DK2788487T3 - Oligonucleotide Analogs Targeted against HUMAN LMNA - Google Patents

Info

Publication number

DK2788487T3

DK2788487T3 DK12805882.3T DK12805882T DK2788487T3 DK 2788487 T3 DK2788487 T3 DK 2788487T3 DK 12805882 T DK12805882 T DK 12805882T DK 2788487 T3 DK2788487 T3 DK 2788487T3

Authority

DK

Denmark

Prior art keywords

alkyl

occurrence

independently

oligonucleotide

bond

Prior art date

2011-12-08

Links

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• 101001003584 Homo sapiens Prelamin-A/C Proteins 0.000 title claims abstract description 14
• 102100026531 Prelamin-A/C Human genes 0.000 title claims abstract description 5
• 108091034117 Oligonucleotide Proteins 0.000 title claims description 111
• 239000000074 antisense oligonucleotide Substances 0.000 claims abstract description 45
• 238000012230 antisense oligonucleotides Methods 0.000 claims abstract description 45
• 108020004999 messenger RNA Proteins 0.000 claims abstract description 38
• 125000000217 alkyl group Chemical group 0.000 claims description 195
• 229910052739 hydrogen Inorganic materials 0.000 claims description 120
• 239000001257 hydrogen Substances 0.000 claims description 120
• 230000008685 targeting Effects 0.000 claims description 92
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 67
• 125000000623 heterocyclic group Chemical group 0.000 claims description 60
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 55
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
• 125000003545 alkoxy group Chemical group 0.000 claims description 53
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 53
• 125000003118 aryl group Chemical group 0.000 claims description 48
• 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims description 41
• 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims description 41
• 125000005647 linker group Chemical group 0.000 claims description 40
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 35
• SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 claims description 34
• 125000001072 heteroaryl group Chemical group 0.000 claims description 31
• 150000007523 nucleic acids Chemical class 0.000 claims description 31
• 235000001014 amino acid Nutrition 0.000 claims description 30
• 102000039446 nucleic acids Human genes 0.000 claims description 28
• 108020004707 nucleic acids Proteins 0.000 claims description 28
• 150000001413 amino acids Chemical class 0.000 claims description 27
• 229910052760 oxygen Inorganic materials 0.000 claims description 27
• 229910052799 carbon Inorganic materials 0.000 claims description 23
• 229960002684 aminocaproic acid Drugs 0.000 claims description 21
• UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 21
• 229910052717 sulfur Inorganic materials 0.000 claims description 20
• 125000004429 atom Chemical group 0.000 claims description 18
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 17
• 125000003282 alkyl amino group Chemical group 0.000 claims description 16
• 125000000747 amidyl group Chemical group [H][N-]* 0.000 claims description 16
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 12
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
• 239000004471 Glycine Substances 0.000 claims description 11
• 229940000635 beta-alanine Drugs 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• 229940099352 cholate Drugs 0.000 claims description 9
• BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims description 9
• 229940009976 deoxycholate Drugs 0.000 claims description 9
• KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims description 9
• 125000004043 oxo group Chemical group O=* 0.000 claims description 9
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 8
• 150000003839 salts Chemical class 0.000 claims description 8
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 7
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 7
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
• 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 6
• 125000002950 monocyclic group Chemical group 0.000 claims description 6
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 5
• MHCMWGPPLOSCJY-UHFFFAOYSA-N 4-$l^{1}-azanylmorpholine Chemical compound [N]N1CCOCC1 MHCMWGPPLOSCJY-UHFFFAOYSA-N 0.000 claims description 4
• 239000004215 Carbon black (E152) Substances 0.000 claims description 4
• 235000018417 cysteine Nutrition 0.000 claims description 4
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 4
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 4
• 229930195733 hydrocarbon Natural products 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 150000002430 hydrocarbons Chemical class 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 6
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
• 108020000948 Antisense Oligonucleotides Proteins 0.000 abstract description 28
• 102000001708 Protein Isoforms Human genes 0.000 abstract description 3
• 108010029485 Protein Isoforms Proteins 0.000 abstract description 3
• -1 guanidinyl Chemical group 0.000 description 109
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 65
• 208000025500 Hutchinson-Gilford progeria syndrome Diseases 0.000 description 58
• 102000008201 Lamin Type A Human genes 0.000 description 58
• 108010021099 Lamin Type A Proteins 0.000 description 58
• 208000007932 Progeria Diseases 0.000 description 56
• 108020004414 DNA Proteins 0.000 description 54
• 230000000692 anti-sense effect Effects 0.000 description 52
• 230000000295 complement effect Effects 0.000 description 50
• 210000004027 cell Anatomy 0.000 description 41
• 125000002091 cationic group Chemical group 0.000 description 40
• 108090000765 processed proteins & peptides Proteins 0.000 description 40
• 150000001875 compounds Chemical class 0.000 description 32
• 150000003254 radicals Chemical class 0.000 description 28
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
• 108010078791 Carrier Proteins Proteins 0.000 description 23
• 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 description 23
• 125000002947 alkylene group Chemical group 0.000 description 22
• 125000003710 aryl alkyl group Chemical group 0.000 description 22
• 230000032258 transport Effects 0.000 description 21
• 108010068380 arginylarginine Proteins 0.000 description 20
• 229910052757 nitrogen Inorganic materials 0.000 description 20
• 125000004432 carbon atom Chemical group C* 0.000 description 19
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
• 238000000034 method Methods 0.000 description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 18
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 16
• 229910052698 phosphorus Inorganic materials 0.000 description 16
• 239000011574 phosphorus Substances 0.000 description 16
• 108091033319 polynucleotide Proteins 0.000 description 16
• 102000040430 polynucleotide Human genes 0.000 description 16
• 239000002157 polynucleotide Substances 0.000 description 16
• 108020005067 RNA Splice Sites Proteins 0.000 description 15
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 15
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 15
• 239000000203 mixture Substances 0.000 description 15
• 239000002773 nucleotide Substances 0.000 description 15
• 239000004475 Arginine Substances 0.000 description 14
• 101710163270 Nuclease Proteins 0.000 description 14
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 14
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 14
• 239000003795 chemical substances by application Substances 0.000 description 14
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
• 125000003729 nucleotide group Chemical group 0.000 description 14
• 239000001301 oxygen Substances 0.000 description 14
• 125000005843 halogen group Chemical group 0.000 description 13
• 102000004196 processed proteins & peptides Human genes 0.000 description 13
• 108090000623 proteins and genes Proteins 0.000 description 13
• 125000005129 aryl carbonyl group Chemical group 0.000 description 12
• 125000001424 substituent group Chemical group 0.000 description 12
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 11
• 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 11
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 11
• 150000005840 aryl radicals Chemical class 0.000 description 11
• 230000027455 binding Effects 0.000 description 11
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 description 11
• 125000005170 cycloalkyloxycarbonyl group Chemical group 0.000 description 11
• 230000000694 effects Effects 0.000 description 11
• OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 description 10
• 108091027305 Heteroduplex Proteins 0.000 description 10
• 108091093037 Peptide nucleic acid Proteins 0.000 description 10
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 10
• 125000004122 cyclic group Chemical group 0.000 description 10
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 10
• ANCLJVISBRWUTR-UHFFFAOYSA-N diaminophosphinic acid Chemical compound NP(N)(O)=O ANCLJVISBRWUTR-UHFFFAOYSA-N 0.000 description 10
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
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• 102000057754 human LMNA Human genes 0.000 description 9
• 238000009396 hybridization Methods 0.000 description 9
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• 238000004458 analytical method Methods 0.000 description 8
• 238000002474 experimental method Methods 0.000 description 8
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• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 7
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• 210000004962 mammalian cell Anatomy 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 230000004048 modification Effects 0.000 description 7
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• 125000004433 nitrogen atom Chemical group N* 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• 235000013930 proline Nutrition 0.000 description 7
• 239000011593 sulfur Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 238000011282 treatment Methods 0.000 description 7
• 238000011144 upstream manufacturing Methods 0.000 description 7
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• 230000001594 aberrant effect Effects 0.000 description 6
• 230000001413 cellular effect Effects 0.000 description 6
• 150000003983 crown ethers Chemical group 0.000 description 6
• 125000000753 cycloalkyl group Chemical group 0.000 description 6
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 6
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
• 235000018102 proteins Nutrition 0.000 description 6
• 102000004169 proteins and genes Human genes 0.000 description 6
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 6
• QVVDVENEPNODSI-BTNSXGMBSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylidene Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QVVDVENEPNODSI-BTNSXGMBSA-N 0.000 description 5
• 125000000923 (C1-C30) alkyl group Chemical group 0.000 description 5
• 229930024421 Adenine Natural products 0.000 description 5
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 5
• 229960000643 adenine Drugs 0.000 description 5
• 230000015556 catabolic process Effects 0.000 description 5
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 5
• 229940104302 cytosine Drugs 0.000 description 5
• 238000006731 degradation reaction Methods 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
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• 125000004430 oxygen atom Chemical group O* 0.000 description 5
• 125000003386 piperidinyl group Chemical group 0.000 description 5
• 229940035893 uracil Drugs 0.000 description 5
• XPSGESXVBSQZPL-SRVKXCTJSA-N Arg-Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XPSGESXVBSQZPL-SRVKXCTJSA-N 0.000 description 4
• HQIZDMIGUJOSNI-IUCAKERBSA-N Arg-Gly-Arg Chemical compound N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O HQIZDMIGUJOSNI-IUCAKERBSA-N 0.000 description 4
• 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
• 108091028043 Nucleic acid sequence Proteins 0.000 description 4
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• 125000000539 amino acid group Chemical group 0.000 description 4
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• 125000002619 bicyclic group Chemical group 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• 238000003776 cleavage reaction Methods 0.000 description 4
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• 125000001188 haloalkyl group Chemical group 0.000 description 4
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
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• 125000004076 pyridyl group Chemical group 0.000 description 4
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• 238000011160 research Methods 0.000 description 4
• 229920006395 saturated elastomer Polymers 0.000 description 4
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• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 4
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
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• 230000009471 action Effects 0.000 description 3
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• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
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