RU99128073A - SUBSTITUTED 2- (2,6-DIOXOPIPERIDIN-3-IL) -PHTHALIMIDES AND -1-OXOISOINDOLINS AND METHOD FOR REDUCING THE FNOA LEVELS - Google Patents

SUBSTITUTED 2- (2,6-DIOXOPIPERIDIN-3-IL) -PHTHALIMIDES AND -1-OXOISOINDOLINS AND METHOD FOR REDUCING THE FNOA LEVELS

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RU99128073A
RU99128073A RU99128073/04A RU99128073A RU99128073A RU 99128073 A RU99128073 A RU 99128073A RU 99128073/04 A RU99128073/04 A RU 99128073/04A RU 99128073 A RU99128073 A RU 99128073A RU 99128073 A RU99128073 A RU 99128073A
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hydrogen
carbon atoms
alkyl containing
methyl
independently
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RU99128073/04A
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RU2209207C2 (en
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Джордж У МАЛЛЕР
Дейвид И СТЕРЛИНГ
Роджер Шен-Чу ЧЕН
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Селджин Корпорейшн
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Claims (12)

1. 2,6-Диоксопиперидин, выбранный из группы, состоящей из (а) соединения формулы
Figure 00000001

которой один из Х и Y представляет собой С=0, а другой из Х и Y представляет собой С=0 или СН2;
(1) каждый из R1, R2, R3 и R4 независимо от других представляет собой галогено, алкил, содержащий от 1 до 4 атомов углерода, или алкоксигруппу, содержащую от 1 до 4 атомов углерода, или (2) один из R1, R2, R3 и R4 представляет собой -NHR5, а остальные из R1, R2, R3 и R4 являются водородом;
R5 представляет собой водород или алкил, содержащий от 1 до 8 атомов углерода, или CO-R7-CН(R10)NR8R9;
R6 представляет собой водород или алкил, содержащий от 1 до 8 атомов углерода, бензо, хлоро, или фторо;
R7 представляет собой м-фенилен или п-фенилен или -(CnH2n)-, где n имеет значение от 0 до 4;
каждый из R8 и R9, взятый независимо от другого, представляет собой водород или алкил, содержащий от 1 до 8 атомов углерода, или R8 и R9, взятые вместе, представляют собой тетраметилен, пентаметилен, гексаметилен или -CH2CH2XCH2CH2-, где Х представляет собой -О-, -S- или -NH-;
R10 представляет собой водород, алкил, содержащий от 1 до 8 атомов углерода, или фенил; и
(б) соли присоединения кислоты указанных соединений, которые содержат атом азота, способный протонироваться.1. 2,6-dioxopiperidine selected from the group consisting of (a) a compound of the formula
Figure 00000001

which one of X and Y represents C = 0, and the other of X and Y represents C = 0 or CH 2 ;
(1) each of R 1 , R 2 , R 3 and R 4, independently of the others, is halogen, alkyl containing from 1 to 4 carbon atoms, or an alkoxy group containing from 1 to 4 carbon atoms, or (2) one of R 1 , R 2 , R 3 and R 4 represents —NHR 5 , and the rest of R 1 , R 2 , R 3 and R 4 are hydrogen;
R 5 represents hydrogen or alkyl containing from 1 to 8 carbon atoms, or CO-R 7 —CH (R 10 ) NR 8 R 9 ;
R 6 represents hydrogen or alkyl containing from 1 to 8 carbon atoms, benzo, chloro, or fluoro;
R 7 represents m-phenylene or p-phenylene or - (C n H 2n ) -, where n has a value from 0 to 4;
each of R 8 and R 9 , taken independently of the other, is hydrogen or alkyl containing from 1 to 8 carbon atoms, or R 8 and R 9 taken together are tetramethylene, pentamethylene, hexamethylene or —CH 2 CH 2 XCH 2 CH 2 -, wherein X is —O—, —S— or —NH—;
R 10 represents hydrogen, alkyl containing from 1 to 8 carbon atoms, or phenyl; and
(b) acid addition salts of said compounds which contain a protonated nitrogen atom. 2. Соединение по п.1, в котором каждый из R1, R2, R3 и R4 независимо от других представляет собой галогено, алкил, содержащий от 1 до 4 атомов углерода, или алкоксигруппу, содержащую от 1 до 4 атомов углерода; R6 является водородом, метилом, этилом или пропилом; R7 является м-фениленом или п-фениленом; каждый из R8 и R9, взятый независимо от другого, является водородом или метилом; и R10 является водородом.2. The compound according to claim 1, in which each of R 1 , R 2 , R 3 and R 4 independently of the others represents halogen, alkyl containing from 1 to 4 carbon atoms, or alkoxy group containing from 1 to 4 carbon atoms ; R 6 is hydrogen, methyl, ethyl or propyl; R 7 is m-phenylene or p-phenylene; each of R 8 and R 9 , taken independently of the other, is hydrogen or methyl; and R 10 is hydrogen. 3. Соединение по п.1, в котором каждый из R1, R2, R3 и R4 независимо от других представляет собой галогено, алкил, содержащий от 1 до 4 атомов углерода, или алкоксигруппу, содержащую от 1 до 4 атомов углерода; R6 является водородом, метилом, этилом или пропилом; R7 представляет собой -(СnН2n)-, где n имеет значение от 0 до 4; каждый из R8 и R9, взятый независимо от другого, является водородом или метилом; и R10 является водородом.3. The compound according to claim 1, in which each of R 1 , R 2 , R 3 and R 4 independently of the others represents halogen, alkyl containing from 1 to 4 carbon atoms, or alkoxy group containing from 1 to 4 carbon atoms ; R 6 is hydrogen, methyl, ethyl or propyl; R 7 represents - (C n H 2n ) -, where n has a value from 0 to 4; each of R 8 and R 9 , taken independently of the other, is hydrogen or methyl; and R 10 is hydrogen. 4. Соединение по п. 1, в котором один из R1, R2, R3 и R4 представляет собой -NH2 , а остальные из R1, R2, R3 и R4 являются водородом; R6 является водородом, метилом, этилом или пропилом; R7 является м-фениленом или п-фениленом; каждый из R8 и R9, взятый независимо от другого, является водородом или метилом; и R10 является водородом.4. The compound of claim 1, wherein one of R 1 , R 2 , R 3, and R 4 is —NH 2 , and the rest of R 1 , R 2 , R 3, and R 4 are hydrogen; R 6 is hydrogen, methyl, ethyl or propyl; R 7 is m-phenylene or p-phenylene; each of R 8 and R 9 , taken independently of the other, is hydrogen or methyl; and R 10 is hydrogen. 5. Соединение по п.1, в котором один из R1, R2, R3 и R4 представляет собой -NH2, а остальные из R1, R2, R3 и R4 являются водородом; R6 является водородом, метилом, этилом или пропилом; R7 представляет собой -(CnH2n)-, где n имеет значение от 0 до 4; каждый из R8 и R9, взятый независимо от другого, является водородом или метилом; и R10 является водородом.5. The compound according to claim 1, in which one of R 1 , R 2 , R 3 and R 4 represents —NH 2 , and the rest of R 1 , R 2 , R 3 and R 4 are hydrogen; R 6 is hydrogen, methyl, ethyl or propyl; R 7 represents - (C n H 2n ) -, where n has a value from 0 to 4; each of R 8 and R 9 , taken independently of the other, is hydrogen or methyl; and R 10 is hydrogen. 6. 2,6-Диоксопиперидин, выбранный из группы, состоящей из (а) соединения формулы
Figure 00000002

в которой один из Х и Y представляет собой С=0, а другой из Х и Y представляет собой С=0 или СН2;
(1) каждый из R1, R2, R3 и R4, независимо от других, представляет собой галогено, алкил, содержащий от 1 до 4 атомов углерода, или алкоксигруппу, содержащую от 1 до 4 атомов углерода, или (2) один из R1, R2, R3 и R4 представляет собой -NHR5, а остальные из R1, R2, R3 и R4 являются водородом;
R5 представляет собой водород, алкил, содержащий от 1 до 8 атомов углерода, или CO-R7-CН(R10)NR8R9;
R6 представляет собой алкил, содержащий от 1 до 8 атомов углерода, бензо, хлоро или фторо;
R7 представляет собой м-фенилен или п-фенилен или -(СnН2n)-, где n имеет значение от 0 до 4;
каждый из R8 и R9, взятый независимо от другого, представляет собой водород или алкил, содержащий от 1 до 8 атомов углерода, или R8 и R9, взятые вместе, представляют собой тетраметилен, пентаметилен, гексаметилен или -СН2СН2ХСH2СН2-, где Х представляет собой -О-, -S- или -NH-;
R10 представляет собой водород, алкил, содержащий от 1 до 8 атомов углерода, или фенил; и
(б) соли присоединения кислоты указанных соединений, которые содержат атом азота, способный протонироваться.6. 2,6-dioxopiperidine selected from the group consisting of (a) a compound of the formula
Figure 00000002

in which one of X and Y represents C = 0, and the other of X and Y represents C = 0 or CH 2 ;
(1) each of R 1 , R 2 , R 3, and R 4 , independently of the others, is halogen, alkyl containing from 1 to 4 carbon atoms, or an alkoxy group containing from 1 to 4 carbon atoms, or (2) one of R 1 , R 2 , R 3 and R 4 is —NHR 5 , and the rest of R 1 , R 2 , R 3 and R 4 are hydrogen;
R 5 represents hydrogen, alkyl containing from 1 to 8 carbon atoms, or CO-R 7 —CH (R 10 ) NR 8 R 9 ;
R6 is alkyl containing from 1 to 8 carbon atoms, benzo, chloro or fluoro;
R 7 represents m-phenylene or p-phenylene or - (C n H 2n ) -, where n has a value from 0 to 4;
each of R 8 and R 9 , taken independently of the other, is hydrogen or alkyl containing from 1 to 8 carbon atoms, or R 8 and R 9 taken together are tetramethylene, pentamethylene, hexamethylene or —CH 2 CH 2 XCH 2 CH 2 -, where X is —O—, —S— or —NH—;
R 10 represents hydrogen, alkyl containing from 1 to 8 carbon atoms, or phenyl; and
(b) acid addition salts of said compounds which contain a protonated nitrogen atom. 7. Соединение по п.6, в котором каждый из R1, R2, R3 и R4 независимо от другого представляет собой галогено, алкил, содержащий от 1 до 4 атомов углерода, или алкоксигруппу, содержащую от 1 до 4 атомов углерода, и R6 является метилом, этилом или пропилом.7. The compound according to claim 6, in which each of R 1 , R 2 , R 3 and R 4 independently of the other represents halogen, alkyl containing from 1 to 4 carbon atoms, or alkoxy group containing from 1 to 4 carbon atoms and R 6 is methyl, ethyl or propyl. 8. Соединение по п.6, в котором один из R1, R2, R3 и R4 представляет собой -NH2 , а остальные из R1, R2, R3 и R4 являются водородом, и R6 является метилом, этилом или пропилом.8. The compound according to claim 6, in which one of R 1 , R 2 , R 3 and R 4 represents —NH 2 , and the rest of R 1 , R 2 , R 3 and R 4 are hydrogen, and R 6 is methyl, ethyl or propyl. 9. Способ снижения нежелательных уровней ФHОα у млекопитающего, при котором ему вводят эффективное количество соединения по п.1.9. A method of reducing undesirable levels FHO α in a mammal in which it is administered an effective amount of a compound of claim 1. 10. Способ снижения нежелательных уровней ФHОα у млекопитающего, при котором ему вводят эффективное количество соединения по п.6.10. A method of reducing undesirable levels of PFO α in a mammal, in which he is administered an effective amount of a compound according to claim 6. 11. Фармацевтическая композиция, содержащая соединение по п.1 в количестве, достаточном для снижения уровней ФHОα у млекопитающего при введении в режиме однократной или многократной дозы, в комбинации с носителем.11. A pharmaceutical composition containing the compound according to claim 1 in an amount sufficient to reduce the levels of PFO α in a mammal when administered in a single or multiple dose regimen, in combination with a carrier. 12. Фармацевтическая композиция, содержащая соединение по п.6 в количестве, достаточном для снижения уровней ФHОα у млекопитающего при введении в режиме однократной или многократной дозы, в комбинации с носителем.12. A pharmaceutical composition containing a compound according to claim 6 in an amount sufficient to reduce the levels of PFO α in a mammal when administered in a single or multiple dose regimen in combination with a carrier.
RU99128073A 1997-05-30 1998-05-28 2,6-dioxopiperidine, method for reduction of undesirable levels of tnf-alpha in mammal, pharmaceutical composition RU2209207C2 (en)

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