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RU2008115434A - Новые производные флороглюцина, обладающие активностью в отношении лиганда селектина - Google Patents

Новые производные флороглюцина, обладающие активностью в отношении лиганда селектина Download PDF

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RU2008115434A
RU2008115434A RU2008115434/04A RU2008115434A RU2008115434A RU 2008115434 A RU2008115434 A RU 2008115434A RU 2008115434/04 A RU2008115434/04 A RU 2008115434/04A RU 2008115434 A RU2008115434 A RU 2008115434A RU 2008115434 A RU2008115434 A RU 2008115434A
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Эвальд М. АИДТ (DE)
Эвальд М. АИДТ
Ремо КРАНИХ (DE)
Ремо КРАНИХ
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Abstract

1. Фармацевтические композиции, включающие в себя, по меньшей мере, одно соединение формулы (I) и фармацевтически приемлемый носитель, который является пригодным в медицине, ! ! где символы и заместители имеют нижеследующие значения: ! -Х- представляет собой ! (а) ! ! где m равно 0, 1; n равно целому числу от 1 до 3; ! (b) ! ! где «кольцо» представляет собой ! ! в котором R1 представляет собой Н, NO2, CF3, F, Cl, Br, I, CN, CH3, NH2, NHалкил, NHарил, NНацил и k равно 0, 1; ! (с) ! ! где Т представляет собой О, S или [H,H]; р равно 0, 1, 2; ! -Y- представляет собой ! (а) ! ! где s равно 0 или 1, ! R2 представляет собой CO2H, CO2алкил, CO2арил, CO2NH2, CO2аралкил, SO3H, SO2NH2, PO(OH)2, 1-H-тетразолил-, CHO, COCH3, CH2OH, NH2, NHалкил, N(алкил)алкил', OCH3, CH2OCH3, SH, F, Cl, Br, I, CH3, CH2CH3, CN, CF3; ! R3 независимо от R2 представляет собой H, CH3, CH2CH3, CF3, F, Cl, Br, I, CN, NO2 и ! R4 независимо от R2 и R3 представляет собой H, CH3, CH2CH3, CF3, F, Cl, Br, I, CN, NO2, R2, ! R5 представляет собой H, NO2, CF3, F, Cl, Br, I, CN, CH3, OCH3, SH, NH2 ! и -W- представляет собой -(CH2-)V, цис-СН=СН- или транс-СН=СН-, где v равно 0, 1, 2, ! в случае, когда -W- представляет собой цис-CH=CH- или транс-CH=CH-, R2 не должен быть NH2 или SH; ! (b) ! ! где R6 независимо от R2 представляет собой Н, F, Cl, Me, трет-Bu, CN, NH2; ! (c) ! ! (е) ! ! где t равно 0, 1, 2; ! -Z представляет собой ! (i) ! ! R7 независимо от R2 представляет собой H, NO2, CF3, F, Cl, Br, I, CN, CH3, OCH3, SH, NH2, ! (iv) ! ! где K представляет собой NH, NMe, O, S, ! (v) ! ! или фармацевтически приемлемые соли, сложные эфиры или амиды и пролекарства вышеуказанных соединений формулы (I). ! 2. Фармацевтические композиции по п.1, где соединения имеют формулу (II) ! ! где -X'- представляет собой Х(а) или Х(b) и -Y имеет значения, указанные в п.1. ! 3. Фармацевтические композиции по п.2, где соединения имеют формулу (А) или (В) ! ! где -Х'- и -Y имеют значения, указанные в п.2, и гд�

Claims (12)

1. Фармацевтические композиции, включающие в себя, по меньшей мере, одно соединение формулы (I) и фармацевтически приемлемый носитель, который является пригодным в медицине,
Figure 00000001
где символы и заместители имеют нижеследующие значения:
-Х- представляет собой
(а)
Figure 00000002
где m равно 0, 1; n равно целому числу от 1 до 3;
(b)
Figure 00000003
где «кольцо» представляет собой
Figure 00000004
в котором R1 представляет собой Н, NO2, CF3, F, Cl, Br, I, CN, CH3, NH2, NHалкил, NHарил, NНацил и k равно 0, 1;
(с)
Figure 00000005
где Т представляет собой О, S или [H,H]; р равно 0, 1, 2;
-Y- представляет собой
(а)
Figure 00000006
где s равно 0 или 1,
R2 представляет собой CO2H, CO2алкил, CO2арил, CO2NH2, CO2аралкил, SO3H, SO2NH2, PO(OH)2, 1-H-тетразолил-, CHO, COCH3, CH2OH, NH2, NHалкил, N(алкил)алкил', OCH3, CH2OCH3, SH, F, Cl, Br, I, CH3, CH2CH3, CN, CF3;
R3 независимо от R2 представляет собой H, CH3, CH2CH3, CF3, F, Cl, Br, I, CN, NO2 и
R4 независимо от R2 и R3 представляет собой H, CH3, CH2CH3, CF3, F, Cl, Br, I, CN, NO2, R2,
R5 представляет собой H, NO2, CF3, F, Cl, Br, I, CN, CH3, OCH3, SH, NH2
и -W- представляет собой -(CH2-)V, цис-СН=СН- или транс-СН=СН-, где v равно 0, 1, 2,
в случае, когда -W- представляет собой цис-CH=CH- или транс-CH=CH-, R2 не должен быть NH2 или SH;
(b)
Figure 00000007
где R6 независимо от R2 представляет собой Н, F, Cl, Me, трет-Bu, CN, NH2;
(c)
Figure 00000008
(е)
Figure 00000009
где t равно 0, 1, 2;
-Z представляет собой
(i)
Figure 00000010
R7 независимо от R2 представляет собой H, NO2, CF3, F, Cl, Br, I, CN, CH3, OCH3, SH, NH2,
(iv)
Figure 00000011
где K представляет собой NH, NMe, O, S,
(v)
Figure 00000012
или фармацевтически приемлемые соли, сложные эфиры или амиды и пролекарства вышеуказанных соединений формулы (I).
2. Фармацевтические композиции по п.1, где соединения имеют формулу (II)
Figure 00000013
где -X'- представляет собой Х(а) или Х(b) и -Y имеет значения, указанные в п.1.
3. Фармацевтические композиции по п.2, где соединения имеют формулу (А) или (В)
Figure 00000014
где -Х'- и -Y имеют значения, указанные в п.2, и где -X”- представляет собой
Figure 00000015
и где -Y' представляет собой
Figure 00000016
где все индексы, символы и заместители имеют значения, указанные в п.1.
4. Фармацевтические композиции по п.3, где соединения имеют формулу С
Figure 00000017
где -X”- и -Y' имеют значения, указанные в п.3.
5. Фармацевтические композиции по п.4, где соединения имеют формулу (D)
Figure 00000018
где -Х”- имеет значения, указанные в п.3, и -Y” представляет собой
Figure 00000019
где R9 представляет собой CO2H, CO2алкил, CO2арил, CO2NH2, CO2аралкил, СН2SO3H, СН2SO2NH2, СН2PO(OH)2, 1-H-тетразолил, CHO, COCH3, CH2OH, СН2NH2, СН2NHалкил, СН2N(алкил)алкил', CH2OCH3, СН2SH,
где все индексы, символы и заместители имеют значения, указанные в п.1.
6. Химические соединения, имеющие общую структуру формулы (С) или (D) по п. 4 или 5.
7. Применение соединений, имеющих структуру формулы (I) по п.1, для получения лекарственного средства для лечения хронического обструктивного заболевания легких (COPD), острого повреждения легких (ALI), при экстракорпоральном кровообращении, для лечения острого респираторного дистресс-синдрома (ARDS), болезни Крона, септического шока, сепсиса, хронических воспалительных заболеваний, таких как псориаз, атопический дерматит и ревматоидный артрит, и реперфузионного повреждения, которое имеет место после сердечных приступов, мозговых кровоизлияний, атеросклероза и трансплантации органов, травматического шока, недостаточности деятельности многих органов, аутоиммунных заболеваний, подобных рассеянному склерозу, при подкожной внутрипросветной ангиопластике, для лечения астмы и воспалительного заболевания кишечника.
8. Применение соединений, имеющих структуру формулы (I) по п.1, для получения лекарственного средства для лечения, диагностики или профилактики воспалительных нарушений.
9. Применение соединений, имеющих структуру формулы (I) по п.1, для получения наполнителя для доставки лекарственного средства к органу-мишени при диагностике или терапии.
10. Применение соединений, имеющих структуру формулы (I) по п.1, для получения косметической или дерматологической композиции.
11. Косметические композиции, включающие в себя, по меньшей мере, одно соединение формулы (I) по п.1 и, по меньшей мере, один косметически переносимый компонент.
12. Дерматологические композиции, включающие в себя, по меньшей мере, одно соединение формулы (I) по п.1 и, по меньшей мере, один дерматологически переносимый компонент.
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