RU2013151977A - КОНЪЮГАТ миРНК И СПОСОБ ЕГО ПОЛУЧЕНИЯ - Google Patents
КОНЪЮГАТ миРНК И СПОСОБ ЕГО ПОЛУЧЕНИЯ Download PDFInfo
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- RU2013151977A RU2013151977A RU2013151977/10A RU2013151977A RU2013151977A RU 2013151977 A RU2013151977 A RU 2013151977A RU 2013151977/10 A RU2013151977/10 A RU 2013151977/10A RU 2013151977 A RU2013151977 A RU 2013151977A RU 2013151977 A RU2013151977 A RU 2013151977A
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- 238000000034 method Methods 0.000 title claims 2
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 108020004459 Small interfering RNA Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 19
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract 12
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract 12
- 239000007787 solid Substances 0.000 claims abstract 12
- -1 polyethylene Polymers 0.000 claims abstract 10
- 239000004698 Polyethylene Substances 0.000 claims abstract 6
- 229920000573 polyethylene Polymers 0.000 claims abstract 6
- 239000011148 porous material Substances 0.000 claims abstract 6
- 239000000758 substrate Substances 0.000 claims abstract 5
- 239000011521 glass Substances 0.000 claims abstract 4
- 125000003342 alkenyl group Chemical group 0.000 claims abstract 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract 3
- 125000000304 alkynyl group Chemical group 0.000 claims abstract 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract 3
- 125000003118 aryl group Chemical group 0.000 claims abstract 3
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract 3
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 3
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims abstract 2
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 claims abstract 2
- JBWYRBLDOOOJEU-UHFFFAOYSA-N 1-[chloro-(4-methoxyphenyl)-phenylmethyl]-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1C(Cl)(C=1C=CC(OC)=CC=1)C1=CC=CC=C1 JBWYRBLDOOOJEU-UHFFFAOYSA-N 0.000 claims abstract 2
- 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 abstract 2
- 150000003973 alkyl amines Chemical class 0.000 claims abstract 2
- 230000015572 biosynthetic process Effects 0.000 claims abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- 229940126214 compound 3 Drugs 0.000 claims 1
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Abstract
1. Связанная с полиэтиленгликолем твердая подложка, имеющая следующую структуру:,где R представляет собой алкил, алкенил, алкинил, арил, арилалкил, гетероалкил или гетероарил; m представляет собой целое число от 2 до 18; n представляет собой целое число от 5 до 120; и X представляет собой атом водорода, -монометокситритила, 4,4'-диметокситритил или 4,4',4"-триметокситритила.2. Связанная с полиэтиленгликолем твердая подложка по п. 1, где твердая подложка представляет собой стекло с контролируемым размером пор (СКП).3. Связанная с полиэтиленгликолем твердая подложка по п. 2, в которой СКП имеет диаметр от 40 до 180 мкм и размер пор от 500 до 3000 Å.4. Связанная с полиэтиленгликолем твердая подложка по п. 1, в которой связанная с полиэтиленгликолем твердая подложка представляет собой соединение 3'-ПЭГ(полиэтиленгликоль)-СКП, имеющее следующую структурную формулу IV: [Структурная формула IV]5. Способ получения соединения 3'-ПЭГ-СКП, имеющего следующую структурную формулу IV, который предусматривает:1) реакцию СКП с 3-аминопропилтриэтоксисиланом, с образованием соединения длинноцепочечного алкиламина и стекла с контролируемым размером пор (ДЦАА-СКП);2) реакцию полиэтиленгликоля с 4,4'-диметокситритилхлоридом, в которой образуется 2-[бис-(4-диметокситритил)полиэтиленгликоль)];3) реакцию соединения, полученного на стадии (2), с соединением, имеющим следующую формулу 1, с образованием соединения, имеющего следующую структурную формулу I;4) реакцию полученного соединения, имеющего следующую структурную формулу I, с 4-нитрофенилхлорформиатом, с образованием соединения, имеющего следующую структурную формулу II;5) реакцию соединения, имеющего следующую струк
Claims (5)
1. Связанная с полиэтиленгликолем твердая подложка, имеющая следующую структуру:
где R представляет собой алкил, алкенил, алкинил, арил, арилалкил, гетероалкил или гетероарил; m представляет собой целое число от 2 до 18; n представляет собой целое число от 5 до 120; и X представляет собой атом водорода, -монометокситритила, 4,4'-диметокситритил или 4,4',4"-триметокситритила.
2. Связанная с полиэтиленгликолем твердая подложка по п. 1, где твердая подложка представляет собой стекло с контролируемым размером пор (СКП).
3. Связанная с полиэтиленгликолем твердая подложка по п. 2, в которой СКП имеет диаметр от 40 до 180 мкм и размер пор от 500 до 3000 Å.
5. Способ получения соединения 3'-ПЭГ-СКП, имеющего следующую структурную формулу IV, который предусматривает:
1) реакцию СКП с 3-аминопропилтриэтоксисиланом, с образованием соединения длинноцепочечного алкиламина и стекла с контролируемым размером пор (ДЦАА-СКП);
2) реакцию полиэтиленгликоля с 4,4'-диметокситритилхлоридом, в которой образуется 2-[бис-(4-диметокситритил)полиэтиленгликоль)];
3) реакцию соединения, полученного на стадии (2), с соединением, имеющим следующую формулу 1, с образованием соединения, имеющего следующую структурную формулу I;
4) реакцию полученного соединения, имеющего следующую структурную формулу I, с 4-нитрофенилхлорформиатом, с образованием соединения, имеющего следующую структурную формулу II;
5) реакцию соединения, имеющего следующую структурную формулу I и полученного на стадии (3), с N-сукцинимидилтрифторуксусной кислотой, с образованием соединения, имеющего следующую структурную формулу III; и
6) реакцию соединения ДЦАА-СКП, полученного на стадии (1), с соединениями, имеющими следующие структурные формулы I, II или III, соответственно, и полученными на стадиях (3)-(5), соответственно.
[Формула 1]
[Структурная формула I]
[Структурная формула II]
[Структурная формула III]
[Структурная формула IV]
(где R представляет собой алкил, алкенил, алкинил, арил, арилалкил, гетероалкил или гетероарил; и n представляет собой целое число, составляющее не менее чем 5 и не более чем 120).
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