JP2019518778A5 - - Google Patents

Info

Publication number

JP2019518778A5

JP2019518778A5 JP2018567264A JP2018567264A JP2019518778A5 JP 2019518778 A5 JP2019518778 A5 JP 2019518778A5 JP 2018567264 A JP2018567264 A JP 2018567264A JP 2018567264 A JP2018567264 A JP 2018567264A JP 2019518778 A5 JP2019518778 A5 JP 2019518778A5

Authority

JP

Japan

Prior art keywords

formula

compound

process according

agent

steps

Prior art date

2017-06-22

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

• Espacenet
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• 150000001875 compounds Chemical class 0.000 claims description 82
• 238000000034 method Methods 0.000 claims description 64
• 239000003795 chemical substances by application Substances 0.000 claims description 40
• 108091034117 Oligonucleotide Proteins 0.000 claims description 35
• 125000003545 alkoxy group Chemical group 0.000 claims description 20
• 239000002773 nucleotide Substances 0.000 claims description 20
• 125000003729 nucleotide group Chemical group 0.000 claims description 20
• 239000000074 antisense oligonucleotide Substances 0.000 claims description 16
• 238000012230 antisense oligonucleotides Methods 0.000 claims description 16
• 150000003839 salts Chemical class 0.000 claims description 16
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 8
• 125000000217 alkyl group Chemical group 0.000 claims description 8
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 8
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 8
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 8
• 239000006227 byproduct Substances 0.000 claims description 6
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
• 125000006239 protecting group Chemical group 0.000 claims description 6
• 239000007787 solid Substances 0.000 claims description 6
• 239000003153 chemical reaction reagent Substances 0.000 claims description 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
• JUDOLRSMWHVKGX-UHFFFAOYSA-N 1,1-dioxo-1$l^{6},2-benzodithiol-3-one Chemical group C1=CC=C2C(=O)SS(=O)(=O)C2=C1 JUDOLRSMWHVKGX-UHFFFAOYSA-N 0.000 claims description 4
• GVZJRBAUSGYWJI-UHFFFAOYSA-N 2,5-bis(3-dodecylthiophen-2-yl)thiophene Chemical compound C1=CSC(C=2SC(=CC=2)C2=C(C=CS2)CCCCCCCCCCCC)=C1CCCCCCCCCCCC GVZJRBAUSGYWJI-UHFFFAOYSA-N 0.000 claims description 4
• FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 claims description 4
• OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 claims description 4
• RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 claims description 4
• LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 4
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 4
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 4
• 229930024421 Adenine Natural products 0.000 claims description 4
• 229960000643 adenine Drugs 0.000 claims description 4
• 229940104302 cytosine Drugs 0.000 claims description 4
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• IXGZXXBJSZISOO-UHFFFAOYSA-N s-(2-phenylacetyl)sulfanyl 2-phenylethanethioate Chemical group C=1C=CC=CC=1CC(=O)SSC(=O)CC1=CC=CC=C1 IXGZXXBJSZISOO-UHFFFAOYSA-N 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 229940113082 thymine Drugs 0.000 claims description 4
• 229940035893 uracil Drugs 0.000 claims description 4
• 238000004064 recycling Methods 0.000 claims description 3
• 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• YWZHEXZIISFIDA-UHFFFAOYSA-N 5-amino-1,2,4-dithiazole-3-thione Chemical group NC1=NC(=S)SS1 YWZHEXZIISFIDA-UHFFFAOYSA-N 0.000 claims description 2
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000006242 amine protecting group Chemical group 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 239000007800 oxidant agent Substances 0.000 claims description 2
• 238000005987 sulfurization reaction Methods 0.000 claims description 2
• 229940075420 xanthine Drugs 0.000 claims description 2
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims 2
• 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 230000003134 recirculating effect Effects 0.000 claims 1
• 238000006467 substitution reaction Methods 0.000 claims 1
• 0 **OC1[C@@](*)(CO*)OC2(*)C1C2* Chemical compound **OC1[C@@](*)(CO*)OC2(*)C1C2* 0.000 description 1
• MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical group C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• IIFWTJATQRKFCB-UHFFFAOYSA-N CCC(c(cccc1)c1N=O)=O Chemical compound CCC(c(cccc1)c1N=O)=O IIFWTJATQRKFCB-UHFFFAOYSA-N 0.000 description 1