RU2494089C2 - Соединения, представляющие собой стиролильные производные, для лечения офтальмических заболеваний и расстройств - Google Patents

Соединения, представляющие собой стиролильные производные, для лечения офтальмических заболеваний и расстройств Download PDF

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RU2494089C2
RU2494089C2 RU2009136911/04A RU2009136911A RU2494089C2 RU 2494089 C2 RU2494089 C2 RU 2494089C2 RU 2009136911/04 A RU2009136911/04 A RU 2009136911/04A RU 2009136911 A RU2009136911 A RU 2009136911A RU 2494089 C2 RU2494089 C2 RU 2494089C2
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phenyl
propan
alkyl
amine
vinyl
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RU2009136911/04A
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RU2009136911A (ru
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Айан Лесли СКОТТ
Владимир Александрович Кукса
Анна ГАЛЛ
Марк У. Орм
Дженнифер Гейдж
Томас Л. мл. ЛИТТЛ
Кин ДЖИАНГ
Лана Мишель РОССИТЕР
Кевин Ф. мл. МАКГИ
Рьо КУБОТА
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Акьюсела Инк.
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
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Abstract

Изобретение относится к новым стирольным производным, имеющим структурную формулу (А) в виде геометрических изомеров или таутомеров, и их фармацевтически приемлемым солям. Соединения могут быть использованы для лечения офтальмического заболевания или расстройства у субъекта, которые могут представлять собой возрастную дегенерацию желтого пятна или макулярную дистрофию Штаргардта. В структурной формуле (А)
Figure 00000389
,
R1 представляет собой водород; R2 представляет собой водород или C1-C6алкил; R3, R4, R5 и R6 являются одинаковыми или разными и независимо представляют собой водород, галоген, C1-C6алкил или -OR12; R7 представляет собой водород или C1-C6алкил; R8 представляет собой водород; R9 представляет собой водород, C1-6алкил или -C(=O)R13; R10 представляет собой водород или C1-C6алкил; Z представляет собой W-Y, где W представляет собой -C(R14)(R15)-; Y представляет собой -C(R16)(R17)-; каждый R12 независимо представляет собой водород или C1-C6алкил; каждый R13 независимо представляет собой C1-C6алкил; R14 и R15 являются одинаковыми или разными и независимо выбраны из водорода, фторо, метила, этила, трифторметила, -OН, -OСН3 или -NH2; или R14 и R15 вместе образуют оксо; R16 и R17 являются одинаковыми или разными и независимо представляют собой водород, галоген, C1-C6алкил или -OR12. Значения остальных радикалов указаны в формуле изобретения. 3 н. и 14 з.п. ф-лы, 14 табл., 143 пр.

Description

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Claims (17)

1. Соединение, имеющее структуру формулы (А):
Figure 00000386
,
в виде отдельного E- или Z-геометрического изомера или смеси E- и Z-геометрических изомеров, в виде таутомера или смеси таутомеров, в виде стереоизомера или в виде фармацевтически приемлемой соли, где
R1 представляет собой водород;
R2 представляет собой водород или C1-C6алкил;
R3, R4, R5 и R6 являются одинаковыми или разными и независимо представляют собой водород, галоген, C1-C6алкил или -OR12;
R7 представляет собой водород или C1-C6алкил;
R8 представляет собой водород;
R9 представляет собой водород, C1-C6алкил, или -C(=O)R13;
R10 представляет собой водород или C1-C6алкил;
Z представляет собой W-Y, где
W представляет собой -C(R14)(R15)-;
Y представляет собой -C(R16)(R17)-;
каждый R12 независимо представляет собой водород или C1-C6алкил;
каждый R13 независимо представляет собой C1-C6алкил;
R14 и R15 являются одинаковыми или разными и независимо выбраны из водорода, фторо, метила, этила, трифторметила, -OH, -OCH3 или -NH2; или R14 и R15 вместе образуют оксо;
R16 и R17 являются одинаковыми или разными и независимо представляют собой водород, галоген, C1-C6алкил или -OR12; или R16 и R17 вместе образуют оксо; или
возможно, R14 и R16 вместе образуют прямую связь, обеспечивая образование двойной связи, соединяющей W и Y; или возможно, R14 и R16 вместе образуют прямую связь, и R15 и R17 вместе образуют прямую связь, обеспечивая образование тройной связи, соединяющей W и Y; и
R11 выбран из:
а) C1-C6алкила;
б) фенила, замещенного C1-C6алкилом, -OR12, -O(CH2)mOCH3, где m равен 1-6, C2-C6алкенилом, C2-C6алкинилом, галогеном, фторC1-C6алкилом, фенилом, -SCH3 или C6-C10арилC1-C6алкилом;
в) нафтенила, возможно замещенного C1-C6алкилом, галогеном или -OR12; или
г) карбоциклила, выбранного из насыщенного или частично насыщенного C5-C7циклоалкила, возможно замещенного C1-C6алкилом, -OR12, C2-C6алкенилом, C2-C6алкинилом, галогено, фторC1-C6алкилом или C6-C10арилC1-C6алкилом;
при условии, что R11 не представляет собой 3,4,5-три-метоксифенил.
2. Соединение по п.1, где R11 представляет собой:
фенил, замещенный C1-C6алкилом, -OR12, -O(CH2)mOCH3, где m равен 1-6, C2-C6алкенилом, C2-C6алкинилом, галогеном, фторC1-C6алкилом, фенилом, -SCH3 или C6-C10арилC1-C6алкилом;
нафтенил, возможно замещенный C1-C6алкилом, галогеном или -OR12; или
карбоциклил, выбранный из насыщенного или частично насыщенного C5-7циклоалкила, возможно замещенного C1-C6алкилом, -OR12, C2-C6алкенилом, C2-C6алкинилом, галогено, фторC1-C6алкилом или C6-C10арилC1-C6алкилом.
3. Соединение по п.2, имеющее структуру формулы (Д):
Figure 00000387
,
в виде отдельного E- или Z-геометрического изомера или смеси E- и Z-геометрических изомеров, в виде таутомера или смеси таутомеров, в виде стереоизомера или в виде фармацевтически приемлемой соли, где
R1 представляет собой водород;
R2 представляет собой водород или C1-C6алкил;
R3, R4, R5 и R6 являются одинаковыми или разными и независимо представляют собой водород, галоген, -OR12 или C1-C6алкил;
R7 представляет собой водород или C1-C6алкил;
R8 представляет собой водород;
каждый R12 независимо представляет собой водород или C1-C6алкил;
R14 и R15 являются одинаковыми или разными и независимо выбраны из водорода, фторо, метила, этила, трифторметила, -OH, -OCH3 или -NH2; или R14 и R15 вместе образуют оксо;
R16 и R17 являются одинаковыми или разными и независимо представляют собой водород, галоген, C1-C6алкил или -OR12; или R16 и R17 вместе образуют оксо;
t равен 0, 1, 2 или 3; и
каждый R20 является одинаковым или разным и независимо представляет собой C1-C6алкил, -OR12, C2-C6алкенил, C2-C6алкинил, галогено, фторC1-C6алкил, фенил, -SCH3 или C6-C10арилC1-C6алкил.
4. Соединение по п.2, где R11 представляет собой нафтенил, замещенный -OR12, где R12 представляет собой водород или C1-C6алкил.
5. Соединение по п.2, где R11 представляет собой карбоциклил, выбранный из насыщенного или частично насыщенного C5-C7циклоалкила.
6. Соединение по п.5, где R11 представляет собой 5-, 6- или 7-членный циклоалкенил.
7. Соединение по п.6, имеющее структуру формулы (Ж):
Figure 00000388

в виде отдельного E- или Z-геометрического изомера или смеси E- и Z-геометрических изомеров, в виде таутомера или смеси таутомеров, в виде стереоизомера или в виде фармацевтически приемлемой соли, где
R1 представляет собой водород;
R2 представляет собой водород или C1-C6алкил;
R3, R4, R5 и R6 являются одинаковыми или разными и независимо представляют собой водород, галоген, -OR12 или C1-C6алкил;
R7 представляет собой водород или C1-C6алкил;
R8 представляет собой водород;
R9 представляет собой водород, C1-C6алкил или -C(=O)R13;
R10 представляет собой водород или C1-C6алкил;
каждый R12 независимо представляет собой водород или C1-C6алкил;
каждый R13 независимо представляет собой C1-C6алкил;
R14 и R15 являются одинаковыми или разными и независимо выбраны из водорода, фторо, метила, этила, трифторметила, -OH, -OCH3 или -NH2; или R14 и R15 вместе образуют оксо;
R16 и R17 являются одинаковыми или разными и независимо представляют собой водород, галоген, C1-C6алкил или -OR12; или R16 и R17 вместе образуют оксо;
возможно, R14 и R16 вместе образуют прямую связь, обеспечивая образование двойной связи, соединяющей W и Y; или R14 и R16 вместе образуют прямую связь, и R15 и R17 вместе образуют прямую связь, обеспечивая образование тройной связи, соединяющей W и Y;
p равен 0, 1, 2 или 3; и
каждый R21 является одинаковым или разным по отношению к каждому и независимо представляет собой C1-C6алкил, -OR12, C2-C6алкенил, C2-C6алкинил, галогено, фторC1-C6алкил или C6-C10арилC1-C6алкил.
8. Соединение по п.7, где каждый из R9 и R10 представляет собой водород.
9. Соединение по п.8, где
каждый из R1 и R2 представляет собой водород;
p равен 0, 1, 2 или 3;
каждый R21 независимо представляет собой C1-C6алкил, галогено или фторC1-C6алкил; и
каждый из R3, R4, R5 и R6 независимо представляет собой водород, C1-C6алкил, галогено или -OR12.
10. Соединение по п.7, где R9 представляет собой C1-C6алкил, и R10 представляет собой водород.
11. Соединение по п.10, где
каждый из R1 и R2 представляет собой водород;
p равен 0, 1, 2 или 3;
каждый R21 независимо представляет собой C1-C6алкил, галогено или фторC1-C6алкил; и
каждый из R3, R4, R5 и R6 независимо представляет собой водород, C1-C6алкил, галогено или -OR12.
12. Соединение по п.7, где
R7 представляет собой водород или C1-C6алкил;
R8 представляет собой водород;
каждый из R16 и R17 независимо представляет собой водород, галоген, C1-C6алкил или -OR12, где R12 независимо представляет собой водород или C1-C6алкил; и R14 и R15 вместе образуют оксо.
13. Соединение по п.2, где R11 представляет собой C1-C6алкил и каждый из R9 и R10 представляет собой водород.
14. Соединение, выбранное из:
(E)-3-(3-(2,6-диметилстирил)фенил)пропан-1-амина;
(Z)-3-(3-(2,6-диметилстирил)фенил)пропан-1-амина;
(E)-3-(3-(2-метилстирил)фенил)пропан-1-амина;
(Z)-3-(3-(2-метилстирил)фенил)пропан-1-амина;
(E)-3-(3-(2,6-диметилстирил)-2-метилфенил)пропан-1-амина;
(Z)-3-(3-(2,6-диметилстирил)-2-метилфенил)пропан-1-амина;
(E/Z)-3-(3-(2-этил-6-метилстирил)фенил)пропан-1-амина;
(E/Z)-3-(3-(2,5-диметилстирил)фенил)пропан-1-амина;
(E/Z)-3-(3-(2,4-диметилстирил)фенил)пропан-1-амина;
(E)-3-(3-(2,4,6-триметилстирил)фенил)пропан-1-амина;
(E/Z)-3-(3-(2-этилстирил)фенил)пропан-1-амина;
(E/Z)-3-(3-(2-этинилстирил)фенил)пропан-1-амина;
(E/Z)-3-(3-(3,4-диметилстирил)фенил)пропан-1-амина;
(E/Z)-3-(3-(2-изопропилстирил)фенил)пропан-1-амина;
(E/Z)-4-(3-(3,5-диметилстирил)фенил)пропан-1-амина;
(E/Z)-4-(3-(2-метоксистирил)фенил)пропан-1-амина;
(E)-3-(3-(2,6-дихлорстирил)фенил)пропан-1-амина;
(E/Z)-3-(3-(2,3-диметилстирил)фенил)пропан-1-амина;
(E)-3-(3-(2,6-диметилстирил)-4-фторфенил)пропан-1-амина;
(E/Z)-3-(3-(2-(трифторметил)стирил)фенил)пропан-1-амина;
(E)-3-(3-(2,6-диметоксистирил)фенил)пропан-1-амина;
(E)-3-(3-(2,6-бис(трифторметил)стирил)фенил)пропан-1-амина;
(E)-3-амино-1-(3-(2,6-дихлорстирил)фенил)пропан-1-ола;
(E)-3-амино-1-(3-(2-хлор-6-метилстирил)фенил)пропан-1-ола;
(E)-2-(3-(3-аминопропил)стирил)фенола;
(E)-3-(5-(2,6-дихлорстирил)-2-метоксифенил)пропан-1-амина;
(R,E)-1-амино-3-(3-(2,6-дихлорстирил)фенил)пропан-2-ола;
(S,E)-1-амино-3-(3-(2,6-дихлорстирил)фенил)пропан-2-ола;
(E/Z)-(3-(3-(2,6-диэтоксистирил)фенил)пропан-1-амина;
(E)-3-(3-(2-этоксистирил)фенил)пропан-1-амина;
(E/Z)-3-(3-(2-изопропоксистирил)фенил)пропан-1-амина;
(E)-3-амино-1-(3-(2,6-дихлорстирил)фенил)пропан-1-она;
(E)-1-амино-3-(3-(2,6-дихлорстирил)фенил)пропан-2-она;
(R,E)-3-амино-1-(3-(2,6-дихлорстирил)фенил)пропан-1-ола;
(S,E)-3-амино-1-(3-(2,6-дихлорстирил)фенил)пропан-1-ола;
(S,E)-3-(3-(2,6-дихлорстирил)фенил)-2-фторпропан-1-амина;
(E)-3-(3-(2,6-дихлорстирил)фенил)-2,2-дифторпропан-1-амина;
(Z)-3-(3-(2-(2-метоксиэтокси)стирил)фенил)-пропан-1-амина;
(E)-3-(3-(3-метоксистирил)фенил)пропан-1-амина;
(Z)-3-(3-(4-хлорстирил)фенил)пропан-1-амина;
(E)-3-(3-(2-(бифенил-2-ил)винил)фенил)пропан-1-амина;
(E)-3-(3-(3-хлорстирил)фенил)пропан-1-амина;
(E)-3-(3-(2-бутоксистирил)фенил)пропан-1-амина;
(E)-3-(3-(4-метоксистирил)фенил)пропан-1-амина;
(Z)-3-(3-(2-пропоксистирил)фенил)пропан-1-амина;
(E)-3-(5-(2-хлор-6-(метилтио)стирил)-2-метоксифенил)пропан-1-амина;
(E)-3-(3-(2-(1-метоксинафталин-2-ил)винил)фенил)пропан-1-амина;
(Z)-3-(3-(2-(нафталин-1-ил)винил)фенил)пропан-1-амина;
(Z)-3-(3-(2-(3-метоксинафталин-2-ил)винил)фенил)пропан-1-амина;
(E/Z)-3-(3-(2-(2-метоксинафталин-1-ил)винил)фенил)пропан-1-амина;
(E)-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-амина;
(E)-3-амино-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-ола;
(S,E)-3-амино-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-ола;
(R,E)-3-амино-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-ола;
(E)-2-метил-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-амина;
(E)-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)бутан-1-амина;
(E)-3-(2-метил-5-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-амина;
(E/Z)-4-амино-2-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)бутан-2-ола;
(E)-3-фтор-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-амина;
(E)-4-амино-1,1,1-трифтор-2-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)бутан-2-ола;
(E)-3-амино-2,2-диметил-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-ола;
(E)-3-амино-2-метил-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-ола;
(E)-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1,3-диамина;
(E)-4,4,4-трифтор-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)бутан-1-амина;
(E)-3-метокси-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-амина;
(E)-4-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)бутан-2-амина;
(E)-1-амино-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-2-ола;
(E)-2-(3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропиламино)этанола;
(E)-3-метокси-N-метил-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1 -амина;
(E)-3-амино-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-она;
(E)-3-амино-2,2-диметил-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-она;
(E)-3-амино-2-метил-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-она;
(E)-3-амино-2-фтор-1-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)пропан-1-она;
(E)-2-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенокси)этанамина;
(E)-2-амино-N-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)ацетамида;
(E)-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)проп-2-ин-1-амина;
(E)-2-фтор-3-(3-((E)-2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)проп-2-ен-1-амина;
(E)-3-(3-(2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)проп-2-ин-1-амина;
(E)-2-фтор-3-(3-((E)-2-(2,6,6-триметилциклогекс-1-енил)винил)фенил)проп-2-ен-1-амина;
(E)-3-(3-(пент-1-енил)фенил)пропан-1-амина;
(E)-3-(3-(гепт-1-енил)фенил)пропан-1-амина;
(E)-3-(3-(нон-4-ен-5-ил)фенил)пропан-1-амина;
(E)-4-(3-(3-аминопропил)фенил)-2-метилбут-3-ен-2-ола;
(Е)-4-(3-(3-аминопропил)стирил)гептан-4-ола;
(E)-1-(3-(3-аминопропил)фенил)гекс-1-ен-3-ола;
(E)-1-(3-(3-аминопропил)фенил)-3-этилпент-1-ен-3-ола;
(E)-3-(3-(3-аминопропил)фенил)проп-2-ен-1-ола;
(E)-3-(3-(3-метоксипроп-1-енил)фенил)пропан-1-амина;
(E)-1-(3-(3-аминопропил)фенил)-3-метилгекс-1-ен-3-ола и
(E)-1-(3-(3-аминопропил)фенил)-3-этилгекс-1-ен-3-ола.
15. Фармацевтическая композиция для лечения офтальмического заболевания или расстройства, содержащая фармацевтически приемлемый носитель и соединение по любому из пп.1-14 в эффективном количестве.
16. Фармацевтическая композиция по п.15 для лечения офтальмического заболевания или расстройства у субъекта.
17. Фармацевтическая композиция по п.16, где офтальмическое заболевание или расстройство представляет собой возрастную дегенерацию желтого пятна или макулярную дистрофию Штаргардта.
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Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2008242626B2 (en) 2007-04-20 2012-04-12 Acucela Inc. Styrenyl derivative compounds for treating ophthalmic diseases and disorders
MX2010004718A (es) 2007-11-01 2010-07-28 Acucela Inc Compuestos derivados de amina para tratar enfermedades y trastornos oftalmicos.
AU2009308483C1 (en) 2008-10-22 2014-01-23 Acucela, Inc. Compounds for treating ophthalmic diseases and disorders
WO2012150208A1 (de) 2011-05-04 2012-11-08 Bayer Cropscience Ag Verwendung von substituierten benzylalkoholestern der cyclopropancarbonsäure zur bekämpfung von insektizid-resistenten insekten
BR112014012997A2 (pt) * 2011-11-30 2017-06-13 Bikam Pharmaceuticals Inc ligantes que se ligam à opsina, composições e métodos de uso
EP2804605A4 (en) 2012-01-20 2015-07-08 Acucela Inc SUBSTITUTED HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF DISEASES
TW201406707A (zh) 2012-05-04 2014-02-16 Acucela Inc 用以治療糖尿病性視網膜病變及其他眼部疾病之方法
US9388199B2 (en) * 2012-06-28 2016-07-12 Novartis Ag Pyrrolidine derivatives and their use as complement pathway modulators
ES2648962T3 (es) * 2012-06-28 2018-01-09 Novartis Ag Derivados de pirrolidina y su uso como moduladores de la vía del complemento
MX2014015738A (es) * 2012-06-28 2015-08-06 Novartis Ag Derivados de pirrolidina y su uso como moduladores de la senda del complemento.
WO2014002054A1 (en) * 2012-06-28 2014-01-03 Novartis Ag Pyrrolidine derivatives and their use as complement pathway modulators
RU2515502C1 (ru) * 2012-12-21 2014-05-10 федеральное государственное автономное образовательное учреждение высшего профессионального образования "Московский физико-технический институт (государственный университет) Поверхностно-активный фотосенсибилизатор, представляющий собой бромид 2-{ 4-[(е)-2-(4-этоксифенил)винил]фенокси} -n, n, n-триметилэтаманамина (с-таб)
EP3621945A4 (en) 2017-05-09 2021-03-03 Ambient Photonics, Inc. STYLE DERIVATIVES FOR THE TREATMENT OF THE CNS AND OTHER DISEASES
WO2019103989A1 (en) * 2017-11-22 2019-05-31 Temple University-Of The Commonwealth System Of Higher Education Novel functionalized n,n-dialkylamino phenyl ethers and their method of use
CN110938003B (zh) * 2018-09-25 2022-11-22 新发药业有限公司 一种芬戈莫德盐酸盐的制备方法
CN112920081B (zh) * 2021-02-06 2023-01-31 许昌学院 一种选择性识别次氯酸的荧光探针及其制备方法和应用

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5929117A (en) * 1996-08-12 1999-07-27 Celgene Corporation Immunotherapeutic agents
WO2002050007A2 (en) * 2000-12-21 2002-06-27 Cancer Research Technology Limited Substituted stilbenes, their reactions and anticancer activity
WO2003035008A2 (en) * 2001-10-26 2003-05-01 Oxigene, Inc. Functionalized stilbene derivatives as improved vascular targeting agents
US20050074497A1 (en) * 2003-04-09 2005-04-07 Schultz Clyde L. Hydrogels used to deliver medicaments to the eye for the treatment of posterior segment diseases
USRE38761E1 (en) * 1987-12-24 2005-07-19 Yissum Research Development Company Of The Hebrew University Of Jerusalem Styryl compounds which inhibit EGF receptor protein tyrosine kinase
WO2006002097A2 (en) * 2004-06-18 2006-01-05 University Of Washington Retinal derivatives and methods for the use thereof for the treatment of visual disorders
US20060012866A1 (en) * 2004-07-16 2006-01-19 Ralf Wolleschensky Arrangement for microscopic observation and/or detection and use
WO2006063128A2 (en) * 2004-12-08 2006-06-15 Sirion Therapeutics, Inc. Methods, assays and compositions for treating retinol-related diseases
RU2006133300A (ru) * 2004-02-17 2008-03-27 Президент Энд Феллоуз Оф Гарвард Колледж (Us) Управление течением офтальмологических расстройств, включая дегенерацию желтого пятна

Family Cites Families (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB815211A (en) 1957-08-13 1959-06-17 Bayer Ag Basic ethers
US2566360A (en) * 1948-08-30 1951-09-04 Schering Corp Aminoalkyl ethers of pyridyl alkylene aryl compounds
CH368181A (de) * 1956-11-13 1963-03-31 Geigy Ag J R Verfahren zur Herstellung von N-Aminoalkylderivaten von Azepinen
US3095449A (en) * 1957-08-06 1963-06-25 Bayer Ag 1-(gamma-dimethylaminopropoxy)-2-alkoxy alkenylbenzenes
NL255316A (ru) 1959-08-28
US3746768A (en) * 1970-10-02 1973-07-17 Scm Corp Substituted phenyl ethers and thioethers as insect repellents
GB1433595A (en) * 1972-07-06 1976-04-28 Ici Ltd Alkanolamine derivatives
DE2547524A1 (de) * 1975-10-23 1977-04-28 Bayer Ag Disubstituierte phenolaether des 3-amino-2-hydroxypropans, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
US4569354A (en) 1982-03-22 1986-02-11 Boston University Method and apparatus for measuring natural retinal fluorescence
FR2558158B1 (fr) * 1984-01-13 1986-05-16 Roussel Uclaf Derives de l'indole ethenyl phenol, leurs sels, procede de preparation, application a titre de medicaments, compositions les renfermant et intermediaires
US4861897A (en) * 1987-06-22 1989-08-29 Ortho Pharmaceutical Corporation 2-Aryloxyalkylaminobenzoxazoles and 2-aryloxyalkylaminobenzothiazoles
US5141959A (en) * 1990-09-21 1992-08-25 Bristol-Myers Squibb Company Isoprenoid phospholipase a2 inhibitors and preparations comprising same
JP3163391B2 (ja) * 1995-03-07 2001-05-08 味の素株式会社 スチルベン誘導体及びそれを含有する制癌剤
TW334418B (en) * 1995-03-07 1998-06-21 Ajinomoto Kk Stilbene derivatives and pharmaceutical compositions
US5641750A (en) 1995-11-29 1997-06-24 Amgen Inc. Methods for treating photoreceptors using glial cell line-derived neurotrophic factor (GDNF) protein product
US6878544B2 (en) 1996-04-19 2005-04-12 Neurotech Sa Retinal cell lines with extended life-span and their applications
FR2747690B1 (fr) * 1996-04-19 1998-06-12 Neurotech Sa Lignees immortalisees de cellules retiniennes et leurs applications au traitement de differents troubles primaires ou secondaires ophtalmologiques ou neurologiques
US6090624A (en) 1996-04-19 2000-07-18 Brown University Research Foundation Immortalized retinal cell lines and their applications
AUPO235996A0 (en) 1996-09-16 1996-10-10 Garvan Institute Of Medical Research Method of cell culture
CA2216439A1 (en) 1996-09-25 1998-03-25 Derek Van Der Kooy Pharmaceuticals containing retinal stem cells
US6713300B1 (en) * 1997-02-27 2004-03-30 University Of Utah Research Foundation Nucleic acid and amino acid sequences for ATP-binding cassette transporter and methods of screening for agents that modify ATP-binding cassette transporter
WO1999029279A2 (en) 1997-12-05 1999-06-17 The Board Of Trustees Of The Leland Stanford Junior University Long-term survival and regeneration of central nervous system neurons
ATE402253T1 (de) 1999-01-05 2008-08-15 Aventis Pharma Sa Humane adulte astrozyten, sowie deren herstellung und verwendung
AU6391000A (en) 1999-07-28 2001-02-19 Genentech Inc. Method of preventing the injury or death of retinal cells and treating ocular diseases
EP1107003A1 (en) 1999-12-09 2001-06-13 Trophos Methods for screening compounds active on neurons
US6406840B1 (en) 1999-12-17 2002-06-18 Biomosaic Systems, Inc. Cell arrays and the uses thereof
AU2001251083A1 (en) * 2000-03-31 2001-10-15 Ortho-Mcneil Pharmaceutical, Inc. Method for using 2-aryloxyalkylaminobenzoxazoles and 2-aryloxyalkylaminobenzothiazoles as h3 antagonists
DE10021246A1 (de) 2000-04-25 2001-10-31 Schering Ag Substituierte Benzoesäureamide und deren Verwendung als Arzneimittel
WO2001083714A2 (en) 2000-05-02 2001-11-08 Central Institute For The Deaf Composition and methods for treating photoreceptor degeneration
US20020009713A1 (en) 2000-05-11 2002-01-24 Miller Freda D. Methods for identifying modulators of neuronal growth
US20030032078A1 (en) 2001-01-23 2003-02-13 Board Of Regents, The University Of Texas System Methods and compositions for the treatment of macular and retinal degenerations
DE10141018A1 (de) * 2001-08-22 2003-03-13 Eth Zuerich Eidgenoessische Te Verwendung von negativ geladenen Phospholipiden, sowie Zusammensetzungen umfassend Phospholipide zur Behandlung des Auges
WO2004000302A1 (en) * 2002-06-25 2003-12-31 Raju Gokaraju Ganga Novel resveratrol analogs
EP1551956A4 (en) * 2002-07-12 2006-12-27 Univ Washington METHOD AND SYSTEMS FOR THE EXTENDED IN VITRO CULTURE OF NEURONAL CELLS
BR0317026A (pt) 2002-12-06 2005-10-25 Alcon Inc Mìmicos de superóxido dismutase para o tratamento de distúrbios e doenças oculares
RS20050430A (en) * 2002-12-19 2007-08-03 Pfizer Inc., 2-(1h-indazol-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophtalmic diseases
JP3793759B2 (ja) 2003-03-07 2006-07-05 憲敬 谷水 有孔パネル構体及びその製造方法
CA2521416A1 (en) * 2003-04-02 2004-10-21 Taigen Biotechnology Polyamine compounds for treating chemokine receptor mediated diseases
EP1625112B1 (en) * 2003-05-14 2009-07-22 High Point Pharmaceuticals, LLC Novel compounds for treatment of obesity
WO2005012506A2 (en) 2003-07-30 2005-02-10 Acucela, Inc. Extended primary retinal cell culture and stress models, and methods of use
WO2005025498A2 (en) * 2003-09-08 2005-03-24 Corus Pharma Substituted acetanilides and benzamides for the treatment of asthma and pulmonary inflammation
TW200529812A (en) 2003-12-26 2005-09-16 Chugai Pharmaceutical Co Ltd Benzamide derivatives
US7706863B2 (en) * 2004-01-21 2010-04-27 University Of Washington Methods for assessing a physiological state of a mammalian retina
JP2007525496A (ja) * 2004-02-17 2007-09-06 プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ 黄班変性症を含む眼科疾患の管理
US7566808B2 (en) * 2004-02-17 2009-07-28 President And Fellows Of Harvard College Management of ophthalmologic disorders, including macular degeneration
US20080275134A1 (en) * 2005-02-24 2008-11-06 University Of Washington Methods for Treatment of Retinal Degenerative Disease
US8098907B2 (en) 2005-07-01 2012-01-17 Siemens Corporation Method and system for local adaptive detection of microaneurysms in digital fundus images
WO2007089673A2 (en) 2006-01-26 2007-08-09 Acucela, Inc. Compositions and methods for treatment of ophthalmic diseases and disorders
CN100398624C (zh) 2006-03-24 2008-07-02 大连理工大学 高分子配位接枝的碱土铝酸盐长余辉发光材料及制备方法
AU2008242626B2 (en) * 2007-04-20 2012-04-12 Acucela Inc. Styrenyl derivative compounds for treating ophthalmic diseases and disorders

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE38761E1 (en) * 1987-12-24 2005-07-19 Yissum Research Development Company Of The Hebrew University Of Jerusalem Styryl compounds which inhibit EGF receptor protein tyrosine kinase
US5929117A (en) * 1996-08-12 1999-07-27 Celgene Corporation Immunotherapeutic agents
WO2002050007A2 (en) * 2000-12-21 2002-06-27 Cancer Research Technology Limited Substituted stilbenes, their reactions and anticancer activity
WO2003035008A2 (en) * 2001-10-26 2003-05-01 Oxigene, Inc. Functionalized stilbene derivatives as improved vascular targeting agents
US20050074497A1 (en) * 2003-04-09 2005-04-07 Schultz Clyde L. Hydrogels used to deliver medicaments to the eye for the treatment of posterior segment diseases
RU2006133300A (ru) * 2004-02-17 2008-03-27 Президент Энд Феллоуз Оф Гарвард Колледж (Us) Управление течением офтальмологических расстройств, включая дегенерацию желтого пятна
WO2006002097A2 (en) * 2004-06-18 2006-01-05 University Of Washington Retinal derivatives and methods for the use thereof for the treatment of visual disorders
US20060012866A1 (en) * 2004-07-16 2006-01-19 Ralf Wolleschensky Arrangement for microscopic observation and/or detection and use
WO2006063128A2 (en) * 2004-12-08 2006-06-15 Sirion Therapeutics, Inc. Methods, assays and compositions for treating retinol-related diseases

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