RU2013127611A - Модуляторы глюкагонового рецептора - Google Patents

Модуляторы глюкагонового рецептора Download PDF

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RU2013127611A
RU2013127611A RU2013127611/04A RU2013127611A RU2013127611A RU 2013127611 A RU2013127611 A RU 2013127611A RU 2013127611/04 A RU2013127611/04 A RU 2013127611/04A RU 2013127611 A RU2013127611 A RU 2013127611A RU 2013127611 A RU2013127611 A RU 2013127611A
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optionally substituted
alkyl
pharmaceutically acceptable
acceptable salt
cycloalkyl
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Гэри Эрик ЭСПНИС
Мэри Тереза ДИДЮК
Кевин Джеймс Филипски
Эйнджел ГУЗМАН-ПЕРЕЗ
Джеффри Аллен Пфефферкорн
Бенджамин Доусон Стивенс
Мейхуа Майк Ту
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Abstract

1. Соединение Формулы Iили его фармацевтически приемлемая соль, гдеRпредставляет собой фенил-замещенный гало или трифторметилом;или 6-членную гетероарильную группу, которая, необязательно, конденсирована с (С-С)циклоалкилом, фенилом или 5-6 членным гетероарилом, и где необязательно конденсированная 6-членная гетероарильная группа, необязательно, замещена одним - четырьмя заместителями, где каждый независимо выбирают из гало, -S(O)-(С)алкила, гидрокси, -C(O)NRR, циано, (С-С)алкила, необязательно, замещенного одним - тремя фторами, или (С-С)алкокси, необязательно, замещенного одним - тремя фторами;Rи Rкаждый независимо представляет собой Н или (С-С)алкил;Rпредставляет собой Н;Rпредставляет собой -(СН)СОН;А, А, Аи Акаждый независимо представляет собой CRили N, при условии, что один или два из А, А, Аи Апредставляют собой N и при дополнительном условии, что Аи Аоба не являются N;Rв каждом случае, независимо, представляет собой Н, гало, циано, (С-С)алкил, необязательно, замещенный одним - тремя фторами, или (С-С)алкокси, необязательно замещенный одним - тремя фторами;L представляет собой -CH(R)-X-;X представляет собой NH;Rпредставляет собой (С-С)алкил, который необязательно замещен одним - тремя фторами, гидрокси или метокси; (С-С)циклоалкил, который необязательно замещен одним - двумя (С-С)алкилами, которые необязательно замещены одним - тремя фторами или одним - двумя (С-С)алкилами, и где один - два углерода (С-С)циклоалкила могут быть заменены NH, N(С-С)алкилом, О или S; или (С-С)циклоалкил-(С-С)алкил, где (С-С)циклоалкильная группа упомянутого (С-С)циклоалкил-(С-С)алкила необязательно замещена одним - двумя (С-С)алкилами, которые, необязательно, замещены одним - тр�

Claims (10)

1. Соединение Формулы I
Figure 00000001
или его фармацевтически приемлемая соль, где
R1 представляет собой фенил-замещенный гало или трифторметилом;
или 6-членную гетероарильную группу, которая, необязательно, конденсирована с (С4-С7)циклоалкилом, фенилом или 5-6 членным гетероарилом, и где необязательно конденсированная 6-членная гетероарильная группа, необязательно, замещена одним - четырьмя заместителями, где каждый независимо выбирают из гало, -S(O)2-(С1-3)алкила, гидрокси, -C(O)NRaRb, циано, (С1-С6)алкила, необязательно, замещенного одним - тремя фторами, или (С1-С6)алкокси, необязательно, замещенного одним - тремя фторами;
Ra и Rb каждый независимо представляет собой Н или (С1-С3)алкил;
R2 представляет собой Н;
R3 представляет собой -(СН2)2СО2Н;
А1, А2, А3 и А4 каждый независимо представляет собой CR4 или N, при условии, что один или два из А1, А2, А3 и А4 представляют собой N и при дополнительном условии, что А2 и А3 оба не являются N;
R4 в каждом случае, независимо, представляет собой Н, гало, циано, (С1-С3)алкил, необязательно, замещенный одним - тремя фторами, или (С1-С3)алкокси, необязательно замещенный одним - тремя фторами;
L представляет собой -CH(R5)-X-;
X представляет собой NH;
R5 представляет собой (С1-С6)алкил, который необязательно замещен одним - тремя фторами, гидрокси или метокси; (С3-С7)циклоалкил, который необязательно замещен одним - двумя (С1-С3)алкилами, которые необязательно замещены одним - тремя фторами или одним - двумя (С1-С3)алкилами, и где один - два углерода (С3-С7)циклоалкила могут быть заменены NH, N(С1-С3)алкилом, О или S; или (С3-С7)циклоалкил-(С1-С6)алкил, где (С3-С7)циклоалкильная группа упомянутого (С3-С7)циклоалкил-(С1-С6)алкила необязательно замещена одним - двумя (С1-С3)алкилами, которые, необязательно, замещены одним - тремя фторами;
В1, В2, В3 и В4 каждый независимо представляет собой CR6 или N, при условии, что не больше, чем два из В1, В2, В3 и В4 представляют собой N; и
R6 в каждом случае, независимо представляет собой Н, гало, (С1-С3)алкил, необязательно замещенный одним - тремя фторами, или (С1-С3)алкокси, необязательно замещенный одним - тремя фторами.
2. Соединение по п. 1 или его фармацевтически приемлемая соль, где R5 представляет собой этил, пропил, изопропил, т-бутил, пентил, неопентил, циклопропил, циклобутил, циклопентил, циклогексил или циклопропилметил, где каждый необязательно замещен 1-3 фторами и, где каждый упомянутый циклопропил, циклобутил, циклопентил, циклогексил, необязательно замещен 1-2 метилами.
3. Соединение по п. 1 или его фармацевтически приемлемая соль, где R1 представляет собой 4-фторметилфенил или 4-хлорфенил; и R4 и R6 в каждом случае представляет собой Н.
4. Соединение по п. 3 или его фармацевтически приемлемая соль, где В1 представляет собой N и В2, В3 и В4 каждый представляет собой CR6; В2 представляет собой N и В1, В3 и В4 каждый представляет собой CR6; В1 и В4 каждый представляет собой N и В2 и В3 каждый представляет собой CR6; В2 и В3 каждый представляет собой N и В1 и В4 каждый представляет собой CR6; или В1 и В3 каждый представляет собой N и В2 и В4 каждый представляет собой CR6.
5. Соединение по п. 1 или его фармацевтически приемлемая соль, где А1 представляет собой N и А2, А3 и А4 каждый представляет собой CR4; А2 представляет собой N и А1, А3 и А4 каждый представляет собой CR4; А1 и А4 каждый представляет собой N и А2 и А3 каждый представляет собой CR4; или А1 и А3 каждый представляет собой N и А2 и А4 каждый представляет собой CR4.
6. 3-[(6-{(S)-3-метил-1-[2-(4-трифторметилфенил)пиримидин-5-iл]бутиламино}пиридин-3-карбонил)амино]пропановая кислота или его фармацевтически приемлемая соль.
7. Фармацевтическая композиция, содержащая (i) соединение по п. 1 или его фармацевтически приемлемую соль и (ii) фармацевтически приемлемый эксципиент, разбавитель или носитель.
8. Композиция по п. 7, где упомянутое соединение или упомянутая его фармацевтически приемлемая соль, присутствуют в терапевтически эффективном количестве.
9. Применение соединения по п. 1 или его фармацевтически приемлемой соли при изготовлении медикамента для лечения или отсрочки развития или появления диабета Типа 2 и диабетзависимых расстройств.
10. Применение соединения по п. 1 или его фармацевтически приемлемой соли при изготовлении медикамента для лечения заболевания, состояния или расстройства, модулируемого деактивацией рецептора глюкагона.
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AU2011346670B2 (en) 2015-05-07
JP2014500306A (ja) 2014-01-09
AR084579A1 (es) 2013-05-29
WO2012085745A1 (en) 2012-06-28
US20150094338A1 (en) 2015-04-02
NZ611529A (en) 2015-06-26
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SG191040A1 (en) 2013-08-30
CA2822017C (en) 2015-04-07
BR112013016033A2 (pt) 2018-06-05
UY33824A (es) 2012-07-31
US8809342B2 (en) 2014-08-19
US20140329862A1 (en) 2014-11-06
TW201302706A (zh) 2013-01-16
CN103261165A (zh) 2013-08-21
CA2822017A1 (en) 2012-06-28
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ZA201303950B (en) 2014-07-30

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