RU2209813C2 - Производные пиридазина, лекарственные средства на их основе и способ лечения артрита - Google Patents

Производные пиридазина, лекарственные средства на их основе и способ лечения артрита Download PDF

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RU2209813C2
RU2209813C2 RU2000115577/04A RU2000115577A RU2209813C2 RU 2209813 C2 RU2209813 C2 RU 2209813C2 RU 2000115577/04 A RU2000115577/04 A RU 2000115577/04A RU 2000115577 A RU2000115577 A RU 2000115577A RU 2209813 C2 RU2209813 C2 RU 2209813C2
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Масао ОХКУТИ
Йосинори КИОТАНИ
Хиромити СИГИО
Томойуки КОСИ
Такахиро Китамура
Такайуки МАТСУДА
Тадааки ОХГИЙА
Йукийоси ЙАМАЗАКИ
Натсуйо КУМАИ
Киоко КОТАКИ
Хидео ЙОСИЗАКИ
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Abstract

Изобретение относится к производным пиридазина общей формулы I, в которой R1 представляет фенильную или пиридильную группу, которая может быть замещена 1-3 заместителями, выбранными из галогена и низших алкоксигрупп; R2 представляет фенильную группу, которая может быть замещена в 4-м положении низшей алкоксигруппой, низшей алкилтиогруппой, низшей алкилсульфинильной или низшей алкилсульфонильной группой и в других положениях 1 или 2 заместителями, выбранными из атомов галогена, низших алкоксильных групп, низших алкилтиогрупп, низших алкилсульфинильных групп и низших алкилсульфонильных групп; R3 представляет атом водорода; низшую алкоксильную группу; галогенированную низшую алкильную группу; низшую циклоалкильную группу; фенильную, пиридильную или фенилоксигруппу, которая может быть замещена 1-3 заместителями, выбранными из атомов галогена, низших алкильных групп, низших алкоксильных групп, карбоксильной группы, низших алкоксикарбонильных групп, нитрогруппы, аминогруппы, низших алкиламиногрупп и низших алкилтиогрупп; незамещенную или замещенную низшей алкильной группой пиперидино, пиперидинильную, пиперазино или морфолиногруппу; незамещенную или замещенную бензильной группой аминокарбонильную группу; низшую алкилкарбонильную группу или незамещенную или замещенную низшей алкилильной группой пиперазинокарбонильную группу; А представляет линейную или разветвленную низшую алкиленовую или низшую алкениленовую группу, имеющую 1-6 атомов углерода; или А может означать одинарную связь, когда R3 представляет низшую циклоалкильную или галогенированную низшую алкильную группу; Х представляет атом кислорода или атом серы; при условии, что исключаются следующие комбинации: R1 и R2 представляют 4-метоксифенильную, Х представляет атом кислорода, А представляет одинарную связь и R3 представляет атом водорода или 2-хлорэтильную группу; или их соли. Указанные соединения являются ингибиторами продуцирования интерлейкина-1-β. Кроме того, объектами изобретения являются лекарственное средство, которое является ингибитором продуцирования интерлейкина-1-β, лекарственное средство для профилактики и лечения артрита и способ лечения артрита. 4 с. и 4 з.п. ф-лы, 4 табл.

Description

Таблицы Т Т Тв

Claims (8)

1. Производные пиридазина общей формулы I
Figure 00000003

в которой R1 представляет фенильную или пиридильную группу, которая может быть замещена 1-3 заместителями, выбранными из атомов галогена и низших алкоксигрупп;
R2 представляет фенильную группу, которая может быть замещена в 4-м положении низшей алкоксигруппой, низшей алкилтиогруппой, низшей алкилсульфинильной группой или низшей алкилсульфонильной группой и в других положениях 1 или 2 заместителями, выбранными из атомов галогена, низших алкоксильных групп, низших алкилтиогрупп, низших алкилсульфинильных групп и низших алкилсульфонильных групп;
R3 представляет атом водорода; низшую алкоксильную группу; галогенированную низшую алкильную группу; низшую циклоалкильную группу; фенильную, пиридильную или фенилоксигруппу, которая может быть замещена 1-3 заместителями, выбранными из атомов галогена, низших алкильных групп, низших алкоксильных групп, карбоксильной группы, низших алкоксикарбонильных групп, нитрогруппы, аминогруппы, низших алкиламиногрупп и низших алкилтиогрупп; незамещенную или замещенную низшей алкильной группой пиперидино, пиперидинильную, пиперазино или морфолиногруппу; незамещенную или замещенную бензильной группой аминокарбонильную группу; низшую алкилкарбонильную группу или незамещенную или замещенную низшей алкильной группой пиперазинокарбонильную группу;
А представляет линейную или разветвленную низшую алкиленовую группу, имеющую от 1 до 6 атомов углерода, или линейную или разветвленную низшую алкениленовую группу, имеющую от 1 до б атомов углерода; или А может также означать одинарную связь, когда R3 представляет низшую циклоалкильную группу или галогенированную низшую алкильную группу;
Х - атом кислорода или атом серы;
при условии, что исключаются следующие комбинации: R1 и R2 представляют 4-метоксифенильную группу, Х представляет атом кислорода, А представляет одинарную связь и R3 представляет атом водорода или 2-хлорэтильную группу,
или их соли.
2. Производные пиридазина по п. 1, которые являются соединениями, представленными следующей формулой (IA)
Figure 00000004

где R4 представляет линейную или разветвленную низшую алкильную или низшую алкенильную группу, низшую циклоалкильную группу или низшую циклоалкилметильную группу;
Х - атом кислорода или атом серы,
или их соли.
3. Производное пиридазина или его соль по п. 1, которое представляет собой 5,6-бис(4-метоксифенил)-2-этил-2Н-пиридазин-3-он, 5,6-бис(4-метоксифенил)-2-метил-2Н-пиридазин-3-он, 5, б-бис(4-метоксифенил)-2-изопропил-2Н-пиридазин-3-он, 5,6-бис(4-метоксифенил)-2-изобутил-2Н-пиридазин-3-он, 2-аллил-5,6-бис(4-метоксифенил)-2Н-пиридазин-3-он, 5,6-бис(4-метоксифенил)-2-циклопропил-2Н-пиридазин-3-он, 5,6-бис(4-метоксифенил)-2-циклопропил-метил-2Н-пиридазин-3-он, 5,6-бис(4-метоксифенил)-2-циклопропилметил-2Н-пиридазин-3-тион, 5,6-бис(4-метоксифенил)-2-циклопентил-2Н-пиридазин-3-он, 5,6-бис(4-метоксифенил)-2-циклопентилметил-2Н-пиридазин-3 -он, 5,6- бис(4-метоксифенил)-2-(4-хлорциннамил)-2Н-пиридазин-3-он, 5-(4-хлорфенил)-6-(4-метилтиофенил)-2-бензил-2Н-пиридазин-3-он, 5,6-бис(4-метоксифенил)-2-бензил-2Н-пиридазин-3-тион или 5,6-бис(3-фтор-4-метоксифенил)-2-этил-2Н-пиридазин-3-он, или его соль.
4. Лекарственное средство, которое является ингибитором продуцирования интерлейкина-1-β, содержащее в качестве активного ингредиента производное пиридазина или его соль по любому из пп. 1-3.
5. Лекарственное средство для профилактики или лечения артрита, содержащее в качестве активного ингредиента производное пиридазина или его соль по любому из пп. 1-3.
6. Производное пиридазина или его соль по любому из пп. 1-3, предназначенное для производства лекарственного средства, представляющего собой ингибитор продуцирования интерлейкина-1β.
7. Производное пиридазина или его соль по любому из пп. 1-3, предназначенное для производства лекарственного средства для профилактики или лечения артрита.
8. Способ лечения артрита, который включает введение пациенту, нуждающемуся в таком лечении, производного пиридазина или его соли по любому из пп. 1-3.
RU2000115577/04A 1997-11-19 1998-11-09 Производные пиридазина, лекарственные средства на их основе и способ лечения артрита RU2209813C2 (ru)

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JP31813397A JP3999861B2 (ja) 1997-11-19 1997-11-19 新規ピリダジン誘導体及びこれを有効成分とする医薬
JP9/318133 1997-11-19
JP9/318132 1997-11-19
JP31813297 1997-11-19

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PT1043317E (pt) 2009-05-11
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EP2017266A1 (en) 2009-01-21
US20050267113A1 (en) 2005-12-01
ES2324126T3 (es) 2009-07-30
CN1279672A (zh) 2001-01-10
ATE428700T1 (de) 2009-05-15
KR100626605B1 (ko) 2006-09-22
DE69840755D1 (de) 2009-05-28
US20070208025A1 (en) 2007-09-06
US20090069332A1 (en) 2009-03-12
CA2307111A1 (en) 1999-05-27
US20070049595A1 (en) 2007-03-01
US20090270399A1 (en) 2009-10-29
US6348468B1 (en) 2002-02-19
AU738595B2 (en) 2001-09-20
HK1032969A1 (en) 2001-08-10
NO20002169L (no) 2000-05-18
US20080119474A1 (en) 2008-05-22
EP1043317A4 (en) 2003-03-05
AU9762698A (en) 1999-06-07
CA2307111C (en) 2009-06-30
ID24166A (id) 2000-07-13
KR20010031880A (ko) 2001-04-16
HUP0100059A2 (hu) 2002-02-28
WO1999025697A1 (fr) 1999-05-27
EP1043317A1 (en) 2000-10-11
TW502025B (en) 2002-09-11
NO316021B1 (no) 2003-12-01
US20040147516A1 (en) 2004-07-29
DK1043317T3 (da) 2009-07-06
HUP0100059A3 (en) 2002-08-28
US20060160804A1 (en) 2006-07-20
NZ504045A (en) 2001-06-29
US20020123496A1 (en) 2002-09-05
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CN1142148C (zh) 2004-03-17
EP1043317B1 (en) 2009-04-15

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