A3/cs unknown
- 2000-12-29 HU HU0204084A patent/HUP0204084A3/hu unknown
- 2000-12-29 JP JP2001550223A patent/JP2003519229A/ja not_active Withdrawn
- 2000-12-29 NZ NZ519478A patent/NZ519478A/en unknown
- 2000-12-29 IL IL14999300A patent/IL149993A0/xx unknown
- 2000-12-29 KR KR1020027008584A patent/KR20020063286A/ko not_active Application Discontinuation
- 2000-12-29 WO PCT/DK2000/000741 patent/WO2001049683A1/en not_active Application Discontinuation
- 2000-12-29 PL PL00355610A patent/PL355610A1/xx not_active Application Discontinuation
-
2002
- 2002-05-31 IS IS6403A patent/IS6403A/is unknown
- 2002-06-04 ZA ZA200204464A patent/ZA200204464B/en unknown
- 2002-06-19 BG BG106846A patent/BG106846A/xx unknown
- 2002-06-25 US US10/183,957 patent/US20030050306A1/en not_active Abandoned
- 2002-07-01 NO NO20023188A patent/NO20023188L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2352001A (en) | 2001-07-16 |
| NZ519478A (en) | 2004-02-27 |
| TR200201679T2 (tr) | 2002-10-21 |
| US20030050306A1 (en) | 2003-03-13 |
| AR027133A1 (es) | 2003-03-12 |
| BR0016954A (pt) | 2003-04-29 |
| EA200200733A1 (ru) | 2002-12-26 |
| CA2395984A1 (en) | 2001-07-12 |
| JP2003519229A (ja) | 2003-06-17 |
| IL149993A0 (en) | 2002-12-01 |
| IS6403A (is) | 2002-05-31 |
| CN1414963A (zh) | 2003-04-30 |
| HUP0204084A3 (en) | 2005-02-28 |
| HUP0204084A2 (hu) | 2003-03-28 |
| NO20023188D0 (no) | 2002-07-01 |
| PL355610A1 (en) | 2004-05-04 |
| CZ20022280A3 (cs) | 2002-10-16 |
| SK9432002A3 (en) | 2002-11-06 |
| EP1246820A1 (en) | 2002-10-09 |
| NO20023188L (no) | 2002-07-01 |
| BG106846A (en) | 2003-02-28 |
| KR20020063286A (ko) | 2002-08-01 |
| WO2001049683A1 (en) | 2001-07-12 |
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