ES2242028T3 - Derivados de pirazolo(1,5-a)piridina. - Google Patents
Derivados de pirazolo(1,5-a)piridina.Info
- Publication number
- ES2242028T3 ES2242028T3 ES02733945T ES02733945T ES2242028T3 ES 2242028 T3 ES2242028 T3 ES 2242028T3 ES 02733945 T ES02733945 T ES 02733945T ES 02733945 T ES02733945 T ES 02733945T ES 2242028 T3 ES2242028 T3 ES 2242028T3
- Authority
- ES
- Spain
- Prior art keywords
- het
- formula
- compound
- pyrazolo
- pyridin
- 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.)
- Expired - Lifetime
Links
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 615
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 138
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 123
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 78
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 63
- 125000003118 aryl group Chemical group 0.000 claims abstract description 43
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 239000012453 solvate Substances 0.000 claims abstract description 27
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 26
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 154
- 238000000034 method Methods 0.000 claims description 117
- 125000005843 halogen group Chemical group 0.000 claims description 107
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 76
- 125000000623 heterocyclic group Chemical group 0.000 claims description 61
- 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 56
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 55
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 49
- 238000011282 treatment Methods 0.000 claims description 46
- 125000004429 atom Chemical group 0.000 claims description 41
- 238000011321 prophylaxis Methods 0.000 claims description 33
- 150000001412 amines Chemical class 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 31
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 29
- 241001465754 Metazoa Species 0.000 claims description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 230000000269 nucleophilic effect Effects 0.000 claims description 21
- 230000003612 virological effect Effects 0.000 claims description 21
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 150000004820 halides Chemical class 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 15
- 208000015181 infectious disease Diseases 0.000 claims description 15
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 14
- 206010019973 Herpes virus infection Diseases 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 13
- 230000002140 halogenating effect Effects 0.000 claims description 13
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 101100079984 Caenorhabditis elegans nhr-9 gene Proteins 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 229910052751 metal Inorganic materials 0.000 claims description 11
- 239000002184 metal Substances 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 claims description 8
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- TXBSMCXEGQSASW-UHFFFAOYSA-N 7-(cyclopentylamino)-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C=1C=CC2=C(C=3N=C(NC4CCCC4)N=CC=3)C(C=3C=CC(F)=CC=3)=NN2C=1NC1CCCC1 TXBSMCXEGQSASW-UHFFFAOYSA-N 0.000 claims description 7
- 229960004150 aciclovir Drugs 0.000 claims description 7
- UPURSWNGJDCEHG-UHFFFAOYSA-N n-cyclopentyl-4-[5,7-dichloro-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1C1=NN(C(Cl)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 UPURSWNGJDCEHG-UHFFFAOYSA-N 0.000 claims description 7
- 229940093257 valacyclovir Drugs 0.000 claims description 7
- CZTZEVVZGFJDAQ-UHFFFAOYSA-N 5,7-dichloro-2-(4-methoxyphenyl)-3-(2-methylsulfanylpyrimidin-4-yl)pyrazolo[1,5-a]pyridine Chemical compound C1=CC(OC)=CC=C1C1=NN(C(Cl)=CC(Cl)=C2)C2=C1C1=CC=NC(SC)=N1 CZTZEVVZGFJDAQ-UHFFFAOYSA-N 0.000 claims description 6
- ARFXCYCTFNKRNL-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(OC)=CC=C1C1=NN(C(NC2CCCC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 ARFXCYCTFNKRNL-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 239000003443 antiviral agent Substances 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 6
- FQXIKSUQXMFWEC-UHFFFAOYSA-N 4-[5-chloro-7-(cyclopentylamino)-3-[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-2-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=NN(C(NC2CCCC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 FQXIKSUQXMFWEC-UHFFFAOYSA-N 0.000 claims description 5
- UHYVQIPHBDYTBN-UHFFFAOYSA-N 5-chloro-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n-propan-2-ylpyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NC(C)C)=CC(Cl)=CC2=C(C=2N=C(NC3CCCC3)N=CC=2)C=1C1=CC=C(F)C=C1 UHYVQIPHBDYTBN-UHFFFAOYSA-N 0.000 claims description 5
- WCKXXYWOSVAGLZ-UHFFFAOYSA-N 5-chloro-3-[2-(cyclopentylamino)pyrimidin-4-yl]-n-cyclopropyl-2-[4-(cyclopropylmethoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N12N=C(C=3C=CC(OCC4CC4)=CC=3)C(C=3N=C(NC4CCCC4)N=CC=3)=C2C=C(Cl)C=C1NC1CC1 WCKXXYWOSVAGLZ-UHFFFAOYSA-N 0.000 claims description 5
- GLKWTXUVFUJIGX-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-2-(4-methoxyphenyl)-3-(2-methylsulfanylpyrimidin-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(OC)=CC=C1C1=NN(C(NC2CCCC2)=CC(Cl)=C2)C2=C1C1=CC=NC(SC)=N1 GLKWTXUVFUJIGX-UHFFFAOYSA-N 0.000 claims description 5
- UZPCZQJBVPVOLG-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-[4-(cyclopropylmethoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N12N=C(C=3C=CC(OCC4CC4)=CC=3)C(C=3N=C(NC4CCCC4)N=CC=3)=C2C=C(Cl)C=C1NC1CCCC1 UZPCZQJBVPVOLG-UHFFFAOYSA-N 0.000 claims description 5
- RWOYMYIYXMICCH-UHFFFAOYSA-N 7-chloro-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC(NC2CCCC2)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 RWOYMYIYXMICCH-UHFFFAOYSA-N 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- ZKYXVDDZBFULBP-UHFFFAOYSA-N n-cyclopentyl-4-[5,7-dichloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 ZKYXVDDZBFULBP-UHFFFAOYSA-N 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- RJAIATRJLAYBKS-UHFFFAOYSA-N 4-[5-chloro-3-[2-(cyclopentylamino)pyrimidin-4-yl]-7-(cyclopropylamino)pyrazolo[1,5-a]pyridin-2-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=NN(C(NC2CC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 RJAIATRJLAYBKS-UHFFFAOYSA-N 0.000 claims description 4
- WDQYMKZMKUPSGD-UHFFFAOYSA-N 5-chloro-3-[2-(cyclopentylamino)pyrimidin-4-yl]-n-cyclopropyl-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CC1=CC=CC(C=2C(=C3C=C(Cl)C=C(NC4CC4)N3N=2)C=2N=C(NC3CCCC3)N=CC=2)=C1 WDQYMKZMKUPSGD-UHFFFAOYSA-N 0.000 claims description 4
- KUFDEHIBMUXODJ-UHFFFAOYSA-N 5-chloro-3-[2-(cyclopentylamino)pyrimidin-4-yl]-n-cyclopropyl-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 KUFDEHIBMUXODJ-UHFFFAOYSA-N 0.000 claims description 4
- CNMBLWDXHYWTLA-UHFFFAOYSA-N 5-chloro-3-[2-(cyclopentylamino)pyrimidin-4-yl]-n-cyclopropyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(OC)=CC=C1C1=NN(C(NC2CC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 CNMBLWDXHYWTLA-UHFFFAOYSA-N 0.000 claims description 4
- FERZWOQFLPMGHJ-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CC1=CC=CC(C=2C(=C3C=C(Cl)C=C(NC4CCCC4)N3N=2)C=2N=C(NC3CCCC3)N=CC=2)=C1 FERZWOQFLPMGHJ-UHFFFAOYSA-N 0.000 claims description 4
- FVDIJBUKMLLPCL-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 FVDIJBUKMLLPCL-UHFFFAOYSA-N 0.000 claims description 4
- VFJBIABMTATMLU-UHFFFAOYSA-N 6-chloro-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=C(Cl)C=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 VFJBIABMTATMLU-UHFFFAOYSA-N 0.000 claims description 4
- UMYIVFMLIMKLIJ-UHFFFAOYSA-N 7-(cyclopentylamino)-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n,n-dimethylpyrazolo[1,5-a]pyridine-6-carboxamide Chemical compound CN(C)C(=O)C=1C=CC2=C(C=3N=C(NC4CCCC4)N=CC=3)C(C=3C=CC(F)=CC=3)=NN2C=1NC1CCCC1 UMYIVFMLIMKLIJ-UHFFFAOYSA-N 0.000 claims description 4
- FQNJTEQMAQMIMU-UHFFFAOYSA-N [7-(cyclopentylamino)-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-6-yl]methanol Chemical compound OCC=1C=CC2=C(C=3N=C(NC4CCCC4)N=CC=3)C(C=3C=CC(F)=CC=3)=NN2C=1NC1CCCC1 FQNJTEQMAQMIMU-UHFFFAOYSA-N 0.000 claims description 4
- OJDKXSZDDHEORF-UHFFFAOYSA-N n-cyclopentyl-2-(4-fluorophenyl)-3-(2-pyrrolidin-1-ylpyrimidin-4-yl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=C(C=C2)C(F)(F)F)C2=C1C1=CC=NC(N2CCCC2)=N1 OJDKXSZDDHEORF-UHFFFAOYSA-N 0.000 claims description 4
- BJNRYAGMRQMAFL-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-5-(2-methoxyethoxy)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N12N=C(C=3C=CC(F)=CC=3)C(C=3N=C(NC4CCCC4)N=CC=3)=C2C=C(OCCOC)C=C1NC1CCCC1 BJNRYAGMRQMAFL-UHFFFAOYSA-N 0.000 claims description 4
- PXFIELOSJDWIRS-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-5-methoxypyrazolo[1,5-a]pyridin-7-amine Chemical compound N12N=C(C=3C=CC(F)=CC=3)C(C=3N=C(NC4CCCC4)N=CC=3)=C2C=C(OC)C=C1NC1CCCC1 PXFIELOSJDWIRS-UHFFFAOYSA-N 0.000 claims description 4
- AYUKDIIWYYVGRE-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=C(C=C2)C(F)(F)F)C2=C1C1=CC=NC(NC2CCCC2)=N1 AYUKDIIWYYVGRE-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- HCYHYJMKVPUUIL-UHFFFAOYSA-N 4,6-dibromo-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=C(Br)C=C2Br)C2=C1C1=CC=NC(NC2CCCC2)=N1 HCYHYJMKVPUUIL-UHFFFAOYSA-N 0.000 claims description 3
- CHYRWZMJWVIPTQ-UHFFFAOYSA-N 4-[5-chloro-2-(4-fluorophenyl)-7-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C1=CC(Cl)=CC2=C(C=3N=C(NC4CCCC4)N=CC=3)C(C=3C=CC(F)=CC=3)=NN12 CHYRWZMJWVIPTQ-UHFFFAOYSA-N 0.000 claims description 3
- LNAVWIDITNBXLK-UHFFFAOYSA-N 4-[5-chloro-7-(cyclopentylamino)-3-[2-(cyclopropylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-2-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=NN(C(NC2CCCC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CC2)=N1 LNAVWIDITNBXLK-UHFFFAOYSA-N 0.000 claims description 3
- YBWFABCNMJWEBO-UHFFFAOYSA-N 5-chloro-2-(3-chlorophenyl)-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound ClC1=CC=CC(C=2C(=C3C=C(Cl)C=C(NC4CCCC4)N3N=2)C=2N=C(NC3CCCC3)N=CC=2)=C1 YBWFABCNMJWEBO-UHFFFAOYSA-N 0.000 claims description 3
- KVWGXHFUCADPDK-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(OC)=CC=C1C1=NN(C(NC2CCCC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CC2)=N1 KVWGXHFUCADPDK-UHFFFAOYSA-N 0.000 claims description 3
- NVCMHZBGADACGL-UHFFFAOYSA-N 7-N,6-di(propan-2-yl)pyrazolo[1,5-a]pyridine-5,7-diamine Chemical compound CC(C)NC1=C(C(C)C)C(N)=CC2=CC=NN12 NVCMHZBGADACGL-UHFFFAOYSA-N 0.000 claims description 3
- NJOGPEWHCAYMMN-UHFFFAOYSA-N 7-N,6-dicyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-5,7-diamine Chemical compound C1CCCC1C=1C(N)=CC2=C(C=3N=C(NC4CCCC4)N=CC=3)C(C=3C=CC(F)=CC=3)=NN2C=1NC1CCCC1 NJOGPEWHCAYMMN-UHFFFAOYSA-N 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- OUTDXFTZQARBBK-UHFFFAOYSA-N n-cyclopentyl-4-[5,7-dichloro-2-(3-chlorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound ClC1=CC=CC(C=2C(=C3C=C(Cl)C=C(Cl)N3N=2)C=2N=C(NC3CCCC3)N=CC=2)=C1 OUTDXFTZQARBBK-UHFFFAOYSA-N 0.000 claims description 3
- KRBLXMLDGJHOIF-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CC1=CC=CC(C=2C(=C3C=C(Cl)C=C(NC4CCCC4)N3N=2)C=2N=C(NC3CC3)N=CC=2)=C1 KRBLXMLDGJHOIF-UHFFFAOYSA-N 0.000 claims description 2
- YPOWBVZTLGEDEB-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]-2-[4-(cyclopropylmethoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N12N=C(C=3C=CC(OCC4CC4)=CC=3)C(C=3N=C(NC4CC4)N=CC=3)=C2C=C(Cl)C=C1NC1CCCC1 YPOWBVZTLGEDEB-UHFFFAOYSA-N 0.000 claims description 2
- OLZFTPZWOUUVAX-UHFFFAOYSA-N 5-chloro-n-cyclopropyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CC2)=CC(Cl)=C2)C2=C1C1=CC=NC(NC2CC2)=N1 OLZFTPZWOUUVAX-UHFFFAOYSA-N 0.000 claims description 2
- CRJAQHLKMAMDIH-UHFFFAOYSA-N [7-(cyclopentylamino)-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-6-yl]-pyrrolidin-1-ylmethanone Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=C(C=C2)C(=O)N3CCCC3)C2=C1C1=CC=NC(NC2CCCC2)=N1 CRJAQHLKMAMDIH-UHFFFAOYSA-N 0.000 claims description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 2
- 241000175212 Herpesvirales Species 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 abstract description 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 abstract description 6
- 125000001475 halogen functional group Chemical group 0.000 abstract 3
- 102200160920 rs35304565 Human genes 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- 239000000203 mixture Substances 0.000 description 82
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- 239000007787 solid Substances 0.000 description 77
- 239000000243 solution Substances 0.000 description 76
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 74
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- 239000002562 thickening agent Substances 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-I triphosphate(5-) Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O UNXRWKVEANCORM-UHFFFAOYSA-I 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229940108442 valtrex Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000007419 viral reactivation Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229940107931 zovirax Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28694801P | 2001-04-27 | 2001-04-27 | |
| US286948P | 2001-04-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2242028T3 true ES2242028T3 (es) | 2005-11-01 |
Family
ID=23100830
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02733945T Expired - Lifetime ES2242028T3 (es) | 2001-04-27 | 2002-04-05 | Derivados de pirazolo(1,5-a)piridina. |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US6962914B2 (https=) |
| EP (1) | EP1385847B1 (https=) |
| JP (1) | JP2004527560A (https=) |
| AT (1) | ATE296826T1 (https=) |
| AU (1) | AU2002305143A1 (https=) |
| DE (1) | DE60204452T2 (https=) |
| ES (1) | ES2242028T3 (https=) |
| WO (1) | WO2002088124A2 (https=) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20020506A1 (es) * | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| DE60112330T2 (de) * | 2000-12-15 | 2006-04-13 | Glaxo Group Ltd., Greenford | Pyrazolopyridinderivate |
| EP1366048B1 (en) * | 2001-03-08 | 2004-08-25 | SmithKline Beecham Corporation | Pyrazolopyridine derivatives |
| JP4219171B2 (ja) * | 2001-04-10 | 2009-02-04 | スミスクライン ビーチャム コーポレーション | 抗ウイルス性ピラゾロピリジン化合物 |
| DE60220525T2 (de) * | 2001-09-07 | 2008-02-07 | Smithkline Beecham Corp. | Pyrazolo-pyridine für die behandlung von herpes-ansteckungen |
| JP2005516916A (ja) * | 2001-12-11 | 2005-06-09 | スミスクライン ビーチャム コーポレーション | 抗ヘルペス薬としてのピラゾロ−ピリジン誘導体 |
| AU2003217712A1 (en) | 2002-03-07 | 2003-09-22 | Smithkline Beecham Corporation | Pyrazolopyrimidine and pyrazolotriazine derivatives and pharmaceutical compositions containing them |
| WO2006055245A2 (en) * | 2004-11-17 | 2006-05-26 | Smithkline Beecham Corporation | Process for preparing pyrazolopyridine compounds |
| US7812022B2 (en) * | 2004-12-21 | 2010-10-12 | Glaxosmithkline Llc | 2-pyrimidinyl pyrazolopyridine ErbB kinase inhibitors |
| CN101326182B (zh) * | 2005-12-05 | 2011-09-28 | 史密丝克莱恩比彻姆公司 | 2-嘧啶基吡唑并吡啶ErbB激酶抑制剂 |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| CN104945420A (zh) | 2009-06-29 | 2015-09-30 | 因塞特公司 | 作为pi3k抑制剂的嘧啶酮类 |
| US8680108B2 (en) * | 2009-12-18 | 2014-03-25 | Incyte Corporation | Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors |
| WO2011075643A1 (en) | 2009-12-18 | 2011-06-23 | Incyte Corporation | Substituted heteroaryl fused derivatives as pi3k inhibitors |
| AR081810A1 (es) | 2010-04-07 | 2012-10-24 | Bayer Cropscience Ag | Piridinilpirazoles biciclicos |
| AR081823A1 (es) | 2010-04-14 | 2012-10-24 | Incyte Corp | DERIVADOS FUSIONADOS COMO INHIBIDORES DE PI3Kd |
| US9062055B2 (en) | 2010-06-21 | 2015-06-23 | Incyte Corporation | Fused pyrrole derivatives as PI3K inhibitors |
| EP2402335A1 (en) | 2010-06-29 | 2012-01-04 | Basf Se | Pyrazolopyridine compounds |
| EP2402336A1 (en) | 2010-06-29 | 2012-01-04 | Basf Se | Pyrazolopyridine compounds |
| EP2655374B1 (en) | 2010-12-20 | 2019-10-23 | Incyte Holdings Corporation | N-(1-(substituted-phenyl)ethyl)-9h-purin-6-amines as pi3k inhibitors |
| CA2825825A1 (en) * | 2011-01-27 | 2012-08-02 | The Trustees Of Princeton University | Inhibitors of mtor kinase as anti-viral agents |
| US9108984B2 (en) | 2011-03-14 | 2015-08-18 | Incyte Corporation | Substituted diamino-pyrimidine and diamino-pyridine derivatives as PI3K inhibitors |
| WO2012135009A1 (en) | 2011-03-25 | 2012-10-04 | Incyte Corporation | Pyrimidine-4,6-diamine derivatives as pi3k inhibitors |
| KR102507287B1 (ko) | 2011-09-02 | 2023-03-07 | 인사이트 홀딩스 코포레이션 | Ｐｉ３ｋ 억제제로서 헤테로시클릴아민 |
| AR090548A1 (es) | 2012-04-02 | 2014-11-19 | Incyte Corp | Azaheterociclobencilaminas biciclicas como inhibidores de pi3k |
| WO2015191677A1 (en) | 2014-06-11 | 2015-12-17 | Incyte Corporation | Bicyclic heteroarylaminoalkyl phenyl derivatives as pi3k inhibitors |
| KR102431436B1 (ko) | 2014-08-29 | 2022-08-10 | 테스 파마 에스.알.엘. | α-아미노-β-카복시뮤콘산 세미알데히드 데카복실라제의 억제제 |
| SI3831833T1 (sl) | 2015-02-27 | 2023-03-31 | Incyte Holdings Corporation | Postopki za pripravo inhibitorja PI3K |
| US9732097B2 (en) | 2015-05-11 | 2017-08-15 | Incyte Corporation | Process for the synthesis of a phosphoinositide 3-kinase inhibitor |
| US9988401B2 (en) | 2015-05-11 | 2018-06-05 | Incyte Corporation | Crystalline forms of a PI3K inhibitor |
| EP3365340B1 (en) | 2015-10-19 | 2022-08-10 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| US20170145025A1 (en) | 2015-11-19 | 2017-05-25 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| ES2916874T3 (es) | 2015-12-17 | 2022-07-06 | Incyte Corp | Derivados de N-fenil-piridina-2-carboxamida y su uso como moduladores de la interacción proteína/proteína PD-1/PD-L1 |
| AU2016379372A1 (en) | 2015-12-22 | 2018-08-02 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| ES2906460T3 (es) | 2016-05-06 | 2022-04-18 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| ES2905980T3 (es) | 2016-05-26 | 2022-04-12 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| BR112018076534A2 (pt) | 2016-06-20 | 2019-04-02 | Incyte Corporation | compostos heterocíclicos como imunomoduladores |
| MA45669A (fr) | 2016-07-14 | 2019-05-22 | Incyte Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
| ES2941716T3 (es) | 2016-08-29 | 2023-05-25 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| EP3558990B1 (en) | 2016-12-22 | 2022-08-10 | Incyte Corporation | Tetrahydro imidazo[4,5-c]pyridine derivatives as pd-l1 internalization inducers |
| ES2899402T3 (es) | 2016-12-22 | 2022-03-11 | Incyte Corp | Derivados de piridina como inmunomoduladores |
| WO2018119286A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Bicyclic heteroaromatic compounds as immunomodulators |
| ES2874756T3 (es) | 2016-12-22 | 2021-11-05 | Incyte Corp | Derivados de triazolo[1,5-A]piridina como inmunomoduladores |
| AU2017382870B2 (en) | 2016-12-22 | 2022-03-24 | Incyte Corporation | Benzooxazole derivatives as immunomodulators |
| CR20200520A (es) | 2018-03-30 | 2021-03-09 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| WO2019217821A1 (en) | 2018-05-11 | 2019-11-14 | Incyte Corporation | Tetrahydro-imidazo[4,5-c]pyridine derivatives as pd-l1 immunomodulators |
| CA3101323A1 (en) | 2018-06-01 | 2019-12-05 | Incyte Corporation | Dosing regimen for the treatment of pi3k related disorders |
| EP4010342A1 (en) | 2019-08-09 | 2022-06-15 | Incyte Corporation | Salts of a pd-1/pd-l1 inhibitor |
| WO2021067217A1 (en) | 2019-09-30 | 2021-04-08 | Incyte Corporation | Pyrido[3,2-d]pyrimidine compounds as immunomodulators |
| BR112022009031A2 (pt) | 2019-11-11 | 2022-10-11 | Incyte Corp | Sais e formas cristalinas de um inibidor de pd-1/pd-l1 |
| US11866434B2 (en) | 2020-11-06 | 2024-01-09 | Incyte Corporation | Process for making a PD-1/PD-L1 inhibitor and salts and crystalline forms thereof |
| US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
| WO2022099075A1 (en) | 2020-11-06 | 2022-05-12 | Incyte Corporation | Crystalline form of a pd-1/pd-l1 inhibitor |
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| EP0151962A3 (en) | 1984-01-25 | 1985-10-02 | Beecham Group Plc | Pyrazolopyridine derivatives |
| GB8404586D0 (en) | 1984-02-22 | 1984-03-28 | Beecham Group Plc | Compounds |
| GB8404584D0 (en) | 1984-02-22 | 1984-03-28 | Beecham Group Plc | Compounds |
| US5002941A (en) | 1985-12-12 | 1991-03-26 | Smithkline Beecham Corporation | Pyrrolo(1,2-a)imidazole and imidazo(1,2-a)pyridine derivatives and their use as 5-lipoxygenase pathway inhibitors |
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| GB8901423D0 (en) | 1989-01-23 | 1989-03-15 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
| KR920702621A (ko) | 1989-06-13 | 1992-10-06 | 스튜어트 알. 슈터 | 단핵세포 및/또는 마크로파지에 의한 인터루킨-1 또는 종양회사인자 생성의 억제 |
| AU622330B2 (en) | 1989-06-23 | 1992-04-02 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds having a nitrogen atom in the bridgehead for use as fungicides |
| KR930700104A (ko) | 1990-06-12 | 1993-03-13 | 원본미기재 | 5-리프옥시게나제 및 사이클로옥시게나제 경로 개재된 질병의 억제 |
| GB9015764D0 (en) | 1990-07-18 | 1990-09-05 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
| DE69232323T2 (de) | 1991-01-29 | 2002-08-08 | Fujisawa Pharmaceutical Co., Ltd. | Verwendung von Adenosinantagonisten zur Vorbeugung und Behandlung von Pankreatitis und Ulcera |
| GB9107513D0 (en) | 1991-04-10 | 1991-05-29 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
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| EA199700209A1 (ru) | 1995-04-04 | 1998-04-30 | Глаксо Груп Лимитед | ПРОИЗВОДНЫЕ ИМИДАЗО[1,2-a]ПИРИДИНА |
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| US5700816A (en) | 1995-06-12 | 1997-12-23 | Isakson; Peter C. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor |
| US5670432A (en) | 1996-08-01 | 1997-09-23 | Taiwan Semiconductor Manufacturing Company, Ltd. | Thermal treatment to form a void free aluminum metal layer for a semiconductor device |
| FR2757166B1 (fr) | 1996-12-12 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derives du pyrrole, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2757059B1 (fr) | 1996-12-12 | 1999-01-29 | Rhone Poulenc Rorer Sa | Nouvelle application therapeutique des derives du pyrrole |
| CA2294057A1 (en) | 1997-06-13 | 1998-12-17 | Smithkline Beecham Corporation | Novel pyrazole and pyrazoline substituted compounds |
| ES2256817T3 (es) | 1997-09-05 | 2006-07-16 | Glaxo Group Limited | Composiciones farmaceuticas que comprenden derivados de 2,3-diaril-pirazolo(1,5-b)piridazina. |
| WO1999058523A1 (en) | 1998-05-14 | 1999-11-18 | G.D. Searle & Co. | 1,5-DIARYL SUBSTITUTED PYRAZOLES AS p38 KINASE INHIBITORS |
| US6245789B1 (en) | 1998-05-19 | 2001-06-12 | The Procter & Gamble Company | HIV and viral treatment |
| FR2779724B1 (fr) * | 1998-06-10 | 2001-04-20 | Rhone Poulenc Rorer Sa | Derives du pyrrole, leur preparation et les compositions pharmaceutiques qui les contiennent |
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| US20060092833A1 (en) * | 2004-11-02 | 2006-05-04 | Bemmel Jeroen V | Congestion control for improved management of service level agreements in switched networks |
-
2002
- 2002-04-05 AT AT02733945T patent/ATE296826T1/de not_active IP Right Cessation
- 2002-04-05 AU AU2002305143A patent/AU2002305143A1/en not_active Abandoned
- 2002-04-05 JP JP2002585423A patent/JP2004527560A/ja active Pending
- 2002-04-05 DE DE60204452T patent/DE60204452T2/de not_active Expired - Fee Related
- 2002-04-05 US US10/473,751 patent/US6962914B2/en not_active Expired - Fee Related
- 2002-04-05 EP EP02733945A patent/EP1385847B1/en not_active Expired - Lifetime
- 2002-04-05 WO PCT/US2002/010687 patent/WO2002088124A2/en not_active Ceased
- 2002-04-05 ES ES02733945T patent/ES2242028T3/es not_active Expired - Lifetime
-
2005
- 2005-03-31 US US11/095,212 patent/US7030134B2/en not_active Expired - Fee Related
- 2005-03-31 US US11/095,361 patent/US20050192295A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1385847A2 (en) | 2004-02-04 |
| US20050192303A1 (en) | 2005-09-01 |
| US6962914B2 (en) | 2005-11-08 |
| WO2002088124A3 (en) | 2003-05-08 |
| EP1385847B1 (en) | 2005-06-01 |
| ATE296826T1 (de) | 2005-06-15 |
| DE60204452D1 (de) | 2005-07-07 |
| JP2004527560A (ja) | 2004-09-09 |
| US7030134B2 (en) | 2006-04-18 |
| WO2002088124A2 (en) | 2002-11-07 |
| DE60204452T2 (de) | 2005-12-15 |
| AU2002305143A1 (en) | 2002-11-11 |
| US20040142941A1 (en) | 2004-07-22 |
| US20050192295A1 (en) | 2005-09-01 |
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