MX2007010460A - Compuestos de nucleosido triciclico para tratar infecciones virales. - Google Patents
Compuestos de nucleosido triciclico para tratar infecciones virales.Info
- Publication number
- MX2007010460A MX2007010460A MX2007010460A MX2007010460A MX2007010460A MX 2007010460 A MX2007010460 A MX 2007010460A MX 2007010460 A MX2007010460 A MX 2007010460A MX 2007010460 A MX2007010460 A MX 2007010460A MX 2007010460 A MX2007010460 A MX 2007010460A
- Authority
- MX
- Mexico
- Prior art keywords
- methyl
- benzo
- aza
- ribofuranosyl
- dihydro
- Prior art date
Links
- 208000036142 Viral infection Diseases 0.000 title claims abstract description 12
- 230000009385 viral infection Effects 0.000 title claims abstract description 11
- HOGVTUZUJGHKPL-HTVVRFAVSA-N triciribine Chemical class C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HOGVTUZUJGHKPL-HTVVRFAVSA-N 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims abstract description 37
- 241000700605 Viruses Species 0.000 claims abstract description 21
- 241000710781 Flaviviridae Species 0.000 claims abstract description 10
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 347
- -1 amino, aminocarbonyl Chemical group 0.000 claims description 126
- 229910052739 hydrogen Inorganic materials 0.000 claims description 124
- 239000001257 hydrogen Substances 0.000 claims description 118
- 239000000203 mixture Substances 0.000 claims description 113
- 241000711549 Hepacivirus C Species 0.000 claims description 62
- 229910052736 halogen Inorganic materials 0.000 claims description 56
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 50
- 150000002367 halogens Chemical group 0.000 claims description 50
- 150000002431 hydrogen Chemical group 0.000 claims description 48
- 229940002612 prodrug Drugs 0.000 claims description 48
- 239000000651 prodrug Chemical group 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 45
- 239000003814 drug Substances 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
- 125000004442 acylamino group Chemical group 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 150000001413 amino acids Chemical class 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- JPSJKKOBBFBOSB-UHFFFAOYSA-N 6h-azulen-5-one Chemical compound O=C1CC=CC2=CC=CC2=C1 JPSJKKOBBFBOSB-UHFFFAOYSA-N 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 17
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 17
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 17
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 16
- 229960000329 ribavirin Drugs 0.000 claims description 16
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 16
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 15
- BUJGEMBLEXNUBK-MENZVKOBSA-N CC(C)C[C@@H](C(=O)NS(=O)(=O)OC[C@@H]1[C@H]([C@H]([C@@H](CO1)CCCN2C=C(N=N2)CNC(=O)NCC3=CC=CC=C3)O)O)N Chemical group CC(C)C[C@@H](C(=O)NS(=O)(=O)OC[C@@H]1[C@H]([C@H]([C@@H](CO1)CCCN2C=C(N=N2)CNC(=O)NCC3=CC=CC=C3)O)O)N BUJGEMBLEXNUBK-MENZVKOBSA-N 0.000 claims description 14
- 108010047761 Interferon-alpha Proteins 0.000 claims description 14
- 102000006992 Interferon-alpha Human genes 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 239000003112 inhibitor Substances 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 239000013543 active substance Substances 0.000 claims description 10
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 229910052721 tungsten Inorganic materials 0.000 claims description 10
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 8
- IWUCXVSUMQZMFG-RGDLXGNYSA-N 1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 IWUCXVSUMQZMFG-RGDLXGNYSA-N 0.000 claims description 7
- 108060004795 Methyltransferase Proteins 0.000 claims description 7
- 229910052727 yttrium Inorganic materials 0.000 claims description 6
- BLURITVAGFDMPS-NHULRPGXSA-N (2R,3R,4R,5R)-2-(3,5,7,9,10,12-hexazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-3-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NNC=N3)=C2C3=C1 BLURITVAGFDMPS-NHULRPGXSA-N 0.000 claims description 5
- IXXVTGLQEGPRLV-KNJXUWEQSA-N (2R,3R,4R,5R)-5-(hydroxymethyl)-3-methyl-2-(3,5,7,9,10-pentazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-3-yl)oxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NNC=C3)=C2C3=C1 IXXVTGLQEGPRLV-KNJXUWEQSA-N 0.000 claims description 5
- ZKJIVMQMKMMFHI-FTTKWNSESA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-11-fluoro-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C(F)=C3)=C2C3=C1 ZKJIVMQMKMMFHI-FTTKWNSESA-N 0.000 claims description 5
- 101710088194 Dehydrogenase Proteins 0.000 claims description 5
- GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 claims description 5
- JIPYIHALDIWXLT-FPOOMLEOSA-N N-[3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-12-yl]acetamide Chemical compound C1=C(C2=3)C(NC(=O)C)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O JIPYIHALDIWXLT-FPOOMLEOSA-N 0.000 claims description 5
- 108091005804 Peptidases Proteins 0.000 claims description 5
- 239000004365 Protease Substances 0.000 claims description 5
- SPHINGCEMHXYKE-VHQAPHLWSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9,10,12-hexazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-11-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NNC(=O)N3)=C2C3=C1 SPHINGCEMHXYKE-VHQAPHLWSA-N 0.000 claims description 4
- NIAJWNYWHQCZHB-YTUKDDMISA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9,12-pentazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-11-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NCC(=O)N3)=C2C3=C1 NIAJWNYWHQCZHB-YTUKDDMISA-N 0.000 claims description 4
- XUJHVFLLGKRHTE-ZCLWBALQSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene-10,12-dione Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)CC3=O)=C2C3=C1 XUJHVFLLGKRHTE-ZCLWBALQSA-N 0.000 claims description 4
- 102000016600 Inosine-5'-monophosphate dehydrogenases Human genes 0.000 claims description 4
- 108050006182 Inosine-5'-monophosphate dehydrogenases Proteins 0.000 claims description 4
- 235000013902 inosinic acid Nutrition 0.000 claims description 4
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 claims description 4
- 229950006081 taribavirin Drugs 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- GRMYVLYSBJYKBE-ZCLWBALQSA-N 12-chloro-3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3Cl)=C2C3=C1 GRMYVLYSBJYKBE-ZCLWBALQSA-N 0.000 claims description 3
- OAHNQJQLXDEFCL-ZCLWBALQSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-(hydroxyamino)-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NO)=C2C3=C1 OAHNQJQLXDEFCL-ZCLWBALQSA-N 0.000 claims description 3
- GVOOKYOKQRCJFT-KHTZZEJVSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-(methoxyamino)-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C1=C(C2=3)C(NOC)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O GVOOKYOKQRCJFT-KHTZZEJVSA-N 0.000 claims description 3
- WEBPMOZRCPJYAW-ZCLWBALQSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-fluoro-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3F)=C2C3=C1 WEBPMOZRCPJYAW-ZCLWBALQSA-N 0.000 claims description 3
- YDTPSIYKHMTGKX-PZTHBURQSA-N 9-amino-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6-tetraaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C=C(N)C3=C1 YDTPSIYKHMTGKX-PZTHBURQSA-N 0.000 claims description 3
- YCXPYXMDZXJQKB-QTDMDRALSA-N 9-carbamoyl-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6-tetraaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C=C(C(N)=O)C3=C1 YCXPYXMDZXJQKB-QTDMDRALSA-N 0.000 claims description 3
- JKGHPHSYUAVDSB-UIBBOPPKSA-N 9-cyano-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6-tetraaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C=C(C#N)C3=C1 JKGHPHSYUAVDSB-UIBBOPPKSA-N 0.000 claims description 3
- CDWPLWQNOLTUNM-PZTHBURQSA-N 9-iodo-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6-tetraaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C=C(I)C3=C1 CDWPLWQNOLTUNM-PZTHBURQSA-N 0.000 claims description 3
- 101800001019 Non-structural protein 4B Proteins 0.000 claims description 3
- 101800001014 Non-structural protein 5A Proteins 0.000 claims description 3
- 102000035195 Peptidases Human genes 0.000 claims description 3
- 229910006069 SO3H Inorganic materials 0.000 claims description 3
- 101800001098 Serine protease NS3 Proteins 0.000 claims description 3
- 108010046075 Thymosin Proteins 0.000 claims description 3
- 102000007501 Thymosin Human genes 0.000 claims description 3
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 claims description 3
- 229910052720 vanadium Inorganic materials 0.000 claims description 3
- GLOQJXCSHIAUSF-ZCLWBALQSA-N 12-amino-3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaene-10-thione Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=S)C=C3N)=C2C3=C1 GLOQJXCSHIAUSF-ZCLWBALQSA-N 0.000 claims description 2
- XEQDJLRBBKBFBE-ZCLWBALQSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-hydrazinyl-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NN)=C2C3=C1 XEQDJLRBBKBFBE-ZCLWBALQSA-N 0.000 claims description 2
- CKPBDTBZKMEWOU-KHTZZEJVSA-N N-[3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-12-yl]formamide Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NC=O)=C2C3=C1 CKPBDTBZKMEWOU-KHTZZEJVSA-N 0.000 claims description 2
- UVUFIBDXCNFICN-YTUKDDMISA-N [[(2R,3R,4R,5R)-3,4-dihydroxy-4-methyl-5-(11-oxo-3,5,7,9,12-pentazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-3-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NCC(=O)N3)=C2C3=C1 UVUFIBDXCNFICN-YTUKDDMISA-N 0.000 claims description 2
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- KYDZVISIOSNRMR-KXOWALFDSA-N 12-amino-3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-11-fluoro-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C(F)=C3N)=C2C3=C1 KYDZVISIOSNRMR-KXOWALFDSA-N 0.000 claims 1
- SFQUTMMHSCDERR-YTUKDDMISA-N 2-(2'-methyl-β-d-ribofuranosyl)-2,9-dihydro-6h-2,3,5,6,9-pentaaza-benzo[cd]azulene-7,8-dione Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C(=O)NC3=C1 SFQUTMMHSCDERR-YTUKDDMISA-N 0.000 claims 1
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- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
- 229960004231 thymalfasin Drugs 0.000 description 1
- 230000006016 thyroid dysfunction Effects 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 229940044616 toll-like receptor 7 agonist Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229950002810 valopicitabine Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/22—Pteridine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/23—Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65746305P | 2005-02-28 | 2005-02-28 | |
| PCT/US2006/007132 WO2006093987A1 (en) | 2005-02-28 | 2006-02-28 | Tricyclic-nucleoside compounds for treating viral infections |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007010460A true MX2007010460A (es) | 2007-11-08 |
Family
ID=36570903
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007010460A MX2007010460A (es) | 2005-02-28 | 2006-02-28 | Compuestos de nucleosido triciclico para tratar infecciones virales. |
| MX2007010463A MX2007010463A (es) | 2005-02-28 | 2006-02-28 | Profarmacos de nucleosido triciclico para tratar infecciones virales. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007010463A MX2007010463A (es) | 2005-02-28 | 2006-02-28 | Profarmacos de nucleosido triciclico para tratar infecciones virales. |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US7524825B2 (https=) |
| EP (2) | EP1853618A1 (https=) |
| JP (2) | JP2008531704A (https=) |
| KR (2) | KR20070106767A (https=) |
| CN (2) | CN101142226A (https=) |
| AP (2) | AP2007004128A0 (https=) |
| AR (1) | AR058419A1 (https=) |
| AU (2) | AU2006218705A1 (https=) |
| BR (2) | BRPI0607770A2 (https=) |
| CA (2) | CA2597685A1 (https=) |
| EA (2) | EA200701849A1 (https=) |
| HR (2) | HRP20070436A2 (https=) |
| IL (2) | IL184954A0 (https=) |
| MX (2) | MX2007010460A (https=) |
| NO (2) | NO20074613L (https=) |
| TW (1) | TW200640474A (https=) |
| WO (2) | WO2006093986A1 (https=) |
| ZA (1) | ZA200707410B (https=) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1863813B (zh) | 2003-08-27 | 2011-03-30 | 生物区科学管理控股有限公司 | 作为治疗剂的三环核苷或核苷酸 |
| HRP20070436A2 (hr) * | 2005-02-28 | 2008-02-29 | Genelabs Technologies | Triciklički nukleozidni predlijekovi za liječenjevirusnih infekcija |
| AR056327A1 (es) * | 2005-04-25 | 2007-10-03 | Genelabs Tech Inc | Compuestos de nucleosidos para el tratamiento de infecciones virales |
| US20080261913A1 (en) | 2006-12-28 | 2008-10-23 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of liver disorders |
| PT2144604E (pt) | 2007-02-28 | 2011-10-19 | Conatus Pharmaceuticals Inc | Métodos para o tratamento da hepatite c viral crónica utilizando ro-113-0830 |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| WO2009029729A1 (en) * | 2007-08-31 | 2009-03-05 | Genelabs Technologies, Inc. | Amino tricyclic-nucleoside compounds, compositions, and methods of use |
| GB0718575D0 (en) * | 2007-09-24 | 2007-10-31 | Angeletti P Ist Richerche Bio | Nucleoside derivatives as inhibitors of viral polymerases |
| TW200942243A (en) | 2008-03-05 | 2009-10-16 | Biocryst Pharm Inc | Antiviral therapeutic agents |
| GB2471806B (en) * | 2008-04-03 | 2012-12-19 | Spring Bank Pharmaceuticals Inc | Compositions and methods for treating viral infections |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| KR20110098849A (ko) | 2008-12-23 | 2011-09-01 | 파마셋 인코포레이티드 | 뉴클레오시드 유사체 |
| PT2376088T (pt) | 2008-12-23 | 2017-05-02 | Gilead Pharmasset Llc | Fosforamidatos de nucleósidos de 2-amino-purina 6-osubstituída |
| SG194404A1 (en) | 2008-12-23 | 2013-11-29 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| GB0900914D0 (en) * | 2009-01-20 | 2009-03-04 | Angeletti P Ist Richerche Bio | Antiviral agents |
| TW201102390A (en) * | 2009-03-31 | 2011-01-16 | Arqule Inc | Substituted pyrazolo-pyrimidine compounds |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| TWI598358B (zh) | 2009-05-20 | 2017-09-11 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| PT2609923T (pt) | 2010-03-31 | 2017-08-30 | Gilead Pharmasset Llc | Processo para a cristalização de 2-(((s)- (perfluorofenoxi)(fenoxi)fosforil)amino)propanoato de (s)-isopropilo |
| PL3290428T3 (pl) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu |
| UY33312A (es) | 2010-03-31 | 2011-10-31 | Pharmasset Inc | Fosforamidato de nucleosido de purina |
| MX2012011222A (es) | 2010-04-01 | 2013-01-18 | Centre Nat Rech Scient | Compuestos y composiciones farmaceuticas para el tratamiento de infecciones virales. |
| AU2011336632B2 (en) | 2010-11-30 | 2015-09-03 | Gilead Pharmasset Llc | Compounds |
| EP2691409B1 (en) | 2011-03-31 | 2018-02-21 | Idenix Pharmaceuticals LLC. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| KR20140064765A (ko) | 2011-06-30 | 2014-05-28 | 스텔라 에이피에스 | Hcv 조합 치료 |
| WO2013033093A1 (en) * | 2011-08-29 | 2013-03-07 | Biocryst Pharmaceuticals, Inc. | Heterocyclic compounds as janus kinase inhibitors |
| TW201329096A (zh) | 2011-09-12 | 2013-07-16 | Idenix Pharmaceuticals Inc | 經取代羰氧基甲基磷酸醯胺化合物及用於治療病毒感染之藥學組成物 |
| PL2709613T5 (pl) | 2011-09-16 | 2020-12-14 | Gilead Pharmasset Llc | Metody leczenia hcv |
| US8507460B2 (en) | 2011-10-14 | 2013-08-13 | Idenix Pharmaceuticals, Inc. | Substituted 3′,5′-cyclic phosphates of purine nucleotide compounds and pharmaceutical compositions for the treatment of viral infections |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| EP2639238A1 (en) * | 2012-03-15 | 2013-09-18 | Universität Bern | Tricyclic nucleosides and oligomeric compounds prepared therefrom |
| AR090699A1 (es) * | 2012-04-18 | 2014-12-03 | Biocryst Pharm Inc | Compuestos inhibidores de la actividad de la arn polimerasa viral |
| US9296778B2 (en) | 2012-05-22 | 2016-03-29 | Idenix Pharmaceuticals, Inc. | 3′,5′-cyclic phosphate prodrugs for HCV infection |
| WO2013177188A1 (en) | 2012-05-22 | 2013-11-28 | Idenix Pharmaceuticals, Inc. | 3',5'-cyclic phosphoramidate prodrugs for hcv infection |
| CA2873315A1 (en) | 2012-05-22 | 2013-11-28 | Idenix Pharamaceuticals, Inc. | D-amino acid compounds for liver disease |
| SG11201407336PA (en) | 2012-05-25 | 2015-03-30 | Janssen Sciences Ireland Uc | Uracyl spirooxetane nucleosides |
| WO2014052638A1 (en) | 2012-09-27 | 2014-04-03 | Idenix Pharmaceuticals, Inc. | Esters and malonates of sate prodrugs |
| KR102001280B1 (ko) | 2012-10-08 | 2019-07-17 | 아이데닉스 파마슈티칼스 엘엘씨 | Hcv 감염에 대한 2'-클로로 뉴클레오시드 유사체 |
| WO2014066239A1 (en) | 2012-10-22 | 2014-05-01 | Idenix Pharmaceuticals, Inc. | 2',4'-bridged nucleosides for hcv infection |
| EP2935304A1 (en) | 2012-12-19 | 2015-10-28 | IDENIX Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
| PT2950786T (pt) | 2013-01-31 | 2020-03-03 | Gilead Pharmasset Llc | Formulação de combinação de dois compostos antivirais |
| US9309275B2 (en) | 2013-03-04 | 2016-04-12 | Idenix Pharmaceuticals Llc | 3′-deoxy nucleosides for the treatment of HCV |
| US9339541B2 (en) | 2013-03-04 | 2016-05-17 | Merck Sharp & Dohme Corp. | Thiophosphate nucleosides for the treatment of HCV |
| WO2014160484A1 (en) | 2013-03-13 | 2014-10-02 | Idenix Pharmaceuticals, Inc. | Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv |
| EP2981542B1 (en) | 2013-04-01 | 2021-09-15 | Idenix Pharmaceuticals LLC | 2',4'-fluoro nucleosides for the treatment of hcv |
| US10005779B2 (en) | 2013-06-05 | 2018-06-26 | Idenix Pharmaceuticals Llc | 1′,4′-thio nucleosides for the treatment of HCV |
| WO2015017713A1 (en) | 2013-08-01 | 2015-02-05 | Idenix Pharmaceuticals, Inc. | D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease |
| EA201690473A1 (ru) | 2013-08-27 | 2017-03-31 | ГАЙЛИД ФАРМАССЕТ ЭлЭлСи | Комбинированный состав двух противовирусных соединений |
| WO2015161137A1 (en) | 2014-04-16 | 2015-10-22 | Idenix Pharmaceuticals, Inc. | 3'-substituted methyl or alkynyl nucleosides for the treatment of hcv |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4107288A (en) * | 1974-09-18 | 1978-08-15 | Pharmaceutical Society Of Victoria | Injectable compositions, nanoparticles useful therein, and process of manufacturing same |
| ATE270326T1 (de) | 1990-04-04 | 2004-07-15 | Chiron Corp | Protease von hepatitis-c-virus |
| US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| DE69434931T2 (de) | 1993-04-02 | 2007-11-22 | Rigel Pharmaceuticals, Inc., South San Francisco | Methode zur selektiven inaktivierung der viralen replication |
| IT1272179B (it) | 1994-02-23 | 1997-06-16 | Angeletti P Ist Richerche Bio | Metodologia per riprodurre in vitro l'attivita' proteolitica della proteasi ns3 del virus hcv. |
| US5861267A (en) * | 1995-05-01 | 1999-01-19 | Vertex Pharmaceuticals Incorporated | Methods, nucleotide sequences and host cells for assaying exogenous and endogenous protease activity |
| EP0859833B1 (en) | 1995-09-27 | 2006-03-01 | Emory University | Recombinant hepatitis c virus rna replicase |
| US5759795A (en) * | 1996-03-08 | 1998-06-02 | Schering Corporation | Assay for determining inhibitors of ATPase |
| JP2001514508A (ja) | 1997-03-05 | 2001-09-11 | ユニバーシティー オブ ワシントン | Ｃ型肝炎ウイルスの複製を選択的に抑制する薬剤を同定するための新規なスクリーニング法 |
| EP0973788A1 (en) | 1997-04-02 | 2000-01-26 | Amersham Pharmacia Biotech UK Limited | Tricyclic base analogues |
| US6228576B1 (en) * | 1997-12-11 | 2001-05-08 | Smithkline Beecham Corporation | Hepatitis C virus NS5B truncated protein and methods thereof to identify antiviral compounds |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| US20030008841A1 (en) | 2000-08-30 | 2003-01-09 | Rene Devos | Anti-HCV nucleoside derivatives |
| WO2002057425A2 (en) * | 2001-01-22 | 2002-07-25 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| WO2003061385A1 (en) * | 2002-01-17 | 2003-07-31 | Ribapharm Inc. | Tricyclic nucleoside library compounds, synthesis, and use as antiviral agents |
| WO2004014852A2 (en) | 2002-08-12 | 2004-02-19 | Bristol-Myers Squibb Company | Iminothiazolidinones as inhibitors of hcv replication |
| EP2345657A1 (en) | 2003-05-30 | 2011-07-20 | Pharmasset, Inc. | Modified fluorinated nucleoside analogues |
| CN1863813B (zh) * | 2003-08-27 | 2011-03-30 | 生物区科学管理控股有限公司 | 作为治疗剂的三环核苷或核苷酸 |
| US7144868B2 (en) * | 2003-10-27 | 2006-12-05 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
| JP2007509939A (ja) * | 2003-10-27 | 2007-04-19 | ジェネラブズ テクノロジーズ インコーポレーティッド | ウイルス感染を治療するためのヌクレオシド化合物 |
| US7202223B2 (en) | 2003-10-27 | 2007-04-10 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
| HRP20070436A2 (hr) | 2005-02-28 | 2008-02-29 | Genelabs Technologies | Triciklički nukleozidni predlijekovi za liječenjevirusnih infekcija |
-
2006
- 2006-02-28 HR HR20070436A patent/HRP20070436A2/xx not_active Application Discontinuation
- 2006-02-28 CA CA002597685A patent/CA2597685A1/en not_active Abandoned
- 2006-02-28 MX MX2007010460A patent/MX2007010460A/es not_active Application Discontinuation
- 2006-02-28 BR BRPI0607770-6A patent/BRPI0607770A2/pt not_active IP Right Cessation
- 2006-02-28 AP AP2007004128A patent/AP2007004128A0/xx unknown
- 2006-02-28 CN CNA2006800063894A patent/CN101142226A/zh active Pending
- 2006-02-28 JP JP2007558142A patent/JP2008531704A/ja not_active Withdrawn
- 2006-02-28 ZA ZA200707410A patent/ZA200707410B/xx unknown
- 2006-02-28 EP EP06736451A patent/EP1853618A1/en not_active Withdrawn
- 2006-02-28 KR KR1020077020680A patent/KR20070106767A/ko not_active Withdrawn
- 2006-02-28 AP AP2007004118A patent/AP2007004118A0/xx unknown
- 2006-02-28 EA EA200701849A patent/EA200701849A1/ru unknown
- 2006-02-28 US US11/365,321 patent/US7524825B2/en not_active Expired - Fee Related
- 2006-02-28 MX MX2007010463A patent/MX2007010463A/es not_active Application Discontinuation
- 2006-02-28 AR ARP060100751A patent/AR058419A1/es unknown
- 2006-02-28 CN CNA2006800063907A patent/CN101128474A/zh active Pending
- 2006-02-28 EA EA200701850A patent/EA200701850A1/ru unknown
- 2006-02-28 WO PCT/US2006/007131 patent/WO2006093986A1/en not_active Ceased
- 2006-02-28 EP EP06736450A patent/EP1853617A1/en not_active Withdrawn
- 2006-02-28 KR KR1020077021265A patent/KR20070106781A/ko not_active Withdrawn
- 2006-02-28 AU AU2006218705A patent/AU2006218705A1/en not_active Abandoned
- 2006-02-28 AU AU2006218704A patent/AU2006218704A1/en not_active Abandoned
- 2006-02-28 US US11/365,170 patent/US7534771B2/en not_active Expired - Fee Related
- 2006-02-28 CA CA002597683A patent/CA2597683A1/en not_active Abandoned
- 2006-02-28 BR BRPI0607769-2A patent/BRPI0607769A2/pt not_active IP Right Cessation
- 2006-02-28 WO PCT/US2006/007132 patent/WO2006093987A1/en not_active Ceased
- 2006-02-28 JP JP2007558141A patent/JP2008531703A/ja not_active Withdrawn
- 2006-02-28 HR HR20070435A patent/HRP20070435A9/xx not_active Application Discontinuation
- 2006-03-01 TW TW095106861A patent/TW200640474A/zh unknown
-
2007
- 2007-07-31 IL IL184954A patent/IL184954A0/en unknown
- 2007-07-31 IL IL184955A patent/IL184955A0/en unknown
- 2007-09-11 NO NO20074613A patent/NO20074613L/no not_active Application Discontinuation
- 2007-09-27 NO NO20074915A patent/NO20074915L/no not_active Application Discontinuation
-
2009
- 2009-03-31 US US12/415,286 patent/US20090208457A1/en not_active Abandoned
- 2009-03-31 US US12/415,335 patent/US20090253648A1/en not_active Abandoned
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Legal Events
| Date | Code | Title | Description |
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| FA | Abandonment or withdrawal |