RU2000108431A - Ингибиторы поли(адф-рибоза) полимеразы ("parp"), способы и фармацевтические композиции для лечения повреждения нервной или сердечно-сосудистой ткани - Google Patents

Ингибиторы поли(адф-рибоза) полимеразы ("parp"), способы и фармацевтические композиции для лечения повреждения нервной или сердечно-сосудистой ткани Download PDF

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RU2000108431A
RU2000108431A RU2000108431A RU2000108431A RU2000108431A RU 2000108431 A RU2000108431 A RU 2000108431A RU 2000108431 A RU2000108431 A RU 2000108431A RU 2000108431 A RU2000108431 A RU 2000108431A RU 2000108431 A RU2000108431 A RU 2000108431A
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cancer
damage
disease
diseases
aging
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Дзиа-Хе Ли
Дзие ЗАНГ
Пол Ф. Джексон
Кейт М. Маклин
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Гилфорд Фармасьютикалз Инк.
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Claims (6)

1. Соединение, формулы I
Figure 00000001

или его фармацевтически приемлемые соль, гидрат, пролекарство или их смеси, где Y обозначает алкилгалоген, алкил-CO-G, COG, прямую связь, С= О, О, NR11 или CR8;
G обозначает NR11R16, OR9, SR9 или R10;
Z обозначает О, S или NR11;
X обозначает NR16, О, S, CR12R13, C= O, связь, -CR12= CR13-, -C(R12R13)C(R14R15)-, или R1, R2, R3, R4, R5, R6, R7, R8, R10, R12, R13, R14 или R15 представляют собой независимо водород, галоген, алкилгалоген, гидрокси, С1-С9-алкил с прямой или разветвленной цепью, С2-С9-алкенил с прямой или разветвленной цепью, С3-С8-циклоалкил, С5-С7-циклоалкенил, арил, амино, алкиламино, нитро, нитрозо, карбокси или аралкил;
R9 обозначает водород, гидрокси, С1-С9-алкил с прямой или разветвленной цепью, С2-С9-алкенил с прямой или разветвленной цепью, С3-С8-циклоалкил, С5-С7-циклоалкенил, арил, амино, алкиламино, карбокси или аралкил;
R11 или R16 обозначают независимо водород, галоген, алкилгалоген, гидрокси, С1-С9-алкил с прямой или разветвленной цепью, С2-С9-алкенил с прямой или разветвленной цепью, С3-С8-циклоалкил, С5-С7-циклоалкенил, арил, амино, алкиламино, карбокси или аралкил; и
где указанные группы алкил, алкенил, циклоалкил, циклоалкенил, арил и аралкил независимо замещены одним или несколькими заместителями, выбранными из группы, состоящей из С3-С8-циклоалкила, С5-С7-циклоалкенила, галогена, гидроксила, нитро, трифторметила, C1-6-алкила с прямой или разветвленной цепью, С2-С6-алкенила с прямой или разветвленной цепью, C1-С4-алкокси, С2-С4-алкенилокси, фенокси, бензилокси и арила, имеющего один или несколько заместителей, независимо выбранных из группы, состоящей из водорода, галогена, гидроксила, нитро, трифторметила, C1-6-алкила с прямой или разветвленной цепью, С2-С6-алкенила с прямой или разветвленной цепью, С1-С4-алкокси или С2-С4-алкенилокси, фенокси и бензилокси; и при условии, что, когда Y представляет СН или ССН3 и имеется двойная связь между C1 и С2 и R1-R7 обозначают Н, тогда Х не является О.
2. Соединение по п. 1, где указанное соединение представляет собой (см. графическую часть).
3. Фармацевтическая композиция, включающая терапевтически эффективное количество соединения формулы I по п. 1 и фармацевтически приемлемый носитель.
4. Фармацевтическая композиция по п. 3 в форме раствора, суспензии, эмульсии, капсул, таблеток, биодеградуированного полимера или твердого имплантата.
5. Способ лечения или предотвращения заболевания или нарушения, выбранных из группы, состоящей из повреждения ткани, являющегося результатом повреждения или гибели клеток вследствие некроза или апоптоза, опосредованных нейронами повреждения ткани или заболеваний, повреждения нервной ткани, являющегося результатом ишемии или перфузионного повреждения, неврологических нарушений и нейродегенеративных болезней, таких как периферическая невропатия, вызываемая физическим повреждением или патологическим состоянием, травматическое повреждение мозга, физическое повреждение спинного мозга, удар, связанный с повреждением мозга, демиелинирующее заболевание и неврологические нарушения, относящиеся к нейродегенерации, такие как болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и латеральный амиотрофический склероз; васкулярного удара, сердечно-сосудистых нарушений, таких как, заболевание венечной артерии, инфаркт миокарда, стенокардия, кардиогенный шок и повреждение сердечно-сосудистой ткани; связанной с возрастом дегенерации желтого пятна, СПИДа и других иммунных заболеваний старения, артрита, атеросклероза, кахексии, рака, такого как АСТН-продуцирующая опухоль, острая лимфоцитарная лейкемия, острый нелимфоцитарный лейкоз, рак коры надпочечника, рак мочевого пузыря, рак мозга, рак молочной железы, рак шейки матки, хронический лимфоцитарный лейкоз, хронический миелоидный лейкоз, колоректальный рак, кожная Т-клеточная лимфома, эндометриальный рак, рак пищевода, саркома Эвинга, рак желчного пузыря, рак "волосатых" клеток (клеток лейкозного ретикулоэндотелиоза), рак головы и шеи, лимфома Ходжкина, саркома Капоши, рак почки, рак печени, рак легкого (мелко-клеточного и/или немелкоклеточного), злокачественный перитонеальный выпот, злокачественный плевральный выпот, меланома, мезотелиома, множественная миелома, нейробластома, неходжкинская лимфома, остеосаркома, овариальный рак, рак яичника (половых клеток), рак предстательной железы, рак поджелудочной железы, рак полового члена, ретинобластома, рак кожи, саркома мягких тканей, плоскоклеточные карциномы, рак желудка, тестикулярный рак, рак щитовидной железы, трофобластный неоплазм, рак матки, рак влагалища, рак вульвы и опухоль Вилма; дегенеративных заболеваний скелетной мышцы, включающих в себя репликационное старение, диабет, травму головы, иммунное старение, воспаление, воспалительные болезни желудочно-кишечного тракта, такие как колиты и болезнь Крона, мышечную дистрофию, остеоартрит, остеопороз, синдром хронической боли, острую боль, невропатическую боль, нервный инсульт, повреждение периферических нервов, почечную недостаточность, ретинальную ишемию, септический шок, такой как эндоксический шок, старение кожи; заболевания или нарушения, связанного с продолжительностью жизни или пролиферативной способностью клеток; заболеваний или нарушений, модифицированных радиосенсибилизацией опухолевых клеток, модифицированных изменением экспрессии генов стареющих клеток и заболеваний или патологических состояний, индуцируемых или обостряемых клеточным старением, включающий назначение композиции по п. 3 субъекту, нуждающемуся в таком лечении или профилактике.
6. Соединение по п. 1, используемое для получения лекарственного средства для лечения и предотвращения заболевания или нарушения, выбранных из группы, состоящей из повреждения ткани, являющегося результатом повреждения или гибели клеток вследствие некроза или апоптоза, опосредованных нейронами повреждения ткани или заболеваний, повреждения нервной ткани, являющегося результатом ишемии или перфузионного повреждения, неврологических нарушений и нейродегенеративных болезней, таких как периферическая невропатия, вызываемая физическим повреждением или патологическим состоянием, травматическое повреждение мозга, физическое повреждение спинного мозга, удар, связанный с повреждением мозга, демиелинирующее заболевание и неврологические нарушения, относящиеся к нейродегенерации, такие как болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и латеральный амиотрофический склероз; васкулярного удара, сердечно-сосудистых нарушений, таких как, заболевание венечной артерии, инфаркт миокарда, стенокардия, кардиогенный шок и повреждение сердечно-сосудистой ткани; связанной с возрастом дегенерации желтого пятна, СПИДа и других иммунных заболеваний старения, артрита, атеросклероза, кахексии, рака, такого как АСТН-продуцирующая опухоль, острая лимфоцитарная лейкемия, острый нелимфоцитарный лейкоз, рак коры надпочечника, рак мочевого пузыря, рак мозга, рак молочной железы, рак шейки матки, хронический лимфоцитарный лейкоз, хронический миелоидный лейкоз, колоректальный рак, кожная Т-клеточная лимфома, эндометриальный рак, рак пищевода, саркома Эвинга, рак желчного пузыря, рак "волосатых" клеток (клеток лейкозного ретикулоэндотелиоза), рак головы и шеи, лимфома Ходжкина, саркома Капоши, рак почки, рак печени, рак легкого (мелкоклеточного и/или немелкоклеточного), злокачественный перитонеальный выпот, злокачественный плевральный выпот, меланома, мезотелиома, множественная миелома, нейробластома, неходжкинская лимфома, остеосаркома, овариальный рак, рак яичника (половых клеток), рак предстательной железы, рак поджелудочной железы, рак полового члена, ретинобластома, рак кожи, саркома мягких тканей, плоскоклеточные карциномы, рак желудка, тестикулярный рак, рак щитовидной железы, трофобластный неоплазм, рак матки, рак влагалища, рак вульвы и опухоль Вилма; дегенеративных заболеваний скелетной мышцы, включающих в себя репликационное старение, диабет, травму головы, иммунное старение, воспаление, воспалительные болезни желудочно-кишечного тракта, такие как колиты и болезнь Крона, мышечную дистрофию, остеоартрит, остеопороз, синдром хронической боли, острую боль, невропатическую боль, нервный инсульт, повреждение периферических нервов, почечную недостаточность, ретинальную ишемию, септический шок, такой как эндоксический шок, старение кожи; заболевания или нарушения, связанного с продолжительностью жизни или пролиферативной способностью клеток; заболеваний или нарушений, модифицированных радиосенсибилизацией опухолевых клеток, модифицированных изменением экспрессии генов стареющих клеток и заболеваний или патологических состояний, индуцируемых или обостряемых клеточным старением.
RU2000108431A 1997-09-03 1998-09-02 Ингибиторы поли(адф-рибоза) полимеразы ("parp"), способы и фармацевтические композиции для лечения повреждения нервной или сердечно-сосудистой ткани RU2000108431A (ru)

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