JP4417728B2 - Pna単量体および前駆体 - Google Patents
Pna単量体および前駆体 Download PDFInfo
- Publication number
- JP4417728B2 JP4417728B2 JP2003587791A JP2003587791A JP4417728B2 JP 4417728 B2 JP4417728 B2 JP 4417728B2 JP 2003587791 A JP2003587791 A JP 2003587791A JP 2003587791 A JP2003587791 A JP 2003587791A JP 4417728 B2 JP4417728 B2 JP 4417728B2
- Authority
- JP
- Japan
- Prior art keywords
- pyrimidine
- amino
- formula
- compound
- alkyl
- 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
- 239000000178 monomer Substances 0.000 title abstract description 85
- 239000002243 precursor Substances 0.000 title description 11
- 238000000034 method Methods 0.000 claims abstract description 168
- 125000006239 protecting group Chemical group 0.000 claims abstract description 42
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 38
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 36
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 36
- 239000011593 sulfur Substances 0.000 claims abstract description 36
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 35
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 31
- 239000002253 acid Substances 0.000 claims abstract description 29
- 238000002360 preparation method Methods 0.000 claims abstract description 28
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 20
- 150000002367 halogens Chemical class 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910052760 oxygen Chemical group 0.000 claims abstract description 17
- 239000001301 oxygen Chemical group 0.000 claims abstract description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 13
- 150000002825 nitriles Chemical class 0.000 claims abstract description 12
- -1 phenyl halide Chemical class 0.000 claims description 192
- 150000001875 compounds Chemical class 0.000 claims description 167
- 238000005859 coupling reaction Methods 0.000 claims description 52
- 239000003153 chemical reaction reagent Substances 0.000 claims description 36
- 230000008878 coupling Effects 0.000 claims description 36
- 238000010168 coupling process Methods 0.000 claims description 36
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 29
- 150000007530 organic bases Chemical class 0.000 claims description 29
- 230000000269 nucleophilic effect Effects 0.000 claims description 25
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 23
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 20
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 16
- 238000010647 peptide synthesis reaction Methods 0.000 claims description 16
- 238000007363 ring formation reaction Methods 0.000 claims description 15
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 14
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 13
- 238000010511 deprotection reaction Methods 0.000 claims description 13
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 11
- 125000000524 functional group Chemical group 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 229930024421 Adenine Natural products 0.000 claims description 10
- 229960000643 adenine Drugs 0.000 claims description 10
- 150000008064 anhydrides Chemical class 0.000 claims description 10
- 229940104302 cytosine Drugs 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 229940113082 thymine Drugs 0.000 claims description 9
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 8
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical class NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 claims description 6
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 3
- 229940045145 uridine Drugs 0.000 claims description 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical group 0.000 claims description 2
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 claims 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 4
- PTFYZDMJTFMPQW-UHFFFAOYSA-N 1,10-dihydropyrimido[5,4-b][1,4]benzoxazin-2-one Chemical compound O1C2=CC=CC=C2N=C2C1=CNC(=O)N2 PTFYZDMJTFMPQW-UHFFFAOYSA-N 0.000 claims 2
- FBMZEITWVNHWJW-UHFFFAOYSA-N 1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound OC1=NC=NC2=C1C=CN2 FBMZEITWVNHWJW-UHFFFAOYSA-N 0.000 claims 2
- HTDPDLVWFWOIBZ-UHFFFAOYSA-N 1,7-dihydropyrrolo[2,3-d]pyrimidine-4-thione Chemical compound SC1=NC=NC2=C1C=CN2 HTDPDLVWFWOIBZ-UHFFFAOYSA-N 0.000 claims 2
- KZRAKSCBDFIHPR-UHFFFAOYSA-N 1,8-dihydropyrido[2,3-d]pyrimidine-2,7-dione Chemical compound C1=CC(=O)NC2=NC(O)=NC=C21 KZRAKSCBDFIHPR-UHFFFAOYSA-N 0.000 claims 2
- ZBTXKBZHCXRWNZ-UHFFFAOYSA-N 1,9-dihydropyrimido[4,5-b]indol-2-one Chemical compound C12=CC=CC=C2NC2=C1C=NC(=O)N2 ZBTXKBZHCXRWNZ-UHFFFAOYSA-N 0.000 claims 2
- JAFSZKZHCNWJIY-UHFFFAOYSA-N 1-methyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1C=NC(=O)C2=C1C=NN2C JAFSZKZHCNWJIY-UHFFFAOYSA-N 0.000 claims 2
- WFQKKZBONXZYLH-UHFFFAOYSA-N 1-methylpyrazolo[4,3-d]pyrimidin-7-amine Chemical compound C1=NC(N)=C2N(C)N=CC2=N1 WFQKKZBONXZYLH-UHFFFAOYSA-N 0.000 claims 2
- ZHZOKCCYJUETEO-UHFFFAOYSA-N 1-methylpyrazolo[4,3-d]pyrimidine-5,7-diamine Chemical compound NC1=NC(N)=C2N(C)N=CC2=N1 ZHZOKCCYJUETEO-UHFFFAOYSA-N 0.000 claims 2
- DSHFJEVKQFFWHK-UHFFFAOYSA-N 1-prop-1-ynylpyrimidine-2,4-dione Chemical compound CC#CN1C=CC(=O)NC1=O DSHFJEVKQFFWHK-UHFFFAOYSA-N 0.000 claims 2
- GEWRKGDRYZIFNP-UHFFFAOYSA-N 1h-1,3,5-triazine-2,4-dione Chemical compound OC1=NC=NC(O)=N1 GEWRKGDRYZIFNP-UHFFFAOYSA-N 0.000 claims 2
- ZBNZAJFNDPPMDT-UHFFFAOYSA-N 1h-imidazole-5-carboxamide Chemical compound NC(=O)C1=CNC=N1 ZBNZAJFNDPPMDT-UHFFFAOYSA-N 0.000 claims 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims 2
- RGKLWAHLGYLIKT-UHFFFAOYSA-N 2,3-dihydrotriazolo[4,5-d]pyrimidine-7-thione Chemical compound S=C1N=CN=C2NNN=C12 RGKLWAHLGYLIKT-UHFFFAOYSA-N 0.000 claims 2
- JOGOXDMLVHWTMG-UHFFFAOYSA-N 2-amino-1,7-dihydropyrrolo[2,3-d]pyrimidine-4-thione Chemical compound S=C1NC(N)=NC2=C1C=CN2 JOGOXDMLVHWTMG-UHFFFAOYSA-N 0.000 claims 2
- NINMLCLBRADCOF-UHFFFAOYSA-N 2-amino-1-methylpyrimidin-4-one Chemical compound CN1C=CC(=O)N=C1N NINMLCLBRADCOF-UHFFFAOYSA-N 0.000 claims 2
- NIVFVAZIYOKLCC-UHFFFAOYSA-N 4-prop-1-ynyl-2h-isoquinolin-1-one Chemical compound C1=CC=C2C(C#CC)=CNC(=O)C2=C1 NIVFVAZIYOKLCC-UHFFFAOYSA-N 0.000 claims 2
- GNGUIFCJLKENCH-UHFFFAOYSA-N 5-amino-2,3-dihydrotriazolo[4,5-d]pyrimidine-7-thione Chemical compound S=C1N=C(N)N=C2NNN=C21 GNGUIFCJLKENCH-UHFFFAOYSA-N 0.000 claims 2
- SVXNJCYYMRMXNM-UHFFFAOYSA-N 5-amino-2h-1,2,4-triazin-3-one Chemical compound NC=1C=NNC(=O)N=1 SVXNJCYYMRMXNM-UHFFFAOYSA-N 0.000 claims 2
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims 2
- ZFTBZKVVGZNMJR-UHFFFAOYSA-N 5-chlorouracil Chemical compound ClC1=CNC(=O)NC1=O ZFTBZKVVGZNMJR-UHFFFAOYSA-N 0.000 claims 2
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 claims 2
- SHLJOANTPJWIHS-UHFFFAOYSA-N 5-methyl-1h-pyrimidin-6-one Chemical compound CC1=CN=CNC1=O SHLJOANTPJWIHS-UHFFFAOYSA-N 0.000 claims 2
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 2
- OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 claims 2
- VYDWQPKRHOGLPA-UHFFFAOYSA-N 5-nitroimidazole Chemical compound [O-][N+](=O)C1=CN=CN1 VYDWQPKRHOGLPA-UHFFFAOYSA-N 0.000 claims 2
- BZUZJVLPAKJIBP-UHFFFAOYSA-N 6-amino-1,2-dihydropyrazolo[3,4-d]pyrimidin-4-one Chemical compound O=C1N=C(N)N=C2NNC=C21 BZUZJVLPAKJIBP-UHFFFAOYSA-N 0.000 claims 2
- CEQNENJYRNPLPQ-UHFFFAOYSA-N 6-amino-1,2-dihydropyrazolo[3,4-d]pyrimidine-4-thione Chemical compound S=C1N=C(N)N=C2NNC=C21 CEQNENJYRNPLPQ-UHFFFAOYSA-N 0.000 claims 2
- SSPYSWLZOPCOLO-UHFFFAOYSA-N 6-azauracil Chemical compound O=C1C=NNC(=O)N1 SSPYSWLZOPCOLO-UHFFFAOYSA-N 0.000 claims 2
- BLYYQDFZPGAAQM-UHFFFAOYSA-N 6-methoxy-1h-pyrimidin-2-one Chemical compound COC1=CC=NC(O)=N1 BLYYQDFZPGAAQM-UHFFFAOYSA-N 0.000 claims 2
- AVBPTIYKXNVKNJ-UHFFFAOYSA-N 6-methyl-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C=2C1=CC(C)=CC=2 AVBPTIYKXNVKNJ-UHFFFAOYSA-N 0.000 claims 2
- HRYKDUPGBWLLHO-UHFFFAOYSA-N 8-azaadenine Chemical compound NC1=NC=NC2=NNN=C12 HRYKDUPGBWLLHO-UHFFFAOYSA-N 0.000 claims 2
- OEEYCNOOAHGFHL-UHFFFAOYSA-N 8-azahypoxanthine Chemical compound O=C1N=CN=C2NNN=C12 OEEYCNOOAHGFHL-UHFFFAOYSA-N 0.000 claims 2
- WXJVQHWAFBGNLS-UHFFFAOYSA-N 8-methyl-2h-isoquinolin-1-one Chemical compound C1=NC(O)=C2C(C)=CC=CC2=C1 WXJVQHWAFBGNLS-UHFFFAOYSA-N 0.000 claims 2
- MJJDPSZRCPHHFO-UHFFFAOYSA-N CN1N=CC=2N=CNC(C21)=S Chemical compound CN1N=CC=2N=CNC(C21)=S MJJDPSZRCPHHFO-UHFFFAOYSA-N 0.000 claims 2
- OLAFFPNXVJANFR-UHFFFAOYSA-N DG Chemical compound N1C(N)=NC(=O)C2=C1NC=C2 OLAFFPNXVJANFR-UHFFFAOYSA-N 0.000 claims 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 2
- XUBOOEPACDFUBU-UHFFFAOYSA-N NC1=C2N(C(NC2N=CN1)=O)C Chemical compound NC1=C2N(C(NC2N=CN1)=O)C XUBOOEPACDFUBU-UHFFFAOYSA-N 0.000 claims 2
- ZHSSTJKANFCVAA-UHFFFAOYSA-N NC=1NC(C2=C(N1)C=NN2C)=O Chemical compound NC=1NC(C2=C(N1)C=NN2C)=O ZHSSTJKANFCVAA-UHFFFAOYSA-N 0.000 claims 2
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 claims 2
- WIJLJNRYFCNFTD-UHFFFAOYSA-N chembl3273108 Chemical compound O=C1NC(=O)NC=C1C1=NC=CN1 WIJLJNRYFCNFTD-UHFFFAOYSA-N 0.000 claims 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims 2
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims 2
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims 2
- PYAOPMWCFSVFOT-UHFFFAOYSA-N tisopurine Chemical compound SC1=NC=NC2=C1C=NN2 PYAOPMWCFSVFOT-UHFFFAOYSA-N 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 58
- 238000003786 synthesis reaction Methods 0.000 abstract description 58
- 108091093037 Peptide nucleic acid Proteins 0.000 abstract description 5
- 150000007513 acids Chemical class 0.000 abstract description 5
- 150000003573 thiols Chemical class 0.000 abstract description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 78
- 238000006243 chemical reaction Methods 0.000 description 68
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 31
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 27
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 21
- LREXRKBIOMBDFW-UHFFFAOYSA-N 1-(1,3-benzothiazol-2-ylsulfonyl)piperazin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1CNCCN1S(=O)(=O)C1=NC2=CC=CC=C2S1 LREXRKBIOMBDFW-UHFFFAOYSA-N 0.000 description 19
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000004471 Glycine Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 0 C*c1c(COC(Nc2c3nc[n](CC(O)O)c3ncn2)=O)c(*)c2OC(*)(*)Oc2c1* Chemical compound C*c1c(COC(Nc2c3nc[n](CC(O)O)c3ncn2)=O)c(*)c2OC(*)(*)Oc2c1* 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 108020004414 DNA Proteins 0.000 description 15
- QSNHRCZHENQCLL-UHFFFAOYSA-N ethyl 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethylamino]acetate Chemical compound C1=CC=C2SC(S(=O)(=O)NCCNCC(=O)OCC)=NC2=C1 QSNHRCZHENQCLL-UHFFFAOYSA-N 0.000 description 15
- 230000004913 activation Effects 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 14
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
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- FSCFFGNXMFCNDM-JTQLQIEISA-N ethyl (2s)-2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethylamino]propanoate Chemical compound C1=CC=C2SC(S(=O)(=O)NCCN[C@@H](C)C(=O)OCC)=NC2=C1 FSCFFGNXMFCNDM-JTQLQIEISA-N 0.000 description 1
- HTJYWHZUOCYJBL-UHFFFAOYSA-N ethyl 2-(2-amino-6-iodopurin-9-yl)acetate Chemical compound N1=C(N)N=C2N(CC(=O)OCC)C=NC2=C1I HTJYWHZUOCYJBL-UHFFFAOYSA-N 0.000 description 1
- MCOVDURKZQNFBE-UHFFFAOYSA-N ethyl 2-(6-aminopurin-9-yl)acetate Chemical compound N1=CN=C2N(CC(=O)OCC)C=NC2=C1N MCOVDURKZQNFBE-UHFFFAOYSA-N 0.000 description 1
- UKTHTMWCROCXPP-UHFFFAOYSA-N ethyl 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethyl-[2-[2-[(3,4-dimethoxyphenyl)methoxycarbonylamino]-6-oxo-3h-purin-9-yl]acetyl]amino]acetate Chemical compound N=1C2=CC=CC=C2SC=1S(=O)(=O)NCCN(CC(=O)OCC)C(=O)CN1C=NC(C(N2)=O)=C1N=C2NC(=O)OCC1=CC=C(OC)C(OC)=C1 UKTHTMWCROCXPP-UHFFFAOYSA-N 0.000 description 1
- MCZKZSKVXMXSDE-UHFFFAOYSA-N ethyl 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethyl-[2-[2-[(4-methoxyphenyl)methoxycarbonylamino]-6-oxo-3h-purin-9-yl]acetyl]amino]acetate Chemical compound N=1C2=CC=CC=C2SC=1S(=O)(=O)NCCN(CC(=O)OCC)C(=O)CN1C=NC(C(N2)=O)=C1N=C2NC(=O)OCC1=CC=C(OC)C=C1 MCZKZSKVXMXSDE-UHFFFAOYSA-N 0.000 description 1
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- UKUQOIXNVWVABY-UHFFFAOYSA-N ethyl 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethyl-[2-[4-[(4-methoxyphenyl)methoxycarbonylamino]-2-oxopyrimidin-1-yl]acetyl]amino]acetate Chemical compound N=1C2=CC=CC=C2SC=1S(=O)(=O)NCCN(CC(=O)OCC)C(=O)CN(C(N=1)=O)C=CC=1NC(=O)OCC1=CC=C(OC)C=C1 UKUQOIXNVWVABY-UHFFFAOYSA-N 0.000 description 1
- VFKDKDGQFCPHNU-UHFFFAOYSA-N ethyl 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethyl-[2-[6-[(3,4-dimethoxyphenyl)methoxycarbonylamino]purin-9-yl]acetyl]amino]acetate Chemical compound N=1C2=CC=CC=C2SC=1S(=O)(=O)NCCN(CC(=O)OCC)C(=O)CN(C1=NC=N2)C=NC1=C2NC(=O)OCC1=CC=C(OC)C(OC)=C1 VFKDKDGQFCPHNU-UHFFFAOYSA-N 0.000 description 1
- YHUMIPIGIAHNTB-UHFFFAOYSA-N ethyl 2-[2-[(4-chloro-5-methoxy-1,3-benzothiazol-2-yl)sulfonylamino]ethylamino]acetate Chemical compound COC1=CC=C2SC(S(=O)(=O)NCCNCC(=O)OCC)=NC2=C1Cl YHUMIPIGIAHNTB-UHFFFAOYSA-N 0.000 description 1
- BUAVGTPZPCARMY-UHFFFAOYSA-N ethyl 2-[2-[(5-chloro-1,3-benzothiazol-2-yl)sulfonylamino]ethylamino]acetate Chemical compound ClC1=CC=C2SC(S(=O)(=O)NCCNCC(=O)OCC)=NC2=C1 BUAVGTPZPCARMY-UHFFFAOYSA-N 0.000 description 1
- OBPSXYNYSJXOIK-UHFFFAOYSA-N ethyl 2-[4-(1,3-benzodioxol-5-ylmethoxycarbonylamino)-2-oxopyrimidin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C=CC(NC(=O)OCC=2C=C3OCOC3=CC=2)=N1 OBPSXYNYSJXOIK-UHFFFAOYSA-N 0.000 description 1
- QTLAWKXFBSKFDT-UHFFFAOYSA-N ethyl 2-[6-(1,3-benzodioxol-5-ylmethoxycarbonylamino)purin-9-yl]acetate Chemical compound C1=C2OCOC2=CC(COC(=O)NC2=C3N=CN(C3=NC=N2)CC(=O)OCC)=C1 QTLAWKXFBSKFDT-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
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- LDTLDBDUBGAEDT-UHFFFAOYSA-N methyl 3-sulfanylpropanoate Chemical compound COC(=O)CCS LDTLDBDUBGAEDT-UHFFFAOYSA-N 0.000 description 1
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- 238000006384 oligomerization reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
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- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- RHDXSLLGPJSSGW-VEGRVEBRSA-N phosphoric acid;(2r,3r,4r)-2,3,4,5-tetrahydroxypentanal Chemical group OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@@H](O)C=O RHDXSLLGPJSSGW-VEGRVEBRSA-N 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
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- 238000012545 processing Methods 0.000 description 1
- QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
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- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
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- 150000003839 salts Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
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- 230000009870 specific binding Effects 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
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- 230000009897 systematic effect Effects 0.000 description 1
- QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/70—Sulfur atoms
- C07D277/76—Sulfur atoms attached to a second hetero atom
- C07D277/80—Sulfur atoms attached to a second hetero atom to a nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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KR1020020023157A KR20030084444A (ko) | 2002-04-26 | 2002-04-26 | Pna 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
PCT/IB2003/001595 WO2003091231A1 (en) | 2002-04-26 | 2003-04-28 | Pna monomer and precursor |
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JP2009006471A Division JP4927105B2 (ja) | 2002-04-26 | 2009-01-15 | Pna単量体および前駆体 |
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JP2003587791A Expired - Lifetime JP4417728B2 (ja) | 2002-04-26 | 2003-04-28 | Pna単量体および前駆体 |
JP2009006471A Expired - Lifetime JP4927105B2 (ja) | 2002-04-26 | 2009-01-15 | Pna単量体および前駆体 |
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---|---|---|---|---|
KR100464261B1 (ko) * | 2002-01-24 | 2005-01-03 | 주식회사 파나진 | Pna 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
US7211668B2 (en) | 2003-07-28 | 2007-05-01 | Panagene, Inc. | PNA monomer and precursor |
US20050261347A1 (en) * | 2003-10-24 | 2005-11-24 | Wyeth | Dihydrobenzofuranyl alkanamine derivatives and methods for using same |
US7435837B2 (en) * | 2003-10-24 | 2008-10-14 | Wyeth | Dihydrobenzofuranyl alkanamine derivatives and methods for using same |
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EP2236616B1 (en) | 2005-06-02 | 2013-12-18 | AdvanDx, Inc. | Peptide nucleic acid probes for analysis of microorganisms |
WO2009032901A1 (en) * | 2007-09-04 | 2009-03-12 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Biosensors and related methods |
CA2764158A1 (en) | 2009-06-01 | 2010-12-09 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
KR101944119B1 (ko) | 2009-11-13 | 2019-01-30 | 사렙타 쎄러퓨틱스 인코퍼레이티드 | 안티센스 항바이러스 화합물 및 인플루엔자 바이러스 감염을 치료하는 방법 |
WO2011064552A1 (en) | 2009-11-30 | 2011-06-03 | Isis Innovation Limited | Conjugates for delivery of biologically active compounds |
WO2011112516A1 (en) | 2010-03-08 | 2011-09-15 | Ico Therapeutics Inc. | Treating and preventing hepatitis c virus infection using c-raf kinase antisense oligonucleotides |
WO2011113015A2 (en) | 2010-03-12 | 2011-09-15 | Avi Biopharma, Inc. | Antisense modulation of nuclear hormone receptors |
AU2011248625B2 (en) | 2010-04-26 | 2017-01-05 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-tRNA synthetase |
EP2563381B1 (en) | 2010-04-27 | 2017-08-09 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of isoleucyl trna synthetases |
CN103097524B (zh) | 2010-04-28 | 2016-08-03 | Atyr医药公司 | 与丙氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现 |
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AU2011248490B2 (en) | 2010-04-29 | 2016-11-10 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Asparaginyl tRNA synthetases |
CN103096925A (zh) | 2010-05-03 | 2013-05-08 | Atyr医药公司 | 与精氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现 |
WO2011140132A2 (en) | 2010-05-03 | 2011-11-10 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-alpha-trna synthetases |
ES2668207T3 (es) | 2010-05-03 | 2018-05-17 | Atyr Pharma, Inc. | Descubrimiento innovador de composiciones terapéuticas, de diagnóstico y de anticuerpos relacionadas con fragmentos de proteínas de metionil-ARNt sintetasas |
US9062302B2 (en) | 2010-05-04 | 2015-06-23 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of p38 multi-tRNA synthetase complex |
CA3090304A1 (en) | 2010-05-13 | 2011-11-17 | Sarepta Therapeutics, Inc. | Antisense modulation of interleukins 17 and 23 signaling |
CN103200953B (zh) | 2010-05-14 | 2017-02-15 | Atyr 医药公司 | 与苯丙氨酰‑β‑tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现 |
CN103096914B (zh) | 2010-05-17 | 2015-08-12 | Atyr医药公司 | 与亮氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现 |
AU2011258106B2 (en) | 2010-05-27 | 2017-02-23 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-tRNA synthetases |
WO2012021247A2 (en) | 2010-07-12 | 2012-02-16 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-trna synthetases |
WO2012027611A2 (en) | 2010-08-25 | 2012-03-01 | Atyr Pharma, Inc. | INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF TYROSYL-tRNA SYNTHETASES |
AU2012284259A1 (en) | 2011-07-15 | 2014-03-06 | Sarepta Therapeutics, Inc. | Methods and compositions for manipulating translation of protein isoforms from alternative initiation start sites |
US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
PT2788487T (pt) | 2011-12-08 | 2018-07-03 | Sarepta Therapeutics Inc | Análogos de oligonucleótido visando lmna humano |
US10006909B2 (en) | 2012-09-28 | 2018-06-26 | Vibrant Holdings, Llc | Methods, systems, and arrays for biomolecular analysis |
KR102275504B1 (ko) | 2013-09-05 | 2021-07-09 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 산성 알파-글루코시다제 내 안티센스-유도된 엑손2 포함 |
US10517898B2 (en) | 2014-11-20 | 2019-12-31 | The Regents Of The University Of California | Compositions and methods related to hematologic recovery |
MA41795A (fr) | 2015-03-18 | 2018-01-23 | Sarepta Therapeutics Inc | Exclusion d'un exon induite par des composés antisens dans la myostatine |
WO2016196670A1 (en) | 2015-06-01 | 2016-12-08 | Sarepta Therapeutics, Inc. | Antisense-induced exon exclusion in type vii collagen |
JP2018525037A (ja) | 2015-08-24 | 2018-09-06 | ハロー−バイオ・アールエヌエーアイ・セラピューティックス、インコーポレイテッド | 遺伝子発現の調節のためのポリヌクレオチドナノ粒子及びその使用 |
WO2017062835A2 (en) | 2015-10-09 | 2017-04-13 | Sarepta Therapeutics, Inc. | Compositions and methods for treating duchenne muscular dystrophy and related disorders |
CN109414511B (zh) | 2016-04-18 | 2023-05-23 | 萨勒普塔医疗公司 | 用于治疗与酸性α-葡糖苷酶基因相关的疾病的反义寡聚物及其使用方法 |
SG11201809468XA (en) | 2016-04-29 | 2018-11-29 | Sarepta Therapeutics Inc | Oligonucleotide analogues targeting human lmna |
TW201811807A (zh) | 2016-06-30 | 2018-04-01 | 美商薩羅塔治療公司 | 用於肌肉萎縮症之外顯子跳躍寡聚物 |
WO2018017814A1 (en) | 2016-07-20 | 2018-01-25 | President And Fellows Of Harvard College | Peptidoglycan glycosyltransferase inhibitors of sed proteins for treating bacterial infections |
US11202818B2 (en) | 2016-09-14 | 2021-12-21 | President And Fellows Of Harvard College | Methods and compositions for modulating erythropoiesis |
WO2018112033A1 (en) | 2016-12-13 | 2018-06-21 | President And Fellows Of Harvard College | Methods and compositions for targeting tumor-infiltrating tregs |
RS63610B1 (sr) | 2016-12-19 | 2022-10-31 | Sarepta Therapeutics Inc | Oligomerni konjugati za preskakanje egzona za mišićnu distrofiju |
US11382981B2 (en) | 2016-12-19 | 2022-07-12 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
AU2017382773A1 (en) | 2016-12-19 | 2019-08-01 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
US11767520B2 (en) | 2017-04-20 | 2023-09-26 | Atyr Pharma, Inc. | Compositions and methods for treating lung inflammation |
US10538808B2 (en) | 2017-05-26 | 2020-01-21 | Vibrant Holdings, Llc | Photoactive compounds and methods for biomolecule detection and sequencing |
EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
US20200248178A1 (en) | 2017-09-28 | 2020-08-06 | Sarepta Therapeutics, Inc. | Combination therapies for treating muscular dystrophy |
JP2020536058A (ja) | 2017-09-28 | 2020-12-10 | サレプタ セラピューティクス, インコーポレイテッド | 筋ジストロフィーを処置するための併用療法 |
EP3687519A1 (en) | 2017-09-28 | 2020-08-05 | Sarepta Therapeutics, Inc. | Combination therapies for treating muscular dystrophy |
JP7394753B2 (ja) | 2017-10-18 | 2023-12-08 | サレプタ セラピューティクス, インコーポレイテッド | アンチセンスオリゴマー化合物 |
US10758629B2 (en) | 2018-05-29 | 2020-09-01 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
EP3806868A4 (en) | 2018-06-13 | 2022-06-22 | Sarepta Therapeutics, Inc. | EXON-SKIPPING OLIGOMERS FOR MUSCULAR DYSTROPHY |
WO2020004980A1 (ko) * | 2018-06-27 | 2020-01-02 | 주식회사 시선바이오머티리얼스 | Pna 올리고머의 제조방법 |
TW202020153A (zh) | 2018-07-27 | 2020-06-01 | 美商薩羅塔治療公司 | 用於肌肉萎縮症之外顯子跳躍寡聚物 |
US11273137B2 (en) | 2018-09-04 | 2022-03-15 | Board Of Trustees Of Michigan State University | Methods and compositions to prevent and treat disorders associated with mutations in the ODC1 gene |
MX2021006737A (es) | 2018-12-13 | 2021-09-23 | Sarepta Therapeutics Inc | Conjugados de oligómeros de salto de exones para distrofia muscular. |
EP4112125A1 (en) | 2019-03-12 | 2023-01-04 | President and Fellows of Harvard College | Methods and compositions for treating cancer |
JP2022528725A (ja) | 2019-04-18 | 2022-06-15 | サレプタ セラピューティクス, インコーポレイテッド | 筋ジストロフィーを治療するための組成物 |
US20220226269A1 (en) | 2019-06-12 | 2022-07-21 | President And Fellows Of Harvard College | Methods and compositions for modulation of an interspecies gut bacterial pathway for levodopa metabolism |
KR102403904B1 (ko) * | 2019-12-24 | 2022-06-02 | 주식회사 시선바이오머티리얼스 | 용액공정상 pna 올리고머의 제조방법 |
WO2021133032A1 (ko) * | 2019-12-24 | 2021-07-01 | 주식회사 시선바이오머티리얼스 | 개질된 감마탄소 골격 화합물 및 이의 제조방법 |
CN115485385A (zh) | 2020-03-04 | 2022-12-16 | 瑞泽恩制药公司 | 用于使肿瘤细胞对免疫疗法敏感的方法和组合物 |
EP4157264A1 (en) | 2020-05-27 | 2023-04-05 | The Regents of the University of California | Compositions and methods for transdifferentiating cells |
WO2022056454A2 (en) | 2020-09-14 | 2022-03-17 | President And Fellows Of Harvard College | Methods and compositions for treating hpv-positive cancers |
US20230340124A1 (en) | 2020-09-16 | 2023-10-26 | President And Fellows Of Harvard College | Methods of treating an individual that has failed an anti-pd-1/anti-pd-l1 therapy |
WO2023055774A1 (en) | 2021-09-30 | 2023-04-06 | Sarepta Therapeutics, Inc. | Antisense oligonucleotides having one or more abasic units |
WO2023070086A1 (en) | 2021-10-22 | 2023-04-27 | Sarepta Therapeutics, Inc. | Morpholino oligomers for treatment of peripheral myelin protein 22 related diseases |
WO2023091704A1 (en) | 2021-11-18 | 2023-05-25 | Circularis Biotechnologies, Inc. | Compositions and methods for production of circular nucleic acid molecules |
WO2023150181A1 (en) | 2022-02-01 | 2023-08-10 | President And Fellows Of Harvard College | Methods and compositions for treating cancer |
WO2024026474A1 (en) | 2022-07-29 | 2024-02-01 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle |
WO2024064237A2 (en) | 2022-09-21 | 2024-03-28 | Sarepta Therapeutics, Inc. | Dmd antisense oligonucleotide-mediated exon skipping efficiency |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2135543A1 (de) * | 1971-07-16 | 1973-01-25 | Boehringer Mannheim Gmbh | Benzthiazolderivate enthaltende arzneimittel |
IT1059127B (it) * | 1976-04-15 | 1982-05-31 | Montedison Spa | Eteri e tioeteri benzilici o feni lici a catena alifatica lineare con terminale alogenato ad attivi ta ormonica giovanile e acaric/da |
US4204870A (en) * | 1978-07-25 | 1980-05-27 | Eastman Kodak Company | Photographic products and processes employing novel nondiffusible heterocyclyazonaphthol dye-releasing compounds |
JPS5827273B2 (ja) * | 1980-06-12 | 1983-06-08 | 三新化学工業株式会社 | ベンゾチアゾ−ル−2−スルホンアミド化合物の製造方法 |
US6713602B1 (en) * | 1991-05-24 | 2004-03-30 | Ole Buchardt | Synthetic procedures for peptide nucleic acids |
DK51092D0 (da) | 1991-05-24 | 1992-04-15 | Ole Buchardt | Oligonucleotid-analoge betegnet pna, monomere synthoner og fremgangsmaade til fremstilling deraf samt anvendelser deraf |
US6228982B1 (en) * | 1992-05-22 | 2001-05-08 | Benget Norden | Double-stranded peptide nucleic acids |
JPH05140115A (ja) * | 1991-11-14 | 1993-06-08 | Sanshin Chem Ind Co Ltd | スルホンアミド系化合物及びゴム組成物 |
US6277603B1 (en) * | 1991-12-24 | 2001-08-21 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
US5700922A (en) * | 1991-12-24 | 1997-12-23 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
JPH06298749A (ja) * | 1993-02-19 | 1994-10-25 | Asahi Chem Ind Co Ltd | ベンゾチアゾールスルホンアミド誘導体 |
US6350853B1 (en) * | 1993-04-26 | 2002-02-26 | Peter E. Nielsen | Conjugated peptide nucleic acids having enhanced cellular uptake |
RU2118322C1 (ru) * | 1993-07-05 | 1998-08-27 | Дюфар Интернэшнл Рисерч Б.В. | 2,3-дигидро-1,4-бензодиокси-5-ил-пиперазиновые производные или их соли |
US5435939A (en) * | 1993-07-07 | 1995-07-25 | Isp Investments Inc. | Stable emulsifiable gel matrix and aqueous macroemulsion prepared therefrom |
US6133444A (en) * | 1993-12-22 | 2000-10-17 | Perseptive Biosystems, Inc. | Synthons for the synthesis and deprotection of peptide nucleic acids under mild conditions |
US5539083A (en) * | 1994-02-23 | 1996-07-23 | Isis Pharmaceuticals, Inc. | Peptide nucleic acid combinatorial libraries and improved methods of synthesis |
DE69632324T2 (de) * | 1995-06-07 | 2005-06-16 | PerSeptive Biosystems, Inc., Framingham | Pna-dna-chimäre und pna-synthone zu deren herstellung |
DE19532553A1 (de) * | 1995-09-04 | 1997-03-06 | Hoechst Ag | Verfahren zur Herstellung substituierter N-Ethyl-Glycinderivate |
JPH11199573A (ja) * | 1998-01-07 | 1999-07-27 | Yamanouchi Pharmaceut Co Ltd | 5ht3受容体作動薬及び新規ベンゾチアゾール誘導体 |
WO1999037304A1 (en) * | 1998-01-27 | 1999-07-29 | Aventis Pharmaceuticals Products Inc. | SUBSTITUTED OXOAZAHETEROCYCLYL FACTOR Xa INHIBITORS |
DE69933770D1 (de) | 1998-07-09 | 2006-12-07 | Biocept Inc | Verfahren zur verwendung einer universellen bibliothek von peptid-nukleinsäuren zur optimierung der dns-hybridisierung |
SE9802538D0 (sv) | 1998-07-13 | 1998-07-13 | Astra Ab | New pharmaceutically active compounds |
KR100464261B1 (ko) * | 2002-01-24 | 2005-01-03 | 주식회사 파나진 | Pna 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
US7211668B2 (en) * | 2003-07-28 | 2007-05-01 | Panagene, Inc. | PNA monomer and precursor |
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