RU2368604C2 - Ингибиторы фосфодиэстеразы 4, включающие n-замещенные аналоги анилина и дифениламина - Google Patents

Ингибиторы фосфодиэстеразы 4, включающие n-замещенные аналоги анилина и дифениламина Download PDF

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RU2368604C2
RU2368604C2 RU2005104819/04A RU2005104819A RU2368604C2 RU 2368604 C2 RU2368604 C2 RU 2368604C2 RU 2005104819/04 A RU2005104819/04 A RU 2005104819/04A RU 2005104819 A RU2005104819 A RU 2005104819A RU 2368604 C2 RU2368604 C2 RU 2368604C2
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Russia
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pyridylmethyl
methoxy
tetrahydrofuranyloxyphenyl
aniline
cyclopentyloxy
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RU2005104819/04A
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English (en)
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RU2005104819A (ru
Inventor
Ричард А. ШУМАХЕР (US)
Ричард А. ШУМАХЕР
Аллен Т. ХОППЕР (US)
Аллен Т. ХОППЕР
Ашок ТЕХИМ (US)
Ашок Техим
Ханс-Юрген Эрнст ХЕСС (US)
Ханс-Юрген Эрнст ХЕСС
Аксел УНТЕРБЕКК (US)
Аксел УНТЕРБЕКК
Эрик КЮСТЕР (US)
Эрик КЮСТЕР
Джр. Уилльям Фредерик БРУБЕЙКЕР (US)
Джр. Уилльям Фредерик БРУБЕЙКЕР
Роберт Ф. ДАНН (US)
Роберт Ф. ДАНН
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Мемори Фармасьютиклз Корпорейшн
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    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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Abstract

Изобретение относится к N-замещенным аналогам анилина и дифениламина, выбранным из 3,4-бисдифторметокси-N-(3-карбоксифенил)-N-(5-(2-хлорпиридилметил))-анилина, 3,4-бисдифторметокси-N-(3-карбоксифенил)-N-(3-(2-хлорпиридилметил))-анилина, 3,4-бисдифторметокси-N-(3-карбоксифенил)-N-(4-(3,5-диметилизоксазолилметил))анилина, 3-циклопентилокси-4-метокси-N-(3-аминокарбонилфенил)-N-(3-пиридилметил))анилин и других соединений, указанных в п.1 формулы изобретения, и к их фармацевтически приемлемым солям в качестве ингибитора активности PDE4 фермента. Соединения могут найти применение для лечения и профилактики заболеваний, опосредованных активностью PDE4 фермента, таких как ухудшение памяти, вызванное нейродегенеративным расстройством, аллергическое или воспалительное заболевание и др. 3 н. и 12 з.п. ф-лы.

Description

Текст описания представлен в факсимильном виде.
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Claims (15)

1. Соединение, выбранное из следующих:
3,4-Бисдифторметокси-N-(3-карбоксифенил)-N-(5-(2-хлорпиридилметил))-анилин,
3,4-Бисдифторметокси-N-(3-карбоксифенил)-N-(3-(2-хлорпиридилметил))-анилин,
3,4-Бисдифторметокси-N-(3-карбоксифенил)-N-(4-(3,5-диметилизоксазолилметил))анилин,
3-Циклопентилокси-4-метокси-N-(3-аминокарбонилфенил)-N-(3-пиридилметил)анилин,
3,4-Бисдифторметокси-N-(3-карбоксифенил)-N-(5-(4-хлорпиридилметил))-анилин,
3,4-Бисдифторметокси-N-(3-карбокси-4-хлорфенил)-N-(3-пиридилметил)-анилин,
3,4-Бисдифторметокси-N-(4-(1-пиррол-1-ил)фенил)-N-(3-пиридилметил)-анилин,
3,4-Бисдифторметокси-N-(3-карбоксифенил)-N-(5-(4-метоксипиридилметил))анилин,
3-Циклопентилокси-4-метокси-N-фенил-N-(3-(2-этоксипиридилметил))-анилин,
3-Циклопентилокси-4-метокси-N-(3-метиламинокарбонилфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(3-(2-гидроксиэтил)-аминокарбонилфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(4-карбоксифенил)-N-(5-(4-хлорпиридилметил))анилин,
3,4-Бисдифторметокси-N-(3-карбоксифенил)-N-(4-(3,5-дихлорпиридилметил))анилин,
3-Циклопентилокси-4-метокси-N-циклогексиланилин,
3-Циклопентилокси-4-гидрокси-N-(3-трет-бутилоксикарбонилфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-гидрокси-N-(3-карбоксифенил)-N-(3-пиридилметил)-анилин,
3-Циклопентилокси-4-метокси-N-(3-трет-бутилоксикарбонилфенил)-N-(3-пиридилметил)анилин,
4-Метокси-3-(R)-тетрагидрофурилокси-N-(3-карбокси-4-хлорфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(3-карбоксифенил)-N-(4-(3-хлорпиридилметил))анилин,
3-Циклопентилокси-4-метокси-N-фенил-N-(4-(3-хлорпиридилметил))-анилин,
4-Метокси-3-(R)-тетрагидрофурилокси-N-(3-карбоксифенил)-N-(4-пиридилметил)анилин,
4-Метокси-3-(R)-тетрагидрофурилокси-N-(3-пиридил)-N-(4-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(4-карбоксифенил)-N-(4-пиридилметил)-анилин,
3-Циклопентилокси-4-метокси-N-(4-карбокси-3-хлорфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(4-карбокси-3-метилфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(4-карбокси-3-фторфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(3-карбокси-4-хлорфенил)-N-(3-пиридилметил))анилин,
3-Циклопентилокси-4-метокси-N-(3-карбокси-4-фторфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(3-карбоксифенил)-N-(4-(3,5-дихлорпиридилметил))анилин,
3-Циклопентилокси-4-метокси-N-(4-карбоксифенил)-N-(4-(3,5-дихлорпиридилметил))анилин,
3-Циклопентилокси-4-метокси-N-(4-карбоксифенил)-N-(4-(3-хлорпиридилметил))анилин,
4-Метокси-3-(R)-тетрагидрофурилокси-N-(4-карбоксифенил)-N-(4-(3,5-дихлорпиридилметил))анилин,
4-Метокси-3-(R)-тетрагидрофурилокси-N-(3-карбоксифенил)-N-(4-(3,5-дихлорпиридилметил))анилин,
3-Циклопентилокси-4-метокси-N-(3-карбокси-4-метоксифенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(3-карбокси-4-метилфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(4-амино-3-карбоксифенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(3-карбокси-4-трифторметилфенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(4-ацетамидо-3-карбоксифенил)-N-(3-пиридилметил)анилин,
3-Циклопентилокси-4-метокси-N-(4-(N,N-бис-(2,4-диметокси)бензил)-аминосульфонилфенил)-N-(3-пиридилметил)анилин,
Метил-N-(3-циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензоат,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-броманилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(N-пиперидилметил)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(N-морфолинометил)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(N,N-диэтиламино)метил)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-5-метилтиоанилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-метилтиоанилин,
N-(3-(2-(Гидрокси)циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-2-аминоизоникотиновая кислота,
N-(3-Гидрокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-(3-(Гидрокси)циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-амино-2-хлорбензойная кислота,
N-(3,4-Бис-дифторметоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-амино-6-метилбензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(5-фтор-3-пиридилметил)-4-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(5-(1,3-диметилпиразолилметил)-3-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-5-трифторметил-3-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-6-трифторметил-3-аминобензойная кислота,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(3-Циклопентокси-4-метоксифенил)-N-(5-фтор-3-пиридилметил)-3-аминобензойная кислота,
N-(3-Циклопентокси-4-метоксифенил)-N-(5-фтор-3-пиридилметил)-4-аминобензойная кислота,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-Циклобутилокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-Циклогексилокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-Циклогептилокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(4-Метокси-3-(4-пиранилокси)фенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-[2,2,2-Бициклооктанил]окси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-Циклопентокси-4-метоксифенил)-N-(2,6-дифторбензил)-3-аминобензойная кислота,
N-(3-Циклопентокси-4-метоксифенил)-N-(4-(3,5-диметилизоксазолил))-3-аминобензойная кислота,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-амино-5-фторбензойная кислота,
N-(3-Циклопентилокси-4-дифторметоксифенил)-N-(3-пиридилметил)-3-амино-5-фторбензойная кислота,
N-(3,4-Бис-дифторметоксифенил)-N-(3-пиридилметил)-3-амино-5-фторбензойная кислота,
N-(3-Циклобутилокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(3-Циклогексилокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(4-Метокси-3-(2-(2-пиридилэтокси))фенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(3,4-Диметоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(3-Этокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(3-Изопропокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(3-Циклопентилокси-4-метоксифенил)-N-(2-(3-пиридилэтил)-3-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-хлор-4-(5-(2Н)-тетразолил)анилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-хлор-4-(5-тетразолил)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(4-(3,5-дихлорпиридил)метил)-4-(5-(2Н)-тетразолил)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-(2Н)-морфолинил)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-N-метил-1-пиперазинил)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(1-пиперазинил)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(N,N-диэтиламино)анилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-метансульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-метансульфониланилин,
N-(3-Циклопропилметокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(5-хлор-3-пиридилметил)-3-аминобензойная кислота,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-фторбензил)-4-аминобензойная кислота,
N-(3-Циклопентилокси-4-дифторметоксифенил)-N-(3-пиридилметил)-4-аминобензойная кислота,
N-(3,4-Диметоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-Этокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(4-Метокси-3-(1-пропил)оксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(4-Метокси-3-(2-пропил)оксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-Циклопропилэтокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(3-Циклобутилметокси-4-метоксифенил)-N-(3-пиридилметил)-3-аминобензойная кислота,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-гидроксиметиланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-гидроксиметиланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-пиперидинил)сульфониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-метилсульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-(2-метилфенил)сульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-фенилсульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-4-фенилсульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-4-метилсульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенио)-N-(3-пиридиметил)-4-(4-фторфенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(4-(3,5-дихлор-пиридилметил)-4-фенилсульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(4-(3,5-дихлор-пиридилметил)-4-метилсульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридидметил)-4-этилсульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(2-фторфенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-метоксифенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-хлорфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-метилсульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-фенилсульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-фенилсульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(5-фтор-3-пиридилметил)-3-(4-фторфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-метилсульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-фенилсульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-хлорфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(2-фторфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(2,4-дифторфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3,4-дифторфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(1,1-диметилэтил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(5-хлор-2-тиенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-тиенил)сульфониламинокарбониланилин,
N-(3,4-Бисдифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-фторфенил)сульфониламинокарбониланилин,
N-(3,4-Бисдифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-фторфенил)сульфониламинокарбониланилин,
N-(3,4-Бисдифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-хлорфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-цианофенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-фторфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(2-тиенил)-сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-фторфенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-цианофенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(2,6-дифторбензил)-4-(4-фторфенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-фторфенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(2,4-дифторфенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3,4-дифторфенил)сульфониламинокарбониланилин,
N-(3-Циклопропилметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3-хлорфенил)сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-фторбензил)-4-(4-фторфенил)сульфониламинокарбониланилин,
N-(3-Циклопропилметокси-4-метоксифенил)-N-(3-пиридилметил)-4-(4-фторфенил)сульфониламинокарбониланилин,
N-(3-Циклопропилметокси-4-метоксифенил)-N-(3-пиридилметил)-4-(3-фторфенил)сульфониламинокарбониланилин,
N-(4-Дифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-этилсульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-дифторметоксифенил)-N-(3-пиридилметил)-4-(3-цианофенил)сульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-дифторметоксифенил)-N-(3-пиридилметил)-4-(4-фторфенил)сульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-дифторметоксифенил)-N-(3-пиридилметил)-4-(3-фторфенил)сульфониламинокарбониланилин,
N-(3-Циклопентилокси-4-дифторметоксифенил)-N-(3-пиридилметил)-4-(3-хлорфенил)сульфониламинокарбониланилин,
N-(3-Этокси-4-метоксифенил)-N-(3-пиридилметил)-4-(2,4-дифторфенил)сульфониламинокарбониланилин,
N-(3,4-Бисдифторметокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-метилсульфониламинокарбониланилин,
N-(3-Циклопропилметокси-4-метоксифенил)-N-(3-пиридилметил)-4-этилсульфониламинокарбониланилин,
N-(3-Этокси-4-метоксифенил)-N-(3-пиридилметил)-4-(4-фторфенил)сульфониламинокарбониланилин,
N-(3-Этокси-4-метоксифенил)-N-(3-пиридилметил)-4-(3-хлорфенил)сульфониламинокарбониланилин,
N-(3-Этокси-4-метоксифенил)-N-(3-пиридилметил)-4-(3,4-дифторфенил)сульфониламинокарбониланилин,
N-(3-Этокси-4-метоксифенил)-N-(3-пиридилметил)-4-(2-тиенил)-сульфониламинокарбониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-циклопентилметилкарбониламиносульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-фторфенил)карбониламиносульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(1-этил-5-метилпиразол-4-ил)карбониламиносульфониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-(4-метилпиперазин-1-ил)сульфониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-3-(4-морфолинил)сульфониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-4-(4-метилпиперазин-1-ил)сульфониланилин,
N-(3-Циклопентилокси-4-метоксифенил)-N-(3-пиридилметил)-4-(4-морфолинил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-(4-метилпиразин-1-ил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-метилпиразин-1-ил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-морфолинил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-3-(4-морфолинил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-этилпиразин-1-ил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-циклогексилпиразин-1-ил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(3,5-диметилпиперазин-1-ил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-(2-пиридил)пиперазин-1-ил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(4-(4-фторфенил)пиперазин-1-ил)сульфониланилин,
N-(4-Метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-(2,5-диметилпиррол-1-ил)сульфониланилин
и их фармацевтически приемлемые соли,
где соединения, которые необязательно являются оптически активными, могут быть в виде их разделенных энантиомеров или их смесей, включая рацемические смеси.
2. Соединение по п.1, которое представляет собой 3-циклопентилокси-4-метокси-N-(3-трет-бутилоксикарбонилфенил)-N-(3-пиридилметил)анилин или его фармацевтически приемлемую соль.
3. Соединение по п.1, которое представляет собой N-(3,4-бис-дифторметоксифенил)-N-(3-пиридилметил)-4-аминобензойную кислоту или ее фармацевтически приемлемую соль.
4. Соединение по п.1, которое представляет собой N-(4-метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(3-пиридилметил)-4-аминобензойную кислоту или ее фармацевтически приемлемую соль.
5. Соединение по п.1, которое представляет собой N-(4-метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(5-фтор-3-пиридилметил)-4-аминобензойную кислоту или ее фармацевтически приемлемую соль.
6. Соединение по п.1, которое представляет собой N-(3-циклобутилокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойную кислоту или ее фармацевтически приемлемую соль.
7. Соединение по п.1, которое представляет собой N-(3,4-диметоксифенил)-N-(3-пиридилметил)-4-аминобензойную кислоту или ее фармацевтически приемлемую соль.
8. Соединение по п.1, которое представляет собой N-(3-этокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойную кислоту или ее фармацевтически приемлемую соль.
9. Соединение по п.1, которое представляет собой N-(3-изопропокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойную кислоту или ее фармацевтически приемлемую соль.
10. Соединение по п.1, которое представляет собой N-(3-циклопропилметокси-4-метоксифенил)-N-(3-пиридилметил)-4-аминобензойную кислоту или ее фармацевтически приемлемую соль.
11. Соединение по п.1, которое представляет собой N-(4-метокси-3-(3R)-тетрагидрофуранилоксифенил)-N-(5-хлор-3-пиридилметил)-3-аминобензойную кислоту или ее фармацевтически приемлемую соль.
12. Соединение по п.1, которое представляет собой N-(3,4-диметоксифенил)-N-(3-пиридилметил)-3-аминобензойную кислоту или ее фармацевтически приемлемую соль.
13. Способ ингибирования активности PDE4 фермента, включающий введение эффективного количества соединения по любому из пп.1-12.
14. Фармацевтическая композиция, обладающая ингибирующим действием в отношении PDE4 фермента, включающая соединение по любому из пп.1-12 и фармацевтически приемлемый носитель.
15. Композиция по п.14, отличающаяся тем, что содержит от 0,1 до 50 мг указанного соединения.
RU2005104819/04A 2002-07-19 2003-07-21 Ингибиторы фосфодиэстеразы 4, включающие n-замещенные аналоги анилина и дифениламина RU2368604C2 (ru)

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