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RU2002133666A - Производные триазола - Google Patents

Производные триазола Download PDF

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Publication number
RU2002133666A
RU2002133666A RU2002133666/04A RU2002133666A RU2002133666A RU 2002133666 A RU2002133666 A RU 2002133666A RU 2002133666/04 A RU2002133666/04 A RU 2002133666/04A RU 2002133666 A RU2002133666 A RU 2002133666A RU 2002133666 A RU2002133666 A RU 2002133666A
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RU
Russia
Prior art keywords
molecular weight
low molecular
substituted
ring
alkyl
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RU2002133666/04A
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English (en)
Inventor
Такахико ТОБЕ (JP)
Такахико ТОБЕ
Такаши СУГАНЕ (JP)
Такаши СУГАНЕ
Ватару ХАМАГУЧИ (JP)
Ватару ХАМАГУЧИ
Итсуро ШИМАДА (JP)
Итсуро ШИМАДА
Кёичи МАЕНО (JP)
Кёичи МАЕНО
Юньи МИЯТА (JP)
Юньи МИЯТА
Такеши СУЗУКИ (JP)
Такеши СУЗУКИ
Атсуюки КОХАРА (JP)
Атсуюки КОХАРА
Такума МОРИТА (JP)
Такума МОРИТА
Тетсу КИМИЗУКА (JP)
Тетсуя КИМИЗУКА
Михаэль АРЛЬТ (DE)
Михаэль АРЛЬТ
Хартмут ГРАЙНЕР (DE)
Хартмут Грайнер
Original Assignee
Мерк Патент ГмбХ (DE)
Мерк Патент Гмбх
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Publication of RU2002133666A publication Critical patent/RU2002133666A/ru

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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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Claims (7)

1. Медицинские композиции, обладающие ингибирующей способностью по отношению к переносчику глицина за счет того, что включают производные триазола, которые описываются приведенной ниже общей формулой (I), или их фармакологически приемлемые соли
Figure 00000001
где символы в формуле принимают следующие значения:
кружок А обозначает (1) ароматическое углеводородное кольцо, которое может быть замещенным,
(2) алифатическое углеводородное кольцо, которое может быть замещенным или конденсированным с бензольным кольцом или гетерокольцом,
(3) пятичленное гетерокольцо, которое может быть замещенным, содержащее один или два атома азота в качестве гетероатомных компонентов кольца, содержащее один атом кислорода или атом серы в качестве другого гетероатома, и которое может быть конденсировано с бензольным кольцом, или
(4) шестичленное гетерокольцо, которое может быть замещенным, содержащее один атом азота в качестве гетероатомного компонента кольца, содержащее один атом кислорода или атом серы в качестве другого гетероатома, и которое может быть конденсировано с бензольным кольцом;
кружок В и кружок D обозначают ароматические углеводородные кольца, которые могут быть замещенными одинаковым или различным образом, алифатические углеводородные кольца, которые могут быть замещенными, или гетерокольца, которые могут быть замещенными;
R обозначает Н, низкомолекулярный галогеноалкил, арил, который может быть замещенным, гетерокольцо, которое может быть замещенным, циклоалкил, который может быть замещенным, или
-[Alk1]m-X-[Alk2]n-Y-R1;
R1 обозначает Н, ОН, циано, арил, который может быть замещенным, гетерокольцо, которое может быть замещенным, циклоалкил, который может быть замещенным, или низкомолекулярную алкоксигруппу;
X обозначает связь, атом кислорода, -S(O)q-, или -N(R2)-;
Y обозначает связь, -С(O)-, -С(O)-N(R3)-, -Z1-Alk3-, или
-N(R3)-Alk3-С(О)-,
где R1 представляет собой группу, отличную от ОН и низкомолекулярных алкоксигрупп в случае, когда Y обозначает связь;
Alk1 и Alk2 могут быть одинаковыми или различными и обозначают низкомолекулярный алкилен, низкомолекулярный алкенилен, или низкомолекулярный алкинилен;
m и n могут быть одинаковыми или различными и равны 0 или 1, причем m+n=1 в случае, когда Х представляет собой связь;
Z1 обозначает -S(O)q-, -N(R3)-, -С(О)- или -С(О)-N(R3)-;
Alk3 обозначает низкомолекулярный алкилен,
R2 и R3 могут быть одинаковыми или различными и обозначают Н или низкомолекулярный алкил, и
q обозначает 0, 1, или 2.
2. Медицинские композиции по п.1, предназначенные для улучшения расстройства обучаемости.
3. Новые производные триазола, выраженные приведенной ниже общей формулой (1а), и
Figure 00000002
их соли,
в этой формуле символы принимают следующие значения:
кружок А' обозначает (1) группу, которая описывается следующей формулой:
Figure 00000003
(2) нафталин, который может быть замещенным одной или двумя группами-заместителями, выбранными из групп, выраженных Rf,
(3) алифатическое углеводородное кольцо, которое может быть замещенным одной или двумя группами-заместителями, выбранными из групп, выраженных Rf, и которое может быть конденсировано с бензольным кольцом, или гетерокольцо,
(4) пятичленное гетерокольцо, которое может быть замещенным одной или двумя группами-заместителями, выбранными из групп, выраженных Rf, содержащее один или два атома азота в качестве гетероатомных компонентов кольца, содержащее один атом кислорода или атом серы в качестве другого гетероатома, и которое может быть конденсировано с бензольным кольцом, или
(5) шестичленное гетерокольцо, которое может быть замещенным одной или двумя группами-заместителями, выбранными из групп, выраженных Rf, содержащее один атом азота в качестве входящего в кольцо гетероатома, содержащее один атом кислорода или атом серы в качестве другого гетероатома, и которое может быть конденсировано с бензольным кольцом;
кружок В' обозначает либо бензол, либо азотсодержащее моноциклическое гетерокольцо;
кружок D' обозначает либо бензол, либо гетерокольцо, причем А', В' и D' не обозначают одновременно бензольные кольца;
Ra обозначает низкомолекулярный галогеноалкил, гетерокольцо, которое может быть замещенным, циклоалкил который может быть замещенным, или -[Alk1]m-X-[Alk2]n-Y-R1;
R1 обозначает Н, ОН, циано, арил, который может быть замещенным, гетерокольцо, которое может быть замещенным, циклоалкил, который может быть замещенным, или низкомолекулярную алкоксигруппу;
X обозначает связь, атом кислорода, -S(O)q-, или -N(R2)-,
Y обозначает связь, -С(О)-, -С(O)-N(R3)-, -Z1-Alk3- или -N(R3)-Alk3-С(О)-,
где в случае, когда Y представляет собой связь, R1 обозначает группу, отличную от ОН и низкомолекулярной алкоксигруппы;
Alk1 и Alk2 могут быть одинаковыми или различными и обозначают низкомолекулярный алкилен, низкомолекулярный алкенилен, или низкомолекулярный алкинилен;
m и n могут быть одинаковыми или различными и равны 0 или 1, при условии, что m+n=1 в случае, когда Х обозначает связь;
Z1 обозначает -S(O)q-, -N(R3)-, -С(О)-, или -С(O)-N(R3)-;
Alk3 обозначает низкомолекулярный алкилен;
R2 и R3 могут быть одинаковыми или различными и обозначают Н или низкомолекулярный алкил;
Rb обозначает атом галогена, низкомолекулярный алкил, который может быть замещенным приведенными ниже группами-заместителями, низкомолекулярный алкинил, низкомолекулярный галогеноалкил, гетерокольцо, гетерокольцо -О-, циано, нитро, низкомолекулярный галогеноалкил -О-, низкомолекулярную алкоксигруппу -О- низкомолекулярный алкилен -N-(R3)- низкомолекулярный алкилен -С(O)O-R6, Z2 - R6, или Z3 - R7, где замещающими группами для низкомолекулярного алкила являются следующие: ОН, циано, низкомолекулярная алкоксигруппа или аминогруппа, которая может быть замещенной низкомолекулярным алкилом;
Z2 -S(O)q-, -N(R3)-, -С(О)-, -С(O)-N(R3)-, -N(R3)-C(О)-, -С(O)-S(O)q-, -N-(R3)-S(O)q-, или -С(О)О-;
Z3 -N(R3) или -N(R3)-C(O)-;
R6 Н, низкомолекулярный алкил или арил;
R7 ОН или низкомолекулярная алкоксигруппа;
p равно 0 или 1;
q равно 0, 1, или 2;
Rc обозначает низкомолекулярный алкил или атом галогена;
Rd и Re могут быть одинаковыми или различными и обозначают Н, атом галогена, низкомолекулярный алкил, низкомолекулярную алкоксигруппу, ОН, галогеноалкил, фенил, низкомолекулярный галогеноалкил-O-, или
-N(R8)-C(О)-R9;
R8 и R9 могут быть одинаковыми или различными и обозначают Н или низкомолекулярный алкил;
Rf обозначает группы, выраженные Rb, оксогруппы, или арил, в котором Rd обозначает группу, отличную от Н, в случае, если кружок В' представляет собой бензол, когда кружок А' обозначает бензол, замещенный низкомолекулярной алкоксигруппой.
4. Производные триазола выраженные приведенной ниже общей формулой (1b), и их соли
Figure 00000004
где символы в формуле принимают следующие значения:
Ra, Re, и p соответствуют определениям, приведенным для соединения формулы (1а), описанного в п.3;
Rb' обозначает атом галогена, низкомолекулярный алкил, который может быть замещенным указанными ниже группами-заместителями, низкомолекулярный галогеноалкил, гетерокольцо, гетерокольцо-O-, циано, нитро, низкомолекулярный галогеноалкил -О-, низкомолекулярную алкоксигруппу, -О- низкомолекулярный алкилен -N(R3)- низкомолекулярный алкилен -С(O)O-R6, -N(R3)-R7, Z2 - R6, или Z3 - R7, где замещающими группами для низкомолекулярного алкила являются следующие: ОН, циано, низкомолекулярная алкоксигруппа, или аминогруппа, которая может быть замещенной низкомолекулярным алкилом;
R, Z3, R6, R7 и q соответствуют определениям, приведенным для соединения формулы (1а), описанного в п.3;
Rd' обозначает Н, низкомолекулярную алкоксигруппу, ОН, или низкомолекулярный алкил,
Re' обозначает Н, атом галогена, низкомолекулярную алкоксигруппу, низкомолекулярный галогеноалкил, низкомолекулярный галогеноалкил-O-, или -N(R8)C(О)-R9;
R8 и R9 обозначают те же группы, которые определены для соединения (1а), описанного в п.3;
где
(1) если Ra обозначает низкомолекулярный алкил, р=0, и Rb' представляет собой низкомолекулярный алкил, низкомолекулярную алкоксигруппу, либо атом галогена, по крайней мере одно из Rd' и Re' обозначает группу, отличную от Н, и Rd' обозначает группу, отличную от низкомолекулярного алкила в случае, когда Re' представляет собой Н,
(2) если Ra обозначает α-стирил, Rd' и Re' обозначают Н, и р=0, Rb' представляет собой группу, отличную от низкомолекулярного алкила и низкомолекулярной алкоксигруппы, и
(3) если Ra обозначает 2-фурил, Rd' и Re' обозначают Н, и р=0, то Rb' представляет собой группу, отличную от низкомолекулярного алкила.
5. Производные триазола по п.3 или их соли, в которых производные триазола, выраженные общей формулой (1а), содержат: азотсодержащее моноциклическое гетерокольцо в качестве кружка В', бензольное кольцо в качестве кружка D', и атом галогена, низкомолекулярный алкил, низкомолекулярную алкоксигруппу, арил, циано, карбамоил или оксогруппу, в качестве Rf.
6. Следующие соединения и их соли: 5-[4-(2,6-дифторфенил)-5-изопропил-4H-1,2,4-триазол-3-ил]-2-фенилпиридин; 4-[3-изопропил-5-(6-фенилпиридин-3-ил)-4H-1,2,4-триазол-4-ил]-2,1,3-бензоксадиазол; 3-[3-(3-метоксипропил)-5-(6-фенилпиридин-3-ил)-4Н-1,2,4-триазол-4-ил]-2 метилбензонитрил; 3-[3-этил-5-(6-фенилпиридин-3-ил)-4Н-1,2,4-триазол-4-ил]-2-метилбензонитрил; 2-{3-[N-(2-метоксиэтил)-N-метиламино]-5-(6-фенилпиридин-3-ил)-4H-1,2,4-триазол-4-ил}бензонитрил; и 4-(2,1,3-бензоксадиазол-4-ил)-N-(2-метоксиэтил)-N-метил-5-(6-фенилпиридин-3-ил)-4Н-1,2,4-триазол-3-ил-амин.
7. Фармацевтические композиции, которые включают производные триазола, описанные в п.3 или 4, в качестве действующего вещества.
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AR030933A1 (es) 2003-09-03
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JP3873746B2 (ja) 2007-01-24
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