JP2012528867A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2012528867A5 JP2012528867A5 JP2012514047A JP2012514047A JP2012528867A5 JP 2012528867 A5 JP2012528867 A5 JP 2012528867A5 JP 2012514047 A JP2012514047 A JP 2012514047A JP 2012514047 A JP2012514047 A JP 2012514047A JP 2012528867 A5 JP2012528867 A5 JP 2012528867A5
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- nucleotide
- guanosine
- deaza
- cytosine
- 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.)
- Granted
Links
- 125000003729 nucleotide group Chemical group 0.000 claims description 41
- 108091034117 Oligonucleotide Proteins 0.000 claims description 32
- 239000002773 nucleotide Substances 0.000 claims description 28
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 26
- 230000003308 immunostimulating effect Effects 0.000 claims description 9
- 108020000411 Toll-like receptor Proteins 0.000 claims description 7
- 102000002689 Toll-like receptor Human genes 0.000 claims description 7
- 239000005557 antagonist Substances 0.000 claims description 7
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 7
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 7
- 230000002519 immonomodulatory effect Effects 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims 19
- 239000002342 ribonucleoside Substances 0.000 claims 16
- 150000008209 arabinosides Chemical class 0.000 claims 12
- 125000004432 carbon atom Chemical group C* 0.000 claims 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 12
- 125000005843 halogen group Chemical group 0.000 claims 12
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 12
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims 9
- 125000003118 aryl group Chemical group 0.000 claims 9
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 9
- 201000010099 disease Diseases 0.000 claims 8
- -1 carboalkoxy Chemical group 0.000 claims 7
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 claims 6
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims 6
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 6
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims 6
- 125000002252 acyl group Chemical group 0.000 claims 6
- 125000004423 acyloxy group Chemical group 0.000 claims 6
- 125000003545 alkoxy group Chemical group 0.000 claims 6
- 230000001363 autoimmune Effects 0.000 claims 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims 6
- 229940104302 cytosine Drugs 0.000 claims 6
- 229940029575 guanosine Drugs 0.000 claims 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
- 230000002757 inflammatory effect Effects 0.000 claims 6
- DRAVOWXCEBXPTN-UHFFFAOYSA-N isoguanine Chemical compound NC1=NC(=O)NC2=C1NC=N2 DRAVOWXCEBXPTN-UHFFFAOYSA-N 0.000 claims 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 6
- 229920006395 saturated elastomer Polymers 0.000 claims 6
- 238000006467 substitution reaction Methods 0.000 claims 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 6
- NYHBQMYGNKIUIF-FJFJXFQQSA-N 9-beta-D-arabinofuranosylguanine Chemical compound C12=NC(N)=NC(O)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O NYHBQMYGNKIUIF-FJFJXFQQSA-N 0.000 claims 5
- 108010008165 Etanercept Proteins 0.000 claims 4
- 241000124008 Mammalia Species 0.000 claims 4
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 claims 4
- 208000035475 disorder Diseases 0.000 claims 4
- 229960000403 etanercept Drugs 0.000 claims 4
- 229960000598 infliximab Drugs 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims 3
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 claims 3
- IQFYYKKMVGJFEH-BIIVOSGPSA-N 2'-deoxythymidine Natural products O=C1NC(=O)C(C)=CN1[C@@H]1O[C@@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-BIIVOSGPSA-N 0.000 claims 3
- JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 claims 3
- RBYIXGAYDLAKCC-GXTPVXIHSA-N 2-amino-7-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,5-dihydropyrrolo[3,2-d]pyrimidin-4-one Chemical compound C=1NC=2C(=O)NC(N)=NC=2C=1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RBYIXGAYDLAKCC-GXTPVXIHSA-N 0.000 claims 3
- RFHIWBUKNJIBSE-KQYNXXCUSA-N 2-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-methylpurin-9-ium-6-thiolate Chemical compound C12=NC(N)=NC([S-])=C2N(C)C=[N+]1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RFHIWBUKNJIBSE-KQYNXXCUSA-N 0.000 claims 3
- RNSGUQLXDMZREX-SDBHATRESA-N 2-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-phenylmethoxy-3h-purin-6-one Chemical compound C=1C=CC=CC=1COC1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RNSGUQLXDMZREX-SDBHATRESA-N 0.000 claims 3
- SGEBAMRXAPOEIN-UHFFFAOYSA-N 2-amino-9-hexyl-3h-purin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N(CCCCCC)C=N2 SGEBAMRXAPOEIN-UHFFFAOYSA-N 0.000 claims 3
- VIVLSUIQHWGALQ-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound NC1=NC(Cl)=C2C=CNC2=N1 VIVLSUIQHWGALQ-UHFFFAOYSA-N 0.000 claims 3
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 claims 3
- TVICROIWXBFQEL-UHFFFAOYSA-N 6-(ethylamino)-1h-pyrimidin-2-one Chemical compound CCNC1=CC=NC(=O)N1 TVICROIWXBFQEL-UHFFFAOYSA-N 0.000 claims 3
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims 3
- NLLCDONDZDHLCI-UHFFFAOYSA-N 6-amino-5-hydroxy-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1O NLLCDONDZDHLCI-UHFFFAOYSA-N 0.000 claims 3
- OGHAROSJZRTIOK-KQYNXXCUSA-O 7-methylguanosine Chemical compound C1=2N=C(N)NC(=O)C=2[N+](C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OGHAROSJZRTIOK-KQYNXXCUSA-O 0.000 claims 3
- ASUCSHXLTWZYBA-UMMCILCDSA-N 8-Bromoguanosine Chemical compound C1=2NC(N)=NC(=O)C=2N=C(Br)N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ASUCSHXLTWZYBA-UMMCILCDSA-N 0.000 claims 3
- FPGSEBKFEJEOSA-UMMCILCDSA-N 8-Hydroxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O FPGSEBKFEJEOSA-UMMCILCDSA-N 0.000 claims 3
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 3
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 claims 3
- RSPURTUNRHNVGF-IOSLPCCCSA-N N(2),N(2)-dimethylguanosine Chemical compound C1=NC=2C(=O)NC(N(C)C)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RSPURTUNRHNVGF-IOSLPCCCSA-N 0.000 claims 3
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 claims 3
- 102100039390 Toll-like receptor 7 Human genes 0.000 claims 3
- 102100033117 Toll-like receptor 9 Human genes 0.000 claims 3
- 125000003277 amino group Chemical group 0.000 claims 3
- 150000005840 aryl radicals Chemical class 0.000 claims 3
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 claims 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 3
- 229960000684 cytarabine Drugs 0.000 claims 3
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims 3
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 claims 3
- 235000011187 glycerol Nutrition 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 230000004936 stimulating effect Effects 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- 229960003087 tioguanine Drugs 0.000 claims 3
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 claims 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims 2
- UNVGBIALRHLALK-UHFFFAOYSA-N 1,5-Hexanediol Chemical compound CC(O)CCCCO UNVGBIALRHLALK-UHFFFAOYSA-N 0.000 claims 2
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 claims 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 claims 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 2
- 208000011231 Crohn disease Diseases 0.000 claims 2
- 108010041986 DNA Vaccines Proteins 0.000 claims 2
- 229940021995 DNA vaccine Drugs 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 201000004681 Psoriasis Diseases 0.000 claims 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims 2
- 206010046851 Uveitis Diseases 0.000 claims 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 239000000556 agonist Substances 0.000 claims 2
- 239000013566 allergen Substances 0.000 claims 2
- 229960004784 allergens Drugs 0.000 claims 2
- 239000003242 anti bacterial agent Substances 0.000 claims 2
- 229940088710 antibiotic agent Drugs 0.000 claims 2
- 239000000427 antigen Substances 0.000 claims 2
- 102000036639 antigens Human genes 0.000 claims 2
- 108091007433 antigens Proteins 0.000 claims 2
- 239000000074 antisense oligonucleotide Substances 0.000 claims 2
- 238000012230 antisense oligonucleotides Methods 0.000 claims 2
- 239000003443 antiviral agent Substances 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 206010009887 colitis Diseases 0.000 claims 2
- 230000004940 costimulation Effects 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- 239000002254 cytotoxic agent Substances 0.000 claims 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims 2
- GHLKSLMMWAKNBM-UHFFFAOYSA-N dodecane-1,12-diol Chemical compound OCCCCCCCCCCCCO GHLKSLMMWAKNBM-UHFFFAOYSA-N 0.000 claims 2
- VCCRNZQBSJXYJD-UHFFFAOYSA-N galangin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=CC=C1 VCCRNZQBSJXYJD-UHFFFAOYSA-N 0.000 claims 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims 2
- 238000001415 gene therapy Methods 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 201000000306 sarcoidosis Diseases 0.000 claims 2
- 229960005486 vaccine Drugs 0.000 claims 2
- 239000013598 vector Substances 0.000 claims 2
- NSMOSDAEGJTOIQ-CRCLSJGQSA-N (2r,3s)-2-(hydroxymethyl)oxolan-3-ol Chemical compound OC[C@H]1OCC[C@@H]1O NSMOSDAEGJTOIQ-CRCLSJGQSA-N 0.000 claims 1
- ZWVMLYRJXORSEP-UHFFFAOYSA-N 1,2,6-Hexanetriol Chemical compound OCCCCC(O)CO ZWVMLYRJXORSEP-UHFFFAOYSA-N 0.000 claims 1
- 229940015975 1,2-hexanediol Drugs 0.000 claims 1
- 229940031723 1,2-octanediol Drugs 0.000 claims 1
- LMMTVYUCEFJZLC-UHFFFAOYSA-N 1,3,5-pentanetriol Chemical compound OCCC(O)CCO LMMTVYUCEFJZLC-UHFFFAOYSA-N 0.000 claims 1
- BPXVHIRIPLPOPT-UHFFFAOYSA-N 1,3,5-tris(2-hydroxyethyl)-1,3,5-triazinane-2,4,6-trione Chemical compound OCCN1C(=O)N(CCO)C(=O)N(CCO)C1=O BPXVHIRIPLPOPT-UHFFFAOYSA-N 0.000 claims 1
- ODMOFUHYUDOOFU-UHFFFAOYSA-N 1,3-bis(2-hydroxyethoxy)propan-2-ol Chemical compound OCCOCC(O)COCCO ODMOFUHYUDOOFU-UHFFFAOYSA-N 0.000 claims 1
- OXHWCYGEPMSVOG-UHFFFAOYSA-N 1,3-bis(3-hydroxypropoxy)propan-2-ol Chemical compound OCCCOCC(O)COCCCO OXHWCYGEPMSVOG-UHFFFAOYSA-N 0.000 claims 1
- ALVZNPYWJMLXKV-UHFFFAOYSA-N 1,9-Nonanediol Chemical compound OCCCCCCCCCO ALVZNPYWJMLXKV-UHFFFAOYSA-N 0.000 claims 1
- SYZUAYUNLUCJLW-UHFFFAOYSA-N 2-(1-aminopropyl)propane-1,3-diol Chemical compound CCC(N)C(CO)CO SYZUAYUNLUCJLW-UHFFFAOYSA-N 0.000 claims 1
- OLQJQHSAWMFDJE-UHFFFAOYSA-N 2-(hydroxymethyl)-2-nitropropane-1,3-diol Chemical compound OCC(CO)(CO)[N+]([O-])=O OLQJQHSAWMFDJE-UHFFFAOYSA-N 0.000 claims 1
- SYNPRNNJJLRHTI-UHFFFAOYSA-N 2-(hydroxymethyl)butane-1,4-diol Chemical compound OCCC(CO)CO SYNPRNNJJLRHTI-UHFFFAOYSA-N 0.000 claims 1
- SFRDXVJWXWOTEW-UHFFFAOYSA-N 2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(CO)CO SFRDXVJWXWOTEW-UHFFFAOYSA-N 0.000 claims 1
- IKFWPXJYAIJZES-UHFFFAOYSA-N 3,5-bis(hydroxymethyl)phenol Chemical compound OCC1=CC(O)=CC(CO)=C1 IKFWPXJYAIJZES-UHFFFAOYSA-N 0.000 claims 1
- AHHQDHCTHYTBSV-UHFFFAOYSA-N 3-methylpentane-1,3,5-triol Chemical compound OCCC(O)(C)CCO AHHQDHCTHYTBSV-UHFFFAOYSA-N 0.000 claims 1
- ALQSHHUCVQOPAS-UHFFFAOYSA-N Pentane-1,5-diol Chemical compound OCCCCCO ALQSHHUCVQOPAS-UHFFFAOYSA-N 0.000 claims 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N Tetraethylene glycol, Natural products OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 claims 1
- GTTSNKDQDACYLV-UHFFFAOYSA-N Trihydroxybutane Chemical compound CCCC(O)(O)O GTTSNKDQDACYLV-UHFFFAOYSA-N 0.000 claims 1
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 claims 1
- GTVHYMGRLVPCJJ-UHFFFAOYSA-N [3,5-bis(hydroxymethyl)cyclohexyl]methanol Chemical compound OCC1CC(CO)CC(CO)C1 GTVHYMGRLVPCJJ-UHFFFAOYSA-N 0.000 claims 1
- YWMLORGQOFONNT-UHFFFAOYSA-N [3-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=CC(CO)=C1 YWMLORGQOFONNT-UHFFFAOYSA-N 0.000 claims 1
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 claims 1
- 229940074391 gallic acid Drugs 0.000 claims 1
- 235000004515 gallic acid Nutrition 0.000 claims 1
- HXYCHJFUBNTKQR-UHFFFAOYSA-N heptane-1,2,3-triol Chemical compound CCCCC(O)C(O)CO HXYCHJFUBNTKQR-UHFFFAOYSA-N 0.000 claims 1
- SXCBDZAEHILGLM-UHFFFAOYSA-N heptane-1,7-diol Chemical compound OCCCCCCCO SXCBDZAEHILGLM-UHFFFAOYSA-N 0.000 claims 1
- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 claims 1
- XXMIOPMDWAUFGU-UHFFFAOYSA-N hexane-1,6-diol Chemical compound OCCCCCCO XXMIOPMDWAUFGU-UHFFFAOYSA-N 0.000 claims 1
- OHMBHFSEKCCCBW-UHFFFAOYSA-N hexane-2,5-diol Chemical compound CC(O)CCC(C)O OHMBHFSEKCCCBW-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims 1
- NJTGANWAUPEOAX-UHFFFAOYSA-N molport-023-220-454 Chemical compound OCC(O)CO.OCC(O)CO NJTGANWAUPEOAX-UHFFFAOYSA-N 0.000 claims 1
- AEIJTFQOBWATKX-UHFFFAOYSA-N octane-1,2-diol Chemical compound CCCCCCC(O)CO AEIJTFQOBWATKX-UHFFFAOYSA-N 0.000 claims 1
- OEIJHBUUFURJLI-UHFFFAOYSA-N octane-1,8-diol Chemical compound OCCCCCCCCO OEIJHBUUFURJLI-UHFFFAOYSA-N 0.000 claims 1
- GTCCGKPBSJZVRZ-UHFFFAOYSA-N pentane-2,4-diol Chemical compound CC(O)CC(C)O GTCCGKPBSJZVRZ-UHFFFAOYSA-N 0.000 claims 1
- QCDYQQDYXPDABM-UHFFFAOYSA-N phloroglucinol Chemical compound OC1=CC(O)=CC(O)=C1 QCDYQQDYXPDABM-UHFFFAOYSA-N 0.000 claims 1
- NPANDVNCRMZSFT-UHFFFAOYSA-N propane-1,2-diol;propane-1,3-diol Chemical compound CC(O)CO.OCCCO NPANDVNCRMZSFT-UHFFFAOYSA-N 0.000 claims 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 claims 1
- QXJQHYBHAIHNGG-UHFFFAOYSA-N trimethylolethane Chemical compound OCC(C)(CO)CO QXJQHYBHAIHNGG-UHFFFAOYSA-N 0.000 claims 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims 1
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18292809P | 2009-06-01 | 2009-06-01 | |
| US61/182,928 | 2009-06-01 | ||
| PCT/US2010/036923 WO2010141483A2 (en) | 2009-06-01 | 2010-06-01 | Potentiation of autoimmune and inflammatory disease treatments by immune regulatory oligonucleotide (iro) antagonists of tlr7 and tlr9 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012528867A JP2012528867A (ja) | 2012-11-15 |
| JP2012528867A5 true JP2012528867A5 (cg-RX-API-DMAC7.html) | 2017-09-07 |
| JP6275380B2 JP6275380B2 (ja) | 2018-02-07 |
Family
ID=43298446
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012514047A Expired - Fee Related JP6275380B2 (ja) | 2009-06-01 | 2010-06-01 | Ｔｌｒ７およびｔｌｒ９の免疫調節オリゴヌクレオチド（ｉｒｏ）アンタゴニストによる自己免疫および炎症性疾患治療の強化 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8987221B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2437791B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6275380B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN102612561A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2762206C (cg-RX-API-DMAC7.html) |
| ES (1) | ES2624767T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2010141483A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100233270A1 (en) | 2009-01-08 | 2010-09-16 | Northwestern University | Delivery of Oligonucleotide-Functionalized Nanoparticles |
| EP2640420B1 (en) | 2010-11-19 | 2018-08-15 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| US20130096938A1 (en) * | 2011-10-10 | 2013-04-18 | Abbott Biotechnology Ltd. | Managing healthcare services |
| US9539259B2 (en) | 2012-05-23 | 2017-01-10 | The Johns Hopkins University | Compounds and methods of use thereof for treating neurodegenerative disorders |
| AU2012395641B2 (en) | 2012-11-29 | 2019-10-03 | Sbi Biotech Co., Ltd. | Inhibitory oligonucleotide and use thereof |
| CA2896537C (en) * | 2013-01-08 | 2021-10-12 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| EP2754714A1 (en) * | 2013-01-14 | 2014-07-16 | Sarepta Therapeutics, Inc. | Inhibitory oligonucleotides and their use in therapy |
| AU2015349680A1 (en) | 2014-11-21 | 2017-06-08 | Northwestern University | The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
| US20190046638A1 (en) | 2016-04-01 | 2019-02-14 | Checkmate Pharmaceuticals, Inc. | Fc RECEPTOR-MEDIATED DRUG DELIVERY |
| JP7034951B2 (ja) | 2016-06-08 | 2022-03-14 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 操作されたウイルスベクターは炎症および免疫応答の誘導を低減する |
| US11364304B2 (en) | 2016-08-25 | 2022-06-21 | Northwestern University | Crosslinked micellar spherical nucleic acids |
| WO2018209270A1 (en) | 2017-05-11 | 2018-11-15 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (snas) |
| WO2019094548A1 (en) | 2017-11-08 | 2019-05-16 | President And Fellows Of Harvard College | Compositions and methods for inhibiting viral vector-induced inflammatory responses |
| WO2019160866A2 (en) | 2018-02-13 | 2019-08-22 | Checkmate Pharmaceuticals, Inc. | Compositions and methods for tumor immunotherapy |
| AU2019251421B2 (en) | 2018-04-09 | 2025-05-01 | Checkmate Pharmaceuticals | Packaging oligonucleotides into virus-like particles |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5399676A (en) * | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
| US6096722A (en) * | 1990-08-14 | 2000-08-01 | Isis Pharmaceuticals Inc. | Antisense modulation of cell adhesion molecule expression and treatment of cell adhesion molecule-associated diseases |
| US7276489B2 (en) * | 2002-10-24 | 2007-10-02 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends |
| US7973016B2 (en) | 2004-01-23 | 2011-07-05 | Joslin Diebetes Center | Methods of treating, reducing, or preventing autoimmune conditions |
| EA200800943A1 (ru) * | 2005-09-27 | 2008-12-30 | Коли Фармасьютикал Гмбх | Модуляция tlr-опосредуемых иммунных ответов с использованием олигонуклеотидов-адаптеров |
| US8426375B2 (en) * | 2005-10-12 | 2013-04-23 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| CN104278037B (zh) * | 2005-10-12 | 2020-09-15 | 艾德拉药物股份有限公司 | 基于变异应答调制Toll样受体的免疫调节寡核苷酸(IRO)化合物 |
| US8383598B2 (en) * | 2005-10-12 | 2013-02-26 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| PL2154144T3 (pl) | 2008-08-06 | 2015-04-30 | Changchun Huapu Biotechnology Co Ltd | Oligonukleotydy i ich zastosowanie |
-
2010
- 2010-06-01 EP EP10783933.4A patent/EP2437791B1/en not_active Not-in-force
- 2010-06-01 CN CN2010800243380A patent/CN102612561A/zh active Pending
- 2010-06-01 WO PCT/US2010/036923 patent/WO2010141483A2/en not_active Ceased
- 2010-06-01 JP JP2012514047A patent/JP6275380B2/ja not_active Expired - Fee Related
- 2010-06-01 US US12/791,636 patent/US8987221B2/en active Active
- 2010-06-01 ES ES10783933.4T patent/ES2624767T3/es active Active
- 2010-06-01 CA CA2762206A patent/CA2762206C/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2012528867A5 (cg-RX-API-DMAC7.html) | ||
| JP2010536787A5 (cg-RX-API-DMAC7.html) | ||
| JP6406793B2 (ja) | トール様受容体に基づく免疫反応を調整する免疫調節ヌクレオチド（ｉｒｏ）化合物 | |
| JP6275380B2 (ja) | Ｔｌｒ７およびｔｌｒ９の免疫調節オリゴヌクレオチド（ｉｒｏ）アンタゴニストによる自己免疫および炎症性疾患治療の強化 | |
| JP2010536787A (ja) | Ｔｏｌｌ様受容体モジュレータ | |
| JP7478210B2 (ja) | 修飾オリゴヌクレオチド及び使用方法 | |
| JP5813778B2 (ja) | トール様受容体に基づく免疫反応を調節するための免疫調節オリゴヌクレオチド（ｉｒｏ）化合物 | |
| US9828601B2 (en) | Compositions for inhibiting checkpoint gene expression and uses thereof | |
| CA2879066C (en) | Chiral nucleic acid adjuvant | |
| JP5761911B2 (ja) | Ｔｌｒ７およびｔｌｒ８に対する安定化免疫調節ｒｎａ（ｓｉｍｒａ）化合物 | |
| ES2905891T3 (es) | Combinación de oligonucleótidas inmunoestimuladores | |
| JP2013544816A5 (cg-RX-API-DMAC7.html) | ||
| JP2008502688A (ja) | 免疫賦活オリゴヌクレオチドマルチマー | |
| EP2451974A2 (en) | Oligonucleotide-based compounds as inhibitors of toll-like receptors | |
| JP2015532097A5 (cg-RX-API-DMAC7.html) | ||
| KR101898177B1 (ko) | 톨－유사 수용체 기반 면역 반응을 조절하기 위한 면역 조절 올리고누클레오티드 （ｉｒｏ） 화합물 | |
| JP2017528129A (ja) | 異常なレベル及び／又は活性のｉｆｐ３５ファミリーのタンパク質に関連する疾患又は障害を治療及び／又は予防するための方法及び組成物 | |
| JP2022010100A (ja) | Ｈｉｖの治療のための手段 | |
| JP2011515357A5 (cg-RX-API-DMAC7.html) | ||
| US20170009230A1 (en) | Compositions for inhibiting dux4 gene expression and uses thereof | |
| JP2020521491A5 (cg-RX-API-DMAC7.html) | ||
| Kandimalla et al. | Modulation of endosomal Toll-like receptor-mediated immune responses by synthetic oligonucleotides | |
| CN112840026B (zh) | 抑制tigit基因表达的组合物和方法 |