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RU2020110394A - Новые соединения сульфонамидкарбоксамидов - Google Patents

Новые соединения сульфонамидкарбоксамидов Download PDF

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RU2020110394A
RU2020110394A RU2020110394A RU2020110394A RU2020110394A RU 2020110394 A RU2020110394 A RU 2020110394A RU 2020110394 A RU2020110394 A RU 2020110394A RU 2020110394 A RU2020110394 A RU 2020110394A RU 2020110394 A RU2020110394 A RU 2020110394A
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RU2020110394A
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RU2020110394A3 (ru
Inventor
Дэвид Миллер
Ангус МАКЛАУД
ВИЛТЕНБУРГ Джимми ВАН
Стивен Том
Стивен СТ-ГАЛЛАЙ
Джонатан ШЭННОН
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Инфлазоум Лимитед
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Priority claimed from GBGB1713079.0A external-priority patent/GB201713079D0/en
Priority claimed from GBGB1713082.4A external-priority patent/GB201713082D0/en
Priority claimed from GBGB1713083.2A external-priority patent/GB201713083D0/en
Priority claimed from GBGB1718561.2A external-priority patent/GB201718561D0/en
Priority claimed from GBGB1718563.8A external-priority patent/GB201718563D0/en
Priority claimed from GBGB1718564.6A external-priority patent/GB201718564D0/en
Priority claimed from GBGB1721726.6A external-priority patent/GB201721726D0/en
Priority claimed from GBGB1810983.5A external-priority patent/GB201810983D0/en
Priority claimed from GBGB1812225.9A external-priority patent/GB201812225D0/en
Application filed by Инфлазоум Лимитед filed Critical Инфлазоум Лимитед
Publication of RU2020110394A publication Critical patent/RU2020110394A/ru
Publication of RU2020110394A3 publication Critical patent/RU2020110394A3/ru

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/52—Y being a hetero atom
    • C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
    • C07C311/55—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to acyclic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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    • A61P35/00—Antineoplastic agents
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    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/52—Y being a hetero atom
    • C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
    • C07C311/57—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/58—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings having nitrogen atoms of the sulfonylurea groups bound to hydrogen atoms or to acyclic carbon atoms
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    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/24—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by sulfur atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • C07D211/58—Nitrogen atoms attached in position 4
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
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    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D213/62—Oxygen or sulfur atoms
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Claims (122)

1. Соединение формулы I:
Figure 00000001
где Q выбирают из О или S;
L представляет собой насыщенную или ненасыщенную С1-С12 гидрокарбиленовую группу, причем данная гидрокарбиленовая группа может быть с нормальной или разветвленной цепью, или представлять собой, или включать в себя циклические группы, при этом данная гидрокарбиленовая группа может необязательно быть замещена, и при том, что данная гидрокарбиленовая группа может необязательно содержать один или более гетероатомов N, О или S в своем углеродном скелете;
R1 представляет собой -NR3R4, -OR5, -(C=NR6)R7, -(CO)R8, -CN, -N3, четвертичную аммониевую группу или необязательно замещенный гетероцикл;
R3, R4, R5, R6, R7 и R8, каждая независимо, представляют собой водород или насыщенную или ненасыщенную C1-С10 гидрокарбильную группу, причем данная гидрокарбильная группа может быть с нормальной или разветвленной цепью, или представлять собой, или включать в себя циклические группы, причем данная гидрокарбильная группа может необязательно быть замещена, и при этом гидрокарбильная группа может необязательно содержать один или более гетероатомов N, О или S в своем углеродном скелете;
причем необязательно L и R3, или L и R4, или R3 и R4 вместе с атомом азота, к которому они присоединены, могут образовывать 3-12-членную насыщенную или ненасыщенную циклическую группу, причем данная циклическая группа может необязательно быть замещена;
причем необязательно L и R5 вместе с атомом кислорода, к которому они присоединены, могут образовывать 3-12-членную насыщенную или ненасыщенную циклическую группу, причем данная циклическая группа может необязательно быть замещена;
причем необязательно L и R6, или L и R7, или R6 и R7 вместе с группой -(C=N)-, к которой они присоединены, могут образовывать 3-12-членную насыщенную или ненасыщенную циклическую группу, причем данная циклическая группа может необязательно быть замещена;
причем необязательно L и R8 вместе с группой -(С=O)-, к которой они присоединены, могут образовывать 3-12-членную насыщенную или ненасыщенную циклическую группу, причем данная циклическая группа может необязательно быть замещена;
R2 представляет собой циклическую группу, замещенную в α-положении, причем R2 может быть необязательно дополнительно замещена.
при условии, что атом группы L, который присоединен к атому серы группы сульфонилмочевины, представляет собой атом углерода и не представляет собой кольцевой атом гетероциклической или ароматической группы.
2. Соединение по п. 1, где L представляет собой насыщенную или ненасыщенную C1-C8 гидрокарбиленовую группу, причем данная гидрокарбиленовая группа может быть с нормальной или разветвленной цепью, или представлять собой, или включать в себя циклические группы, и при этом данная гидрокарбиленовая группа может необязательно быть замещена одним или более заместителями, независимо выбранными из галогена, -CN, -N(R9)2, -OR9 или оксо (=O) групп, где R9 независимо выбирают из атома водорода или C1-С3 алкильной группы.
3. Соединение по п. 1 или 2, где атом группы L, который присоединен к атому серы группы сульфонилмочевины, представляет собой атом углерода и не представляет собой кольцевой атом любой циклической группы.
4. Соединение по любому одному из пп. 1-3, где R1 представляет собой -NR3R4, и R3 и R4, каждая независимо, представляют собой водород или C1-С6 алкильную, С2-С6 алкенильную, С2-С6 алкинильную, C1-С6 циклоалкильную, фенильную или бензильную группу, каждая из которых может необязательно быть замещена одним или более заместителями, независимо выбранными из галогена, -CN, -N(R9)2, -OR9 или оксо (=O) групп, где R9 независимо выбирают из атома водорода или С1-С3 алкильной группы.
5. Соединение по любому одному из пп. 1-3, где R1 представляет собой -OR5, и R5 представляет собой водород или C1-C6 алкильную, C2-C6 алкенильную, С2-С6 алкинильную, C1-C6 циклоалкильную, фенильную или бензильную группу, каждая из которых может необязательно быть замещена одним или более заместителями, независимо выбранными из галогена, -CN, -N(R9)2, -OR9 или оксо (=O) групп, где R9 независимо выбирают из атома водорода или С1-С3 алкильной группы.
6. Соединение по любому одному из пп. 1-3, где R1 представляет собой -(C=NR6)R7, и R6 и R7, каждая независимо, представляют собой водород или C1-C6 алкильную, С2-С6 алкенильную, С2-С6 алкинильную, C1-C6 циклоалкильную, фенильную или бензильную группу, каждая из которых может необязательно быть замещена одним или более заместителями, независимо выбранными из галогена, -CN, -N(R9)2, -OR9 или оксо (=O) групп, где R9 независимо выбирают из атома водорода или С1-С3 алкильной группы.
7. Соединение по любому одному из пп. 1-3, где R1 представляет собой -(CO)R8, и R8 представляет собой водород или С1-С6 алкильную, С2-С6 алкенильную, С2-С6 алкинильную, С1-С6 циклоалкильную, фенильную или бензильную группу, каждая из которых может необязательно быть замещена одним или более заместителями, независимо выбранными из галогена, -CN, -N(R9)2, -OR9 или оксо (=O) групп, где R9 независимо выбирают из атома водорода или С1-С3 алкильной группы.
8. Соединение по любому одному из пп. 1-3, где R1 представляет собой -(CO)R8 и, L и R8 вместе с группой -(С=O)-, к которой они присоединены, образуют 4-, 5- или 6-членную насыщенную циклическую группу, причем данная циклическая группа может необязательно содержать один дополнительный гетероатом N, О или S в своем углеродном скелете, и при этом данная циклическая группа может необязательно быть замещена одним или более заместителями, независимо выбранными из галогена, -CN, -N(R9)2, -OR9, С1-С3 алкильной, С1-С3 алкиленовой или оксо (=O) групп, где R9 независимо выбирают из атома водорода или С1-С3 алкильной группы.
9. Соединение по любому одному из пп. 1-8, где R2 представляет собой арильную или гетероарильную группу, причем арильная или гетероарильная группа замещена в α-положении, и при том, что R2 может быть необязательно дополнительно замещена.
10. Соединение по п. 9, где R2 представляет собой арильную или гетероарильную группу, причем арильная или гетероарильная группа замещена в α- и α'-положениях, и при том, что R2 может быть необязательно дополнительно замещена.
11. Соединение по п. 10, где R2 представляет собой конденсированную арильную или конденсированную гетероарильную группу, причем первое циклоалкильное, циклоалкенильное, неароматическое гетероциклическое, арильное или гетероарильное кольцо конденсировано с арильной или гетероарильной группой в α,β-положениях, а второе циклоалкильное, циклоалкенильное, неароматическое гетероциклическое, арильное или гетероарильное кольцо конденсировано с арильной или гетероарильной группой в α',β'-положениях, и при том, что R2 может быть необязательно дополнительно замещена.
12. Соединение по любому одному из пп. 1-8, где 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 α-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.
13. Соединение по любому одному из пп. 1-8, где R2 представляет собой циклическую группу, замещенную в α- и α'-положениях, причем R2 может быть необязательно дополнительно замещена.
14. Соединение по любому одному из пп. 1-13, где Q представляет собой О.
15. 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
Figure 00000027
Figure 00000028
Figure 00000029
Figure 00000030
Figure 00000031
Figure 00000032
Figure 00000033
Figure 00000034
Figure 00000035
Figure 00000036
Figure 00000037
Figure 00000038
Figure 00000039
Figure 00000040
Figure 00000041
Figure 00000042
Figure 00000043
Figure 00000044
Figure 00000045
Figure 00000046
Figure 00000047
Figure 00000048
Figure 00000049
Figure 00000050
Figure 00000051
Figure 00000052
Figure 00000053
Figure 00000054
Figure 00000055
и
Figure 00000056
.
16. Фармацевтически приемлемая соль, сольват или пролекарство соединения по любому одному из пп. 1-15.
17. Фармацевтическая композиция, содержащая соединение по любому одному из пп. 1-15, или фармацевтически приемлемую соль, сольват или пролекарство по п. 16, и фармацевтически приемлемый эксципиент.
18. Соединение по любому одному из пп. 1-15 или фармацевтически приемлемая соль, сольват или пролекарство по п. 16, или фармацевтическая композиция по п. 17 для применения в медицине.
19. Соединение, фармацевтически приемлемая соль, сольват, пролекарство или фармацевтическая композиция по п. 18 для применения в лечении или предотвращении заболевания, расстройства или патологического состояния, причем заболевание, расстройство или патологическое состояние отвечает на ингибирование NLRP3.
20. Соединение, фармацевтически приемлемая соль, сольват, пролекарство или фармацевтическая композиция по п. 18 или 19 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; а также
(xvi) аллодинии; а также
(xvii) любого заболевания, при котором у человека определено наличие зародышевой или соматической немолчащей мутации в NLRP3.
21. Соединение, фармацевтически приемлемая соль, сольват, пролекарство или фармацевтическая композиция по п. 18 или 19 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) многосистемного 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).
22. Способ ингибирования NLRP3, включающий применение соединения по любому одному из пп. 1-15 или фармацевтически приемлемой соли, сольвата или пролекарства по п. 16, или фармацевтической композиции по п. 17 для ингибирования NLRP3.
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