RU2020142104A - COMPOUNDS BASED ON ISOTHIAZOLO[5,4-d]PYRIMIDINE AS IRAK4 INHIBITOR - Google Patents

COMPOUNDS BASED ON ISOTHIAZOLO[5,4-d]PYRIMIDINE AS IRAK4 INHIBITOR Download PDF

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RU2020142104A
RU2020142104A RU2020142104A RU2020142104A RU2020142104A RU 2020142104 A RU2020142104 A RU 2020142104A RU 2020142104 A RU2020142104 A RU 2020142104A RU 2020142104 A RU2020142104 A RU 2020142104A RU 2020142104 A RU2020142104 A RU 2020142104A
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group
pharmaceutically acceptable
acceptable salt
alkyl
optical isomer
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RU2020142104A
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RU2801942C9 (en
RU2801942C2 (en
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Ян Чжан
Цзяньфэй ВАН
Хайчжун ТАНЬ
Цзе ЛИ
Цзянь Ли
Шухуэй Чэнь
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Чиа Тай Тяньцин Фармасьютикал Груп Ко., Лтд.
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1. Соединение формулы (II), его оптический изомер или фармацевтически приемлемая соль,1. The compound of formula (II), its optical isomer or pharmaceutically acceptable salt,
Figure 00000001
Figure 00000001
 где R1 выбран из группы, состоящей из CN, C1-6алкила и 3-6-членного гетероциклоалкила, где C1-6алкил и 3-6-членный гетероциклоалкил необязательно замещены 1, 2 или 3 Ra;where R1 is selected from the group consisting of CN, C1-6 alkyl and 3-6 membered heterocycloalkyl, where C1-6 alkyl and 3-6 membered heterocycloalkyl are optionally substituted with 1, 2 or 3 Ra; R2 выбран из группы, состоящей из C1-6алкила и 3-6-членного гетероциклоалкила, где C1-6алкил и 3-6-членный гетероциклоалкил необязательно замещены 1, 2 или 3 Rb;R2 is selected from the group consisting of C1-6 alkyl and 3-6 membered heterocycloalkyl, where C1-6 alkyl and 3-6 membered heterocycloalkyl are optionally substituted with 1, 2 or 3 Rb; R3 выбран из группы, состоящей из H, F, Cl, Br, I, OH, NH2, CN, C1-6алкила, -C(=O)-O-C1-6алкила, -C(=O)-C1-6алкила и C3-6циклоалкила, где C1-6алкил, -C(=O)-O-C1-6алкил, -C(=O)-C1-6алкил и C3-6циклоалкил необязательно замещены 1, 2 или 3 Rc;R3 is selected from the group consisting of H, F, Cl, Br, I, OH, NH2, CN, C1-6 alkyl, -C(=O)-O-C1-6 alkyl, -C(=O)-C1-6 alkyl and C3-6cycloalkyl, where C1-6alkyl, -C(=O)-O-C1-6alkyl, -C(=O)-C1-6alkyl and C3-6cycloalkyl are optionally substituted with 1, 2 or 3 Rc; кольцо A выбрано из группы, состоящей из 3-10-членного гетероциклоалкила, и 3-10-членный гетероциклоалкил необязательно замещен 1, 2 или 3 Rd;ring A is selected from the group consisting of 3-10 membered heterocycloalkyl and 3-10 membered heterocycloalkyl is optionally substituted with 1, 2 or 3 Rd; L1 выбран из группы, состоящей из O и N (R4);L1 is selected from the group consisting of O and N (R4); L2 выбран из группы, состоящей из одинарной связи, CH2 и CH2CH2;L2 is selected from the group consisting of a single bond, CH2 and CH2CH2; R4 выбран из группы, состоящей из H и Me;R4 is selected from the group consisting of H and Me; каждый Ra независимо выбран из группы, состоящей из F, Cl, Br, I, OH, NH2, CN и COOH;each Ra is independently selected from the group consisting of F, Cl, Br, I, OH, NH2, CN and COOH; каждый Rb независимо выбран из группы, состоящей из F, Cl, Br, I, OH, NH2, COOH и Me;each Rb is independently selected from the group consisting of F, Cl, Br, I, OH, NH2, COOH and Me; каждый Rc независимо выбран из группы, состоящей из F, Cl, Br, I, OH, NH2 и CN;each Rc is independently selected from the group consisting of F, Cl, Br, I, OH, NH2 and CN; каждый Rd независимо выбран из группы, состоящей из F, Cl, Br, I, OH, NH2 и CN;each Rd is independently selected from the group consisting of F, Cl, Br, I, OH, NH2 and CN; 3-6-членный гетероциклоалкил содержит 1, 2 или 3 гетероатома или гетероатомные группы, независимо выбранные из группы, состоящей из -O-, -S-, -NH- и N; и3-6 membered heterocycloalkyl contains 1, 2 or 3 heteroatoms or heteroatomic groups independently selected from the group consisting of -O-, -S-, -NH- and N; and 3-10-членный гетероциклоалкил содержит 1, 2 или 3 гетероатома или гетероатомные группы, независимо выбранные из группы, состоящей из -O-, -S-, -NH-, N и -C(=O)NH-.A 3-10 membered heterocycloalkyl contains 1, 2 or 3 heteroatoms or heteroatomic groups independently selected from the group consisting of -O-, -S-, -NH-, N and -C(=O)NH-. 2. Соединение формулы (III), его оптический изомер или фармацевтически приемлемая соль,2. The compound of formula (III), its optical isomer or pharmaceutically acceptable salt,
Figure 00000002
Figure 00000002
 где R1 выбран из группы, состоящей из CN, C1-6алкила и 3-6-членного гетероциклоалкила, где C1-6алкил и 3-6-членный гетероциклоалкил необязательно замещены 1, 2 или 3 Ra;where R1 is selected from the group consisting of CN, C1-6 alkyl and 3-6 membered heterocycloalkyl, where C1-6 alkyl and 3-6 membered heterocycloalkyl are optionally substituted with 1, 2 or 3 Ra; R2 выбран из группы, состоящей из C1-6алкила, C3-8циклоалкила и 3-6-членного гетероциклоалкила, где C1-6алкил, C3-8циклоалкил и 3-6-членный гетероциклоалкил необязательно замещены 1, 2 или 3 Rb;R2 is selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl and 3-6 membered heterocycloalkyl, where C1-6 alkyl, C3-8 cycloalkyl and 3-6 membered heterocycloalkyl are optionally substituted with 1, 2 or 3 Rb; R3 выбран из группы, состоящей из H, F, Cl, Br, I, OH, NH2, CN, COOH, C1-6алкила, C1-6алкиламино, -C(=O)-O-C1-6алкила, -C(=O)-C1-6алкила и C3-6циклоалкила, где C1-6алкил, C1-6алкиламино, -C(=O)-O-C1-6алкил, -C(=O)-C1-6алкил и C3-6циклоалкил необязательно замещены 1, 2 или 3 Rc;R3 is selected from the group consisting of H, F, Cl, Br, I, OH, NH2, CN, COOH, C1-6 alkyl, C1-6 alkylamino, -C(=O)-O-C1-6 alkyl, -C(= O)-C1-6alkyl and C3-6cycloalkyl, where C1-6alkyl, C1-6alkylamino, -C(=O)-O-C1-6alkyl, -C(=O)-C1-6alkyl and C3-6cycloalkyl are optionally substituted with 1 , 2 or 3 Rc; кольцо A выбрано из группы, состоящей из 3-10-членного гетероциклоалкила, и 3-10-членный гетероциклоалкил необязательно замещен 1, 2 или 3 Rd;ring A is selected from the group consisting of 3-10 membered heterocycloalkyl and 3-10 membered heterocycloalkyl is optionally substituted with 1, 2 or 3 Rd; L1 выбран из группы, состоящей из O и N (R4);L1 is selected from the group consisting of O and N (R4); L2 выбран из группы, состоящей из одинарной связи, CH2 и CH2CH2;L2 is selected from the group consisting of a single bond, CH2 and CH2CH2; R4 выбран из группы, состоящей из H и Me;R4 is selected from the group consisting of H and Me; каждый Ra независимо выбран из группы, состоящей из F, Cl, Br, I, OH, NH2, CN и COOH;each Ra is independently selected from the group consisting of F, Cl, Br, I, OH, NH2, CN and COOH; каждый Rb независимо выбран из группы, состоящей из F, Cl, Br, I, OH, NH2, COOH и Me;each Rb is independently selected from the group consisting of F, Cl, Br, I, OH, NH2, COOH and Me; каждый Rc независимо выбран из группы, состоящей из F, Cl, Br, I, OH, NH2 и CN;each Rc is independently selected from the group consisting of F, Cl, Br, I, OH, NH2 and CN; каждый Rd независимо выбран из группы, состоящей из H, F, Cl, Br, I, OH, NH2 и CN;each Rd is independently selected from the group consisting of H, F, Cl, Br, I, OH, NH2 and CN; 3-6-членный гетероциклоалкил содержит 1, 2 или 3 гетероатома или гетероатомные группы, независимо выбранные из группы, состоящей из -O-, -S-, -NH- и N; и3-6 membered heterocycloalkyl contains 1, 2 or 3 heteroatoms or heteroatomic groups independently selected from the group consisting of -O-, -S-, -NH- and N; and 3-10-членный гетероциклоалкил содержит 1, 2 или 3 гетероатома или гетероатомные группы, независимо выбранные из группы, состоящей из -O-, -S-, -NH-, N и -C(=O)NH-.A 3-10 membered heterocycloalkyl contains 1, 2 or 3 heteroatoms or heteroatomic groups independently selected from the group consisting of -O-, -S-, -NH-, N and -C(=O)NH-. 3. Соединение, его оптический изомер или фармацевтически приемлемая соль по любому из пп. 1-2, где R1 выбран из группы, состоящей из C1-3алкила и тетрагидропиранила, где C1-3алкил и тетрагидропиранил необязательно замещены 1, 2 или 3 Ra.3. Connection, its optical isomer or pharmaceutically acceptable salt according to any one of paragraphs. 1-2, where R1 is selected from the group consisting of C1-3 alkyl and tetrahydropyranyl, where C1-3 alkyl and tetrahydropyranyl are optionally substituted with 1, 2 or 3 Ra. 4. Соединение, его оптический изомер или фармацевтически приемлемая соль по п. 3, где R1 выбран из группы, состоящей из Me, Et,
Figure 00000003
и
Figure 00000004
, где Me, Et,
Figure 00000003
и
Figure 00000004
необязательно замещены 1, 2 или 3 Ra.4. The compound, its optical isomer or pharmaceutically acceptable salt according to claim 3, where R1 is selected from the group consisting of Me, Et,
Figure 00000003
and
Figure 00000004
, where Me, Et,
Figure 00000003
and
Figure 00000004
optionally substituted with 1, 2 or 3 Ra. 5. Соединение, его оптический изомер или фармацевтически приемлемая соль по п. 4, где R1 выбран из группы, состоящей из Me, Et,
Figure 00000003
,
Figure 00000004
,
Figure 00000005
и
Figure 00000006
.5. The compound, its optical isomer or pharmaceutically acceptable salt according to claim 4, where R1 is selected from the group consisting of Me, Et,
Figure 00000003
,
Figure 00000004
,
Figure 00000005
and
Figure 00000006
. 6. Соединение, его оптический изомер или фармацевтически приемлемая соль по любому из пп. 1-2, где R2 выбран из группы, состоящей из C1-3алкила, C4-6циклоалкила, тетрагидропиранила, оксетанила, тетрагидрофуранила и 1,4-диоксанила, где C1-3алкил, C4-6циклоалкил, тетрагидропиранил, оксетанил, тетрагидрофуранил и 1,4-диоксанил необязательно замещены 1, 2 или 3 Rb.6. Connection, its optical isomer or pharmaceutically acceptable salt according to any one of paragraphs. 1-2, where R2 is selected from the group consisting of C1-3 alkyl, C4-6 cycloalkyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl and 1,4-dioxanyl, where C1-3 alkyl, C4-6 cycloalkyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl and 1,4 -dioxanyl is optionally substituted with 1, 2 or 3 Rb. 7. Соединение, его оптический изомер или фармацевтически приемлемая соль по п. 6, где R2 выбран из группы, состоящей из Me, Et,
Figure 00000007
,
Figure 00000008
,
Figure 00000009
,
Figure 00000010
и циклогексила, где Me, Et,
Figure 00000011
,
Figure 00000008
,
Figure 00000012
,
Figure 00000004
и циклогексил необязательно замещены 1, 2 или 3 Rb.7. The compound, its optical isomer or pharmaceutically acceptable salt according to claim 6, where R2 is selected from the group consisting of Me, Et,
Figure 00000007
,
Figure 00000008
,
Figure 00000009
,
Figure 00000010
and cyclohexyl, where Me, Et,
Figure 00000011
,
Figure 00000008
,
Figure 00000012
,
Figure 00000004
and cyclohexyl are optionally substituted with 1, 2 or 3 Rb. 8. Соединение, его оптический изомер или фармацевтически приемлемая соль по п. 7, где R2 выбран из группы, состоящей из Me, -CH2OH, Et,
Figure 00000013
,
Figure 00000014
,
Figure 00000015
,
Figure 00000016
,
Figure 00000008
,
Figure 00000017
,
Figure 00000004
и
Figure 00000009
.8. The compound, its optical isomer or pharmaceutically acceptable salt according to claim 7, where R2 is selected from the group consisting of Me, -CH2OH, Et,
Figure 00000013
,
Figure 00000014
,
Figure 00000015
,
Figure 00000016
,
Figure 00000008
,
Figure 00000017
,
Figure 00000004
and
Figure 00000009
. 9. Соединение, его оптический изомер или фармацевтически приемлемая соль по пп. 1, 2 или 8, где структурная единица
Figure 00000018
выбрана из группы, состоящей из Me, Et,
Figure 00000013
,
Figure 00000014
,
Figure 00000019
,
Figure 00000015
,
Figure 00000008
,
Figure 00000016
,
Figure 00000020
,
Figure 00000021
и
Figure 00000004
.9. Connection, its optical isomer or pharmaceutically acceptable salt according to PP. 1, 2 or 8, where the structural unit
Figure 00000018
selected from the group consisting of Me, Et,
Figure 00000013
,
Figure 00000014
,
Figure 00000019
,
Figure 00000015
,
Figure 00000008
,
Figure 00000016
,
Figure 00000020
,
Figure 00000021
and
Figure 00000004
. 10. Соединение, его оптический изомер или фармацевтически приемлемая соль по любому из пп. 1-2, где R3 выбран из группы, состоящей из H, F, Cl, Br, I, OH, NH2, CN, COOH, C1-3алкила, -N(C1-3алкил)2, -C(=O)-O-C1-3алкила, -C(=O)-C1-3алкила и C3-6циклоалкила, где C1-3алкил, -N(C1-3алкил)2, -C(=O)-O-C1-3алкил, -C(=O)-C1-3алкил и C3-6циклоалкил необязательно замещены 1, 2 или 3 Rc.10. Connection, its optical isomer or pharmaceutically acceptable salt according to any one of paragraphs. 1-2, where R3 is selected from the group consisting of H, F, Cl, Br, I, OH, NH2, CN, COOH, C1-3alkyl, -N(C1-3alkyl)2, -C(=O)- O-C1-3alkyl, -C(=O)-C1-3alkyl and C3-6cycloalkyl, where C1-3alkyl, -N(C1-3alkyl)2, -C(=O)-O-C1-3alkyl, -C (=O)-C1-3alkyl and C3-6cycloalkyl are optionally substituted with 1, 2 or 3 Rc. 11. Соединение, его оптический изомер или фармацевтически приемлемая соль по п. 10, где R3 выбран из группы, состоящей из H, F, Cl, Br, I, OH, NH2, CN, COOH, Me, Et,
Figure 00000022
,
Figure 00000023
,
Figure 00000024
, -C(=O)-O-Me, -C(=O)-O-Et и -C(=O)-Me.11. The compound, its optical isomer or pharmaceutically acceptable salt according to claim 10, where R3 is selected from the group consisting of H, F, Cl, Br, I, OH, NH2, CN, COOH, Me, Et,
Figure 00000022
,
Figure 00000023
,
Figure 00000024
, -C(=O)-O-Me, -C(=O)-O-Et and -C(=O)-Me. 12. Соединение, его оптический изомер или фармацевтически приемлемая соль по любому из пп. 1-2, где кольцо A выбрано из группы, состоящей из морфолинила, пиперазинила, 3-морфолинонила, 2-пиперазинонила, гомопиперазинила, 4,7-диазаспиро[2,5]октила, 3,6-диазабицикло[3,1,1]гептила, 2-азациклогексанонила, 2,5-диазабицикло[2.2.1]гептила и азетидинила, где морфолинил, пиперазинил, 3-морфолинонил, 2-пиперазинонил, гомопиперазинил, 4,7-диазаспиро[2,5]октил, 3,6-диазабицикло[3,1,1]гептил, 2-азациклогексанонил, 2,5-диазабицикло[2.2.1]гептил и азетидинил необязательно замещены 1, 2 или 3 Rd.12. Connection, its optical isomer or pharmaceutically acceptable salt according to any one of paragraphs. 1-2, wherein Ring A is selected from the group consisting of morpholinyl, piperazinyl, 3-morpholinonyl, 2-piperazinonyl, homopiperazinyl, 4,7-diazaspiro[2,5]octyl, 3,6-diazabicyclo[3,1,1 ]heptyl, 2-azacyclohexanonyl, 2,5-diazabicyclo[2.2.1]heptyl and azetidinyl, where morpholinyl, piperazinyl, 3-morpholinonyl, 2-piperazinonyl, homopiperazinyl, 4,7-diazaspiro[2.5]octyl, 3, 6-diazabicyclo[3,1,1]heptyl, 2-azacyclohexanonyl, 2,5-diazabicyclo[2.2.1]heptyl and azetidinyl are optionally substituted with 1, 2 or 3 Rd. 13. Соединение, его оптический изомер или фармацевтически приемлемая соль по п. 12, где кольцо A выбрано из группы, состоящей из13. The compound, its optical isomer or pharmaceutically acceptable salt according to claim 12, where ring A is selected from the group consisting of
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
и
Figure 00000038
.
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
and
Figure 00000038
. 14. Соединение, его оптический изомер или фармацевтически приемлемая соль по п. 13, где структурная единица
Figure 00000039
выбрана из группы, состоящей из
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
,
Figure 00000056
,
Figure 00000057
,
Figure 00000058
,
Figure 00000059
,
Figure 00000060
,
Figure 00000061
,
Figure 00000062
,
Figure 00000063
,
Figure 00000064
,
Figure 00000065
,
Figure 00000066
,
Figure 00000067
,
Figure 00000068
и
Figure 00000069
.14. The compound, its optical isomer or pharmaceutically acceptable salt according to claim 13, where the structural unit
Figure 00000039
selected from the group consisting of
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
,
Figure 00000056
,
Figure 00000057
,
Figure 00000058
,
Figure 00000059
,
Figure 00000060
,
Figure 00000061
,
Figure 00000062
,
Figure 00000063
,
Figure 00000064
,
Figure 00000065
,
Figure 00000066
,
Figure 00000067
,
Figure 00000068
and
Figure 00000069
. 15. Соединение, его оптический изомер или фармацевтически приемлемая соль по любому из пп. 1-11, которые выбраны из:15. Connection, its optical isomer or pharmaceutically acceptable salt according to any one of paragraphs. 1-11, which are selected from:
Figure 00000070
Figure 00000071
Figure 00000072
Figure 00000073
Figure 00000074
Figure 00000075
Figure 00000076
Figure 00000077
Figure 00000078
Figure 00000079
Figure 00000080
Figure 00000081
Figure 00000082
Figure 00000070
Figure 00000071
Figure 00000072
Figure 00000073
Figure 00000074
Figure 00000075
Figure 00000076
Figure 00000077
Figure 00000078
Figure 00000079
Figure 00000080
Figure 00000081
Figure 00000082
 R1, R2, R3, L1 и L2 определены в любом из пп. 1-11.R1, R2, R3, L1 and L2 are defined in any one of paragraphs. 1-11. 16.Соединение следующей формулы, его оптический изомер или фармацевтически приемлемая соль, которые выбраны из: 16. A compound of the following formula, its optical isomer or pharmaceutically acceptable salt, which is selected from:
Figure 00000083
,
Figure 00000084
,
Figure 00000085
,
Figure 00000086
,
Figure 00000087
,
Figure 00000088
,
Figure 00000089
,
Figure 00000090
,
Figure 00000091
,
Figure 00000092
,
Figure 00000093
,
Figure 00000094
,
Figure 00000095
,
Figure 00000096
,
Figure 00000097
,
Figure 00000098
,
Figure 00000099
,
Figure 00000100
,
Figure 00000101
,
Figure 00000102
,
Figure 00000103
,
Figure 00000104
,
Figure 00000105
,
Figure 00000106
,
Figure 00000107
,
Figure 00000108
,
Figure 00000109
,
Figure 00000110
,
Figure 00000111
,
Figure 00000112
,
Figure 00000113
,
Figure 00000114
,
Figure 00000115
,
Figure 00000116
,
Figure 00000117
,
Figure 00000118
,
Figure 00000119
,
Figure 00000120
,
Figure 00000121
,
Figure 00000122
,
Figure 00000123
,
Figure 00000124
,
Figure 00000125
,
Figure 00000126
,
Figure 00000127
,
Figure 00000128
,
Figure 00000129
,
Figure 00000130
,
Figure 00000131
,
Figure 00000132
и
Figure 00000133
.
Figure 00000083
,
Figure 00000084
,
Figure 00000085
,
Figure 00000086
,
Figure 00000087
,
Figure 00000088
,
Figure 00000089
,
Figure 00000090
,
Figure 00000091
,
Figure 00000092
,
Figure 00000093
,
Figure 00000094
,
Figure 00000095
,
Figure 00000096
,
Figure 00000097
,
Figure 00000098
,
Figure 00000099
,
Figure 00000100
,
Figure 00000101
,
Figure 00000102
,
Figure 00000103
,
Figure 00000104
,
Figure 00000105
,
Figure 00000106
,
Figure 00000107
,
Figure 00000108
,
Figure 00000109
,
Figure 00000110
,
Figure 00000111
,
Figure 00000112
,
Figure 00000113
,
Figure 00000114
,
Figure 00000115
,
Figure 00000116
,
Figure 00000117
,
Figure 00000118
,
Figure 00000119
,
Figure 00000120
,
Figure 00000121
,
Figure 00000122
,
Figure 00000123
,
Figure 00000124
,
Figure 00000125
,
Figure 00000126
,
Figure 00000127
,
Figure 00000128
,
Figure 00000129
,
Figure 00000130
,
Figure 00000131
,
Figure 00000132
and
Figure 00000133
. 17. Соединение, его оптический изомер или фармацевтически приемлемая соль по п. 16, которые выбраны из:17. The compound, its optical isomer or pharmaceutically acceptable salt according to claim 16, which are selected from:
Figure 00000134
,
Figure 00000135
,
Figure 00000136
,
Figure 00000137
,
Figure 00000138
,
Figure 00000134
,
Figure 00000139
,
Figure 00000140
,
Figure 00000141
,
Figure 00000142
,
Figure 00000143
,
Figure 00000144
,
Figure 00000145
,
Figure 00000146
,
Figure 00000147
,
Figure 00000148
,
Figure 00000149
,
Figure 00000150
,
Figure 00000151
,
Figure 00000152
,
Figure 00000153
,
Figure 00000154
Figure 00000155
,
Figure 00000156
,
Figure 00000157
,
Figure 00000158
,
Figure 00000159
,
Figure 00000160
,
Figure 00000161
,
Figure 00000162
,
Figure 00000163
,
Figure 00000164
,
Figure 00000165
,
Figure 00000166
,
Figure 00000167
,
Figure 00000168
,
Figure 00000169
,
Figure 00000170
,
Figure 00000171
,
Figure 00000172
,
Figure 00000173
,
Figure 00000174
,
Figure 00000175
,
Figure 00000176
,
Figure 00000177
,
Figure 00000178
,
Figure 00000179
,
Figure 00000180
,
Figure 00000181
,
Figure 00000182
,
Figure 00000183
,
Figure 00000184
,
Figure 00000185
,
Figure 00000186
,
Figure 00000187
,
Figure 00000188
и
Figure 00000189
.
Figure 00000134
,
Figure 00000135
,
Figure 00000136
,
Figure 00000137
,
Figure 00000138
,
Figure 00000134
,
Figure 00000139
,
Figure 00000140
,
Figure 00000141
,
Figure 00000142
,
Figure 00000143
,
Figure 00000144
,
Figure 00000145
,
Figure 00000146
,
Figure 00000147
,
Figure 00000148
,
Figure 00000149
,
Figure 00000150
,
Figure 00000151
,
Figure 00000152
,
Figure 00000153
,
Figure 00000154
Figure 00000155
,
Figure 00000156
,
Figure 00000157
,
Figure 00000158
,
Figure 00000159
,
Figure 00000160
,
Figure 00000161
,
Figure 00000162
,
Figure 00000163
,
Figure 00000164
,
Figure 00000165
,
Figure 00000166
,
Figure 00000167
,
Figure 00000168
,
Figure 00000169
,
Figure 00000170
,
Figure 00000171
,
Figure 00000172
,
Figure 00000173
,
Figure 00000174
,
Figure 00000175
,
Figure 00000176
,
Figure 00000177
,
Figure 00000178
,
Figure 00000179
,
Figure 00000180
,
Figure 00000181
,
Figure 00000182
,
Figure 00000183
,
Figure 00000184
,
Figure 00000185
,
Figure 00000186
,
Figure 00000187
,
Figure 00000188
and
Figure 00000189
. 18. Фармацевтическая композиция, содержащая терапевтически эффективное количество соединения, его изомера или фармацевтически приемлемой соли по любому из пп. 1-17 в качестве активного ингредиента и фармацевтически приемлемый носитель.18. Pharmaceutical composition containing a therapeutically effective amount of a compound, its isomer or pharmaceutically acceptable salt according to any one of paragraphs. 1-17 as active ingredient and a pharmaceutically acceptable carrier. 19. Применение соединения, его изомера или его фармацевтически приемлемой соли по любому из пп. 1-17 для получения ингибитора IRAK4.19. The use of a compound, its isomer or its pharmaceutically acceptable salt according to any one of paragraphs. 1-17 to obtain an IRAK4 inhibitor. 20. Применение композиции по п. 18 для получения ингибитора IRAK4. 20. Use of a composition according to claim 18 for the preparation of an IRAK4 inhibitor.
RU2020142104A 2018-06-25 2019-06-25 COMPOUNDS BASED ON ISOTHIAZOLO[5,4-d]PYRIMIDINE AS IRAK4 INHIBITOR RU2801942C9 (en)

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CN201910463156.6 2019-05-30

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