RU2019119893A - Ингибиторы jak2 и alk2 и способы их использования - Google Patents

Ингибиторы jak2 и alk2 и способы их использования Download PDF

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RU2019119893A
RU2019119893A RU2019119893A RU2019119893A RU2019119893A RU 2019119893 A RU2019119893 A RU 2019119893A RU 2019119893 A RU2019119893 A RU 2019119893A RU 2019119893 A RU2019119893 A RU 2019119893A RU 2019119893 A RU2019119893 A RU 2019119893A
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alkyl
halogen
alkoxy
compound according
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Алексис МОЛЛАРД
Стивен Л. УОРНЕР
Гэри А. ФЛИНН
Харипрасад ВАНКАЯЛАПАТИ
Дэвид Дж. БИРСС
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Толеро Фармасьютикалз, Инк.
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Claims (41)

1. Соединение, имеющее следующую структуру (I):
Figure 00000001
.
или его стереоизомер, фармацевтически приемлемая соль, таутомер или пролекарство, где:
A обозначает 6-членное ароматическое кольцо или 5- или 6-членное гетероарильное кольцо;
X является -NH-, -О-, -S(О)m-, -CH2-, -CHOH- или -C(=О)-;
R1 является H, галогеном, C1-C6 алкилом, C2-C6 алкенилом, C2-C6 алкинилом, C1-C6 галогеналкилом, C1-C6 алкоксигруппой, -S(О)m C1-C6 алкилом, C1-C6 гидроксиалкилом, -OCH2CH2R9, -(CH2)nNRaRb или -CONRaRb;
R2 является галогеном, C1-C6 алкилом, C2-C6 алкенилом, C2-C6 алкинилом, C1-C6 галогеналкилом, C1-C6 алкоксигруппой, -S(О)m C1-C6 алкилом, C1-C6 гидроксиалкилом, -OCH2CH2R9, -(CH2)nNRaRb или -CONRaRb;
R3 является галогеном, C1-C6 алкилом, C2-C6 алкенилом, C2-C6 алкинилом, C1-C6 галогеналкилом, C1-C6 алкоксигруппой, -S(О)m C1-C6 алкилом, C1-C6 гидроксиалкилом, -OCH2CH2R9, -(CH2)nNRaRb, -CONRaRb или -NHCHRaRb;
R4 является H или C1-C6 алкилом;
R5 в каждом случае наличия независимо является H, галогеном, C1-C6 алкилом, C1-C6 алкоксигруппой, C3-C6 циклоалкоксигруппой, -CN, C1-C6 цианоалкилом или C3-C6 цианоциклоалкилом;
Каждый из R6 и R7 независимо является H, галогеном, гидроксилом, C1-C6 алкилом, C1-C6 алкоксигруппой, C3-C6 циклоалкоксигруппой, C1-C6 цианоалкилом, C3-C6 цианоциклоалкилом, C3-C6 цианоциклоалкилалкилом или -(CH2)nNRaRb;
R8 является H, галогеном, гидроксилом, C1-C6 алкилом, C1-C6 алкоксигруппой, C3-C6 циклоалкоксигруппой, C1-C6 цианоалкилом, C3-C6 цианоциклоалкилом, C3-C6 цианоциклоалкилалкилом, -(CH2)nNRaRb, арилом или гетероарилом;
R9 является -H, -F, -Cl, C1-C4 алкилом, C2-C3 алкенилом, C2-C3 алкинилом, C3-C4 циклоалкилом, -CH2OH, -OCH3, -OCH2CH3, -S(О)mCH3, -CH2CN, -CH2OCH3, -CH2S(О)mCH3, -CN, -CHCH3CN, -C(CH3)2CN или
Figure 00000002
;
Каждый из Ra и Rb независимо является -H, C1-C6 алкилом, C1-C6 гидроксиалкилом, или Ra и Rb образуют необязательно замещенное 5- или 6-членное насыщенное карбоциклическое или гетероциклическое кольцо совместно с атомом азота или углерода, к которому они присоединены;
m равняется 0, 1 или 2;
n равняется 0, 1, 2 или 3; и
z равняется 0, 1 или 2
при условии, что:
Либо R5 не является H, либо ни один заместитель из R6, R7 или R8 не является -CH2CN, когда X является NH, A является 6-членным ароматическим кольцом и один заместитель из R1, R2 или R3 является 4-метилпиперазин-1-илом, а другой заместитель из R1, R2 или R3 является F или CF3; и
C1-C6 алкоксигруппа незамещена гетероциклилом.
2. Соединение по п. 1, в котором соединения имеет следующую структуру (II):
Figure 00000003
,
в которой:
X является -NH-;
Y является Н или CH;
R1 является H или C1-C6 алкоксигруппой;
R2 является галогеном или C1-C6 алкоксигруппой;
R3 является C1-C6 алкоксигруппой или -NHCHRaRb;
R4 является H;
R5 в каждом случае наличия независимо является H, галогеном, C1-C6 алкилом, C1-C6 алкоксигруппой, -CN или C1-C6 цианоалкилом;
Каждый из R6 и R7 независимо является H, галогеном, C1-C6 алкилом, C1-C6 цианоалкилом, C3-C6 цианоциклоалкилом;
R8 является H или гетероарилом; и
z равняется 0, 1 или 2.
3. Соединение по любому из пп. 1 или 2, в котором X является -NH-.
4. Соединение по любому из пп. 1-3, в котором Y является CH.
5. Соединение по любому из пп. 1-3, в котором Y является N.
6. Соединение по любому из пп. 1-5, в котором R1 является H.
7. Соединение по любому из пп. 1-5, в котором R1 является C1-C6 алкоксигруппой.
8. Соединение по п. 7, в котором R1 является метоксигруппой.
9. Соединение по любому из пп. 1-8, в котором R2 является галогеном.
10. Соединение по п. 9, в котором R2 является F или Cl.
RU2019119893A 2013-03-14 2014-03-13 Ингибиторы jak2 и alk2 и способы их использования RU2019119893A (ru)

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