RU2020110366A - Новые соединения сульфонамидкарбоксамидов - Google Patents

Новые соединения сульфонамидкарбоксамидов Download PDF

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RU2020110366A
RU2020110366A RU2020110366A RU2020110366A RU2020110366A RU 2020110366 A RU2020110366 A RU 2020110366A RU 2020110366 A RU2020110366 A RU 2020110366A RU 2020110366 A RU2020110366 A RU 2020110366A RU 2020110366 A RU2020110366 A RU 2020110366A
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RU2020110366A
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RU2020110366A3 (ru
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Мэтью КУПЕР
Дэвид Миллер
Ангус МАКЛАУД
ВИЛТЕНБУРГ Джимми ВАН
Стивен Том
Стивен СТ-ГАЛЛАЙ
Джонатан ШЭННОН
Томас ЭЙЛАНИН
Стюарт ОНЬОНЗ
Иэн СТРАТ
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Инфлазоум Лимитед
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Priority claimed from GBGB1713082.4A external-priority patent/GB201713082D0/en
Priority claimed from GBGB1718563.8A external-priority patent/GB201718563D0/en
Priority claimed from GBGB1721726.6A external-priority patent/GB201721726D0/en
Priority claimed from GBGB1810983.5A external-priority patent/GB201810983D0/en
Application filed by Инфлазоум Лимитед filed Critical Инфлазоум Лимитед
Publication of RU2020110366A publication Critical patent/RU2020110366A/ru
Publication of RU2020110366A3 publication Critical patent/RU2020110366A3/ru

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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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    • A61K31/41—Heterocyclic 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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    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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Claims (83)

1. Соединение формулы I:
Figure 00000001
,
где Q выбирают из О или S;
R1 представляет собой насыщенную или ненасыщенную гидрокарбильную группу, причем данная гидрокарбильная группа может быть с нормальной или разветвленной цепью, или представляет собой или включает циклические группы, причем гидрокарбильная группа может быть необязательно замещенной, и при том, что гидрокарбильная группа может необязательно содержать один или более гетероатомов N, О или S в своем углеродном скелете; и
R2 представляет собой циклическую группу, замещенную в α-положении одновалентной гетероциклической группой или одновалентной ароматической группой, причем кольцевой атом гетероциклической или ароматической группы непосредственно присоединен к кольцевому атому циклической группы, при этом гетероциклическая или ароматическая группа необязательно может быть замещена, и при том, что циклическая группа необязательно может быть дополнительно замещена.
2. Соединение по п. 1, где R1 представляет собой 4-10-членную циклическую группу, причем данная циклическая группа может необязательно быть замещена.
3. Соединение по п. 1, где R1 представляет собой С1-С15 алкильную, С2-С15 алкенильную или С2-С15 алкинильную группу, все из которых могут необязательно быть замещены, и все из которых могут необязательно содержать один, два или три гетероатома N, О или S в своем углеродном скелете.
4. Соединение по любому одному из пп. 1-3, где R1 замещена одним, двумя или тремя заместителями, независимо выбранными из галогена; -CN; -N3; -Rβ; -ОН; -ORβ; -SO2Rβ; -NH2; -NHRβ; -N(Rβ)2; -Rα-NH2; -Rα-NHRβ; -Rα-N(Rβ)2; -CORβ; -COORβ; -OCORβ; -Rα-CORβ; -Rα-COORβ; -Rα-OCORβ; -CONH2; -CONHRβ; -CON(Rβ)2; или оксо (=O);
где каждую -Rα- независимо выбирают из C1-C6 алкиленовой группы, причем один или два атома углерода в скелете алкиленовой группы могут необязательно быть заменены одним или двумя гетероатомами N, О или S, и при этом данная алкиленовая группа может необязательно быть замещена одним или двумя галогенами и/или группами -Rβ; и
где каждую -Rβ независимо выбирают из С1-С6 алкильной, С2-С6 алкенильной, С2-С6 алкинильной или С2-С6 циклической группой, причем, любая -Rβ может необязательно быть замещена одной, двумя или тремя С1-С4 алкильными, С1-С4 галогеналкильными, С3-С7 циклоалкильными, -O(C1-C4 алкильными), -O(C1-C4 галогеналкильными), -O(С3-С7 циклоалкильными), галогенами, -ОН, -NH2, -CN, -С=СН или оксо (=O) группами.
5. Соединение по любому одному из пп. 1-4, где α-замещенная циклическая группа R2 представляет собой 5- или 6-членную циклическую группу, причем данная циклическая группа может необязательно быть дополнительно замещена.
6. Соединение по любому одному из пп. 1-5, где одновалентная гетероциклическая или ароматическая группа в α-положении данной циклической группы R2 представляет собой фенильную или 5- или 6-членную гетероциклическую группу, все из которых могут необязательно быть замещены.
7. Соединение по любому одному из пп. 1-6, где одновалентная гетероциклическая или ароматическая группа в α-положении данной циклической группы R2 представляет собой фенил, пиридинил, пиримидинил или пиразолил, все из которых могут необязательно быть замещены одним или двумя заместителями, независимо выбранными из галогена, -ОН, -NH2, -CN, С1-С3 алкильной или -O(С1-С3 алкильной) групп.
8. Соединение по любому одному из пп. 1-7, где циклическая группа R2 дополнительно замещена одним или двумя заместителями, независимо выбранными из галогена, -Rδ, -ORδ или -CORδ групп, причем каждую Rδ независимо выбирают из C1-C6 алкильной, С2-С6 алкенильной, С2-С6 алкинильной или С2-С6 циклической группы, и при этом каждая Rδ необязательно дополнительно замещена одной или более группами галогенов.
9. Соединение по любому одному из пп. 1-8, где Q представляет собой О.
10. Соединение, выбранное из группы, состоящей из:
Figure 00000002
Figure 00000003
Figure 00000004
Figure 00000005
Figure 00000006
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
Figure 00000015
Figure 00000016
Figure 00000017
Figure 00000018
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000022
Figure 00000023
Figure 00000024
Figure 00000025
Figure 00000026
11. Фармацевтически приемлемая соль, сольват или пролекарство соединения по любому одному из пп. 1-10.
12. Фармацевтическая композиция, содержащая соединение по любому одному из пп. 1-10, или фармацевтически приемлемую соль, сольват или пролекарство по п. 11, и фармацевтически приемлемый эксципиент.
13. Фармацевтическая композиция по п. 12, отличающаяся тем, что данная фармацевтическая композиция представляет собой фармацевтическую композицию для местного применения.
14. Соединение по любому одному из пп. 1-10 или фармацевтически приемлемая соль, сольват или пролекарство по п. 11, или фармацевтическая композиция по п. 12 или 13 для применения в медицине.
15. Соединение, фармацевтически приемлемая соль, сольват, пролекарство или фармацевтическая композиция по п. 14 для применения в лечении или предотвращении заболевания, расстройства или патологического состояния, причем заболевание, расстройство или патологическое состояние отвечает на ингибирование NLRP3.
16. Соединение, фармацевтически приемлемая соль, сольват, пролекарство или фармацевтическая композиция по п. 14 или 15 для применения в лечении или предотвращении заболевания, расстройства или патологического состояния, причем заболевание, расстройство или патологическое состояние выбирают из:
(i) воспаления;
(ii) аутоиммунного заболевания;
(iii) рака;
(iv) инфекции;
(v) заболевания центральной нервной системы;
(vi) метаболического заболевания;
(vii) сердечно-сосудистого заболевания;
(viii) респираторного заболевания;
(ix) заболевания печени;
(x) заболевания почек;
(xi) глазного заболевания;
(xii) заболевания кожи;
(xiii) лимфатического заболевания;
(xiv) психологического расстройства;
(xv) болезни трансплантат против хозяина;
(xvi) аллодинии; а также
(xvii) любого заболевания, при котором у человека определено наличие зародышевой или соматической немолчащей мутации в NLRP3.
17. Соединение, фармацевтически приемлемая соль, сольват, пролекарство или фармацевтическая композиция по п. 14 или 15 для применения в лечении или предотвращении заболевания, расстройства или патологического состояния, причем заболевание, расстройство или патологическое состояние выбирают из:
(i) криопирин-ассоциированных периодических синдромов (CAPS);
(ii) синдрома Макла-Уэлльса (MWS);
(iii) семейного холодового аутовоспалительного синдрома (FCAS);
(iv) много системно го воспалительного заболевания новорожденных (NOMID);
(v) семейной средиземноморской лихорадки (FMF);
(vi) пиогенного артрита, синдрома гангренозной пиодермы и угрей (PAPA);
(vii) гипериммуноглобулинемии D и синдрома периодической лихорадки (HIDS);
(viii) периодического синдрома, связанного с рецептором фактора некроза опухоли (TNF) (TRAPS);
(ix) системного ювенильного идиопатического артрита;
(x) болезни Стилла у взрослых (AOSD);
(xi) рецидивирующего полихондрита;
(xii) синдрома Шницлера;
(xiii) синдрома Свита;
(xiv) болезни Бехчета;
(xv) антисинтетазного синдрома;
(xvi) дефицита антагониста рецептора интерлейкина 1 (DIRA); а также
(xvii) гаплонедостаточности А20 (НА20).
18. Способ ингибирования NLRP3, включающий применение соединения по любому одному из пп. 1-10 или фармацевтически приемлемой соли, сольвата или пролекарства по п. 11, или фармацевтической композиции по п. 12 или 13 для ингибирования NLRP3.
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