DE69930647T2 - Struktur-analoga von amin-basen und nucleosiden - Google Patents
Struktur-analoga von amin-basen und nucleosiden Download PDFInfo
- Publication number
- DE69930647T2 DE69930647T2 DE69930647T DE69930647T DE69930647T2 DE 69930647 T2 DE69930647 T2 DE 69930647T2 DE 69930647 T DE69930647 T DE 69930647T DE 69930647 T DE69930647 T DE 69930647T DE 69930647 T2 DE69930647 T2 DE 69930647T2
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- Germany
- Prior art keywords
- group
- hydrogen
- compound
- hydroxyl
- protecting group
- 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
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- 239000002777 nucleoside Substances 0.000 title claims description 60
- -1 Iodoacetamidyl Chemical group 0.000 claims description 135
- 229910052739 hydrogen Inorganic materials 0.000 claims description 94
- 239000001257 hydrogen Substances 0.000 claims description 93
- 125000003118 aryl group Chemical group 0.000 claims description 52
- 125000006239 protecting group Chemical group 0.000 claims description 52
- 150000002431 hydrogen Chemical class 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 150000001875 compounds Chemical class 0.000 claims description 36
- 150000001408 amides Chemical class 0.000 claims description 32
- 239000000126 substance Substances 0.000 claims description 32
- 150000001412 amines Chemical class 0.000 claims description 31
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 26
- 125000003277 amino group Chemical group 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 18
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
- 230000002194 synthesizing effect Effects 0.000 claims description 13
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 12
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 238000010647 peptide synthesis reaction Methods 0.000 claims description 11
- 125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- 239000012038 nucleophile Substances 0.000 claims description 10
- 150000002730 mercury Chemical class 0.000 claims description 9
- 125000006245 phosphate protecting group Chemical group 0.000 claims description 9
- 239000001226 triphosphate Substances 0.000 claims description 9
- 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 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 230000005494 condensation Effects 0.000 claims description 7
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 7
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 claims description 7
- 125000002339 acetoacetyl group Chemical group O=C([*])C([H])([H])C(=O)C([H])([H])[H] 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 claims description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 6
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 6
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 238000009833 condensation Methods 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 claims description 3
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 claims description 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims description 3
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 claims description 3
- 125000005252 haloacyl group Chemical group 0.000 claims description 3
- 150000002540 isothiocyanates Chemical class 0.000 claims description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 3
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000006000 trichloroethyl group Chemical group 0.000 claims description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 2
- CRAJLXHBNCCDPK-UHFFFAOYSA-N 2,2,2-trichloroethyl hydrogen carbonate Chemical group OC(=O)OCC(Cl)(Cl)Cl CRAJLXHBNCCDPK-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 25
- 108091034117 Oligonucleotide Proteins 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000000523 sample Substances 0.000 description 19
- 125000003835 nucleoside group Chemical group 0.000 description 18
- 108020004414 DNA Proteins 0.000 description 17
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Saccharide Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/130,373 US6335432B1 (en) | 1998-08-07 | 1998-08-07 | Structural analogs of amine bases and nucleosides |
| US130373 | 1998-08-07 | ||
| PCT/US1999/017587 WO2000008041A1 (en) | 1998-08-07 | 1999-08-04 | Structural analogs of amine bases and nucleosides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69930647D1 DE69930647D1 (de) | 2006-05-18 |
| DE69930647T2 true DE69930647T2 (de) | 2007-01-11 |
Family
ID=22444397
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69930647T Expired - Lifetime DE69930647T2 (de) | 1998-08-07 | 1999-08-04 | Struktur-analoga von amin-basen und nucleosiden |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6335432B1 (cg-RX-API-DMAC10.html) |
| EP (1) | EP1102782B1 (cg-RX-API-DMAC10.html) |
| JP (1) | JP4623828B2 (cg-RX-API-DMAC10.html) |
| CA (1) | CA2339967C (cg-RX-API-DMAC10.html) |
| DE (1) | DE69930647T2 (cg-RX-API-DMAC10.html) |
| WO (1) | WO2000008041A1 (cg-RX-API-DMAC10.html) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050119470A1 (en) * | 1996-06-06 | 2005-06-02 | Muthiah Manoharan | Conjugated oligomeric compounds and their use in gene modulation |
| US20040203024A1 (en) * | 1996-06-06 | 2004-10-14 | Baker Brenda F. | Modified oligonucleotides for use in RNA interference |
| US7812149B2 (en) * | 1996-06-06 | 2010-10-12 | Isis Pharmaceuticals, Inc. | 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations |
| US20050053976A1 (en) * | 1996-06-06 | 2005-03-10 | Baker Brenda F. | Chimeric oligomeric compounds and their use in gene modulation |
| US20040171031A1 (en) * | 1996-06-06 | 2004-09-02 | Baker Brenda F. | Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| US20080119427A1 (en) * | 1996-06-06 | 2008-05-22 | Isis Pharmaceuticals, Inc. | Double Strand Compositions Comprising Differentially Modified Strands for Use in Gene Modulation |
| US20040147022A1 (en) * | 1996-06-06 | 2004-07-29 | Baker Brenda F. | 2'-methoxy substituted oligomeric compounds and compositions for use in gene modulations |
| US9096636B2 (en) | 1996-06-06 | 2015-08-04 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds and their use in gene modulation |
| US5898031A (en) * | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| DE19935302A1 (de) | 1999-07-28 | 2001-02-08 | Aventis Pharma Gmbh | Konjugate und Verfahren zu deren Herstellung sowie deren Verwendung zum Transport von Molekülen über biologische Membranen |
| US8604183B2 (en) * | 2002-11-05 | 2013-12-10 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2′-modified nucleosides for use in gene modulation |
| WO2005044976A2 (en) * | 2003-06-20 | 2005-05-19 | Isis Pharmaceuticals, Inc. | Oligomeric compounds for use in gene modulation |
| US8569474B2 (en) * | 2004-03-09 | 2013-10-29 | Isis Pharmaceuticals, Inc. | Double stranded constructs comprising one or more short strands hybridized to a longer strand |
| US8394947B2 (en) * | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
| US7884086B2 (en) * | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
| US20100280098A1 (en) * | 2007-10-05 | 2010-11-04 | Juliano Rudolph L | Receptor targeted oligonucleotides |
| US9778188B2 (en) | 2009-03-11 | 2017-10-03 | Industrial Technology Research Institute | Apparatus and method for detection and discrimination molecular object |
| US9482615B2 (en) | 2010-03-15 | 2016-11-01 | Industrial Technology Research Institute | Single-molecule detection system and methods |
| US9670243B2 (en) | 2010-06-02 | 2017-06-06 | Industrial Technology Research Institute | Compositions and methods for sequencing nucleic acids |
| US8865078B2 (en) | 2010-06-11 | 2014-10-21 | Industrial Technology Research Institute | Apparatus for single-molecule detection |
| WO2012044992A2 (en) | 2010-09-30 | 2012-04-05 | Agency For Science, Technology And Research (A*Star) | Methods and reagents for detection and treatment of esophageal metaplasia |
| CA2889044A1 (en) | 2012-11-15 | 2014-05-22 | Roche Innovation Center Copenhagen A/S | Anti apob antisense conjugate compounds |
| CA2893801A1 (en) | 2013-01-30 | 2014-08-07 | F. Hoffmann-La Roche Ag | Lna oligonucleotide carbohydrate conjugates |
| WO2014118272A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Antimir-122 oligonucleotide carbohydrate conjugates |
| MX367083B (es) | 2013-06-27 | 2019-08-05 | Roche Innovation Ct Copenhagen As | Oligomeros antisentido y conjugados con diana en la proteina-convertasa subtilisina/kexina tipo 9(pcsk9). |
| JP6226318B2 (ja) * | 2013-09-02 | 2017-11-08 | 株式会社 資生堂 | 光学分割用化合物、光学分割用試薬、光学分割する方法及び光学異性体 |
| GB201408623D0 (en) | 2014-05-15 | 2014-07-02 | Santaris Pharma As | Oligomers and oligomer conjugates |
| CA3013683C (en) | 2016-03-14 | 2021-07-13 | F. Hoffmann-La Roche Ag | Oligonucleotides for reduction of pd-l1 expression |
| CR20230308A (es) | 2020-12-11 | 2023-09-08 | Civi Biopharma Inc | Entrega oral de conjugados antisentido que tienen por blanco a pcsk9 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1219824A (en) * | 1981-04-17 | 1987-03-31 | David C. Ward | Modified nucleotides and methods of preparing and using same |
| EP0235301B1 (en) * | 1985-09-09 | 1992-07-22 | Teijin Limited | Pyridopyrimidine nucleotide derivatives |
| JPH07165786A (ja) * | 1993-12-10 | 1995-06-27 | Hiroaki Sawai | ５位置換ウリジン類、その製造方法及びその用途 |
| CA2274587A1 (en) * | 1996-12-10 | 1998-06-18 | Genetrace Systems Inc. | Releasable nonvolatile mass-label molecules |
-
1998
- 1998-08-07 US US09/130,373 patent/US6335432B1/en not_active Expired - Lifetime
-
1999
- 1999-08-04 DE DE69930647T patent/DE69930647T2/de not_active Expired - Lifetime
- 1999-08-04 CA CA2339967A patent/CA2339967C/en not_active Expired - Lifetime
- 1999-08-04 EP EP99940867A patent/EP1102782B1/en not_active Expired - Lifetime
- 1999-08-04 JP JP2000563674A patent/JP4623828B2/ja not_active Expired - Lifetime
- 1999-08-04 WO PCT/US1999/017587 patent/WO2000008041A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000008041A9 (en) | 2001-02-01 |
| EP1102782A1 (en) | 2001-05-30 |
| CA2339967A1 (en) | 2000-02-17 |
| DE69930647D1 (de) | 2006-05-18 |
| US6335432B1 (en) | 2002-01-01 |
| WO2000008041A1 (en) | 2000-02-17 |
| EP1102782A4 (en) | 2002-01-30 |
| JP4623828B2 (ja) | 2011-02-02 |
| CA2339967C (en) | 2011-06-07 |
| JP2002522446A (ja) | 2002-07-23 |
| EP1102782B1 (en) | 2006-03-29 |
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| 8364 | No opposition during term of opposition |