RU2011116111A - Сульфонилсодержащие соединения, которые селективно модулируют рецептор св2 - Google Patents
Сульфонилсодержащие соединения, которые селективно модулируют рецептор св2 Download PDFInfo
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- RU2011116111A RU2011116111A RU2011116111/04A RU2011116111A RU2011116111A RU 2011116111 A RU2011116111 A RU 2011116111A RU 2011116111/04 A RU2011116111/04 A RU 2011116111/04A RU 2011116111 A RU2011116111 A RU 2011116111A RU 2011116111 A RU2011116111 A RU 2011116111A
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- Prior art keywords
- alkyl
- hydrogen
- cycloalkyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract 14
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical class O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 20
- 239000001257 hydrogen Substances 0.000 claims abstract 20
- 229910052736 halogen Inorganic materials 0.000 claims abstract 12
- 150000002367 halogens Chemical class 0.000 claims abstract 12
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 10
- -1 C1-C4-acyl Chemical group 0.000 claims abstract 9
- 125000001424 substituent group Chemical group 0.000 claims abstract 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 8
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims abstract 7
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 7
- 125000003118 aryl group Chemical group 0.000 claims abstract 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 6
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 3
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims abstract 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims abstract 2
- 125000002950 monocyclic group Chemical group 0.000 claims abstract 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 8
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 7
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 4
- 125000003386 piperidinyl group Chemical group 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 125000002393 azetidinyl group Chemical group 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 3
- 208000002193 Pain Diseases 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 125000004276 dioxalanyl group Chemical group 0.000 claims 2
- 125000000532 dioxanyl group Chemical group 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims 2
- 208000004998 Abdominal Pain Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 208000019838 Blood disease Diseases 0.000 claims 1
- 206010058019 Cancer Pain Diseases 0.000 claims 1
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 1
- 208000002881 Colic Diseases 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 208000009329 Graft vs Host Disease Diseases 0.000 claims 1
- 206010019233 Headaches Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 206010065390 Inflammatory pain Diseases 0.000 claims 1
- 208000019693 Lung disease Diseases 0.000 claims 1
- 208000023178 Musculoskeletal disease Diseases 0.000 claims 1
- 206010051606 Necrotising colitis Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 claims 1
- 208000001294 Nociceptive Pain Diseases 0.000 claims 1
- 206010037660 Pyrexia Diseases 0.000 claims 1
- 206010063837 Reperfusion injury Diseases 0.000 claims 1
- 208000025747 Rheumatic disease Diseases 0.000 claims 1
- 208000005392 Spasm Diseases 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 208000030961 allergic reaction Diseases 0.000 claims 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000030172 endocrine system disease Diseases 0.000 claims 1
- 208000030533 eye disease Diseases 0.000 claims 1
- 230000027950 fever generation Effects 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 1
- 208000007565 gingivitis Diseases 0.000 claims 1
- 208000024908 graft versus host disease Diseases 0.000 claims 1
- 210000003714 granulocyte Anatomy 0.000 claims 1
- 238000001631 haemodialysis Methods 0.000 claims 1
- 231100000869 headache Toxicity 0.000 claims 1
- 208000014951 hematologic disease Diseases 0.000 claims 1
- 208000018706 hematopoietic system disease Diseases 0.000 claims 1
- 230000000322 hemodialysis Effects 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 208000019423 liver disease Diseases 0.000 claims 1
- 208000017445 musculoskeletal system disease Diseases 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 208000004995 necrotizing enterocolitis Diseases 0.000 claims 1
- 208000004296 neuralgia Diseases 0.000 claims 1
- 230000000626 neurodegenerative effect Effects 0.000 claims 1
- 208000021722 neuropathic pain Diseases 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 230000008816 organ damage Effects 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 201000000306 sarcoidosis Diseases 0.000 claims 1
- 230000035939 shock Effects 0.000 claims 1
- 208000017520 skin disease Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 230000003685 thermal hair damage Effects 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
- 230000008733 trauma Effects 0.000 claims 1
- 210000004291 uterus Anatomy 0.000 claims 1
- 208000019553 vascular disease Diseases 0.000 claims 1
- 208000009935 visceral pain Diseases 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
- 0 CC(C)(COC(C(C)(C)S(CCCC(*)(*)*)(=O)=O)=O)c1n[o]c(NC(C)=O)c1 Chemical compound CC(C)(COC(C(C)(C)S(CCCC(*)(*)*)(=O)=O)=O)c1n[o]c(NC(C)=O)c1 0.000 description 4
- MQKSLQXGEPJSNF-UHFFFAOYSA-N CC(C(C)(C)c1cc(NC(C(C)(C)SCC2CCOCC2)=O)n[o]1)O Chemical compound CC(C(C)(C)c1cc(NC(C(C)(C)SCC2CCOCC2)=O)n[o]1)O MQKSLQXGEPJSNF-UHFFFAOYSA-N 0.000 description 1
- VYIFDHJKQMISLP-UHFFFAOYSA-N CC(C(C)(C)c1n[o]c(NC(C)=O)c1)O Chemical compound CC(C(C)(C)c1n[o]c(NC(C)=O)c1)O VYIFDHJKQMISLP-UHFFFAOYSA-N 0.000 description 1
- SFJQFVZDSPCNRI-UHFFFAOYSA-N CC(C)(C(Nc1cc(CCCCO)n[o]1)=O)S(C1CCOCC1)(=O)=O Chemical compound CC(C)(C(Nc1cc(CCCCO)n[o]1)=O)S(C1CCOCC1)(=O)=O SFJQFVZDSPCNRI-UHFFFAOYSA-N 0.000 description 1
- RZMKLFLXXZBKFM-UHFFFAOYSA-N CC(C)(C)Cc1nc(cc(cc2)S(C(C)(C)C(Nc3cc(C(C)(C)CO)n[o]3)=O)(=O)=O)c2[n]1CC1CC1 Chemical compound CC(C)(C)Cc1nc(cc(cc2)S(C(C)(C)C(Nc3cc(C(C)(C)CO)n[o]3)=O)(=O)=O)c2[n]1CC1CC1 RZMKLFLXXZBKFM-UHFFFAOYSA-N 0.000 description 1
- XJWCJJBZNUACLA-UHFFFAOYSA-N CC(C)(CO)c1n[o]c(NC(C)=O)c1 Chemical compound CC(C)(CO)c1n[o]c(NC(C)=O)c1 XJWCJJBZNUACLA-UHFFFAOYSA-N 0.000 description 1
- NTPWVCZBXWZNIJ-UHFFFAOYSA-N CC(C)(COC(C)=O)c1n[o]c(NC(C(C)(C)S(C2CCOCC2)(=O)=O)=O)c1 Chemical compound CC(C)(COC(C)=O)c1n[o]c(NC(C(C)(C)S(C2CCOCC2)(=O)=O)=O)c1 NTPWVCZBXWZNIJ-UHFFFAOYSA-N 0.000 description 1
- FVJUJAFOBDEYDE-UHFFFAOYSA-N CC(C)(COC(C)=O)c1n[o]c(NC(C(C)(C)SC2CCOCC2)=O)c1 Chemical compound CC(C)(COC(C)=O)c1n[o]c(NC(C(C)(C)SC2CCOCC2)=O)c1 FVJUJAFOBDEYDE-UHFFFAOYSA-N 0.000 description 1
- JRUWIZDZHRGRLW-UHFFFAOYSA-N CC(C)C(Nc1cc(C(C)(C)COC(C)=O)n[o]1)=O Chemical compound CC(C)C(Nc1cc(C(C)(C)COC(C)=O)n[o]1)=O JRUWIZDZHRGRLW-UHFFFAOYSA-N 0.000 description 1
- UIGQZFWDSKZUCL-UHFFFAOYSA-N CC1(c2n[o]c(NC(C)=O)c2)OCCC1 Chemical compound CC1(c2n[o]c(NC(C)=O)c2)OCCC1 UIGQZFWDSKZUCL-UHFFFAOYSA-N 0.000 description 1
- FFEDFQSEXJCCFG-UHFFFAOYSA-N CCCC(C)(C)c1n[o]c(NC(C(C)(C)SC2CCOCC2)=O)c1 Chemical compound CCCC(C)(C)c1n[o]c(NC(C(C)(C)SC2CCOCC2)=O)c1 FFEDFQSEXJCCFG-UHFFFAOYSA-N 0.000 description 1
- WHBKOWSSGOJYPP-UHFFFAOYSA-N CC[n]1nc(NC(C(C)(C)S(C2CCOCC2)(=O)=O)=O)nc1-c(cc1)ccc1OC Chemical compound CC[n]1nc(NC(C(C)(C)S(C2CCOCC2)(=O)=O)=O)nc1-c(cc1)ccc1OC WHBKOWSSGOJYPP-UHFFFAOYSA-N 0.000 description 1
- JMDMOXQXKMYZJX-PXYINDEMSA-N C[C@@H](C(C)(C)c1n[o]c(NC(C(C)(C)SCC2OCCOC2)=O)c1)O Chemical compound C[C@@H](C(C)(C)c1n[o]c(NC(C(C)(C)SCC2OCCOC2)=O)c1)O JMDMOXQXKMYZJX-PXYINDEMSA-N 0.000 description 1
- FICAQKBMCKEFDI-UHFFFAOYSA-N Cc1n[o]c(C)c1 Chemical compound Cc1n[o]c(C)c1 FICAQKBMCKEFDI-UHFFFAOYSA-N 0.000 description 1
- MPBPVACPFBSAFW-UHFFFAOYSA-N Cc1n[s]c(C)n1 Chemical compound Cc1n[s]c(C)n1 MPBPVACPFBSAFW-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
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Abstract
1. Соединение формулы (I) !! в которой: ! Het обозначает 5-членное гетероарильное кольцо, необязательно замещенное С1-С5-алкилом; ! R1 обозначает C1-С10-алкил, C1-C10-алкоксигруппу, С3-С10-циклоалкил, 3-10-членное насыщенное гетероциклическое кольцо, 5-10-членное моно- или бициклическое гетероарильное кольцо или фенил, каждый независимо необязательно содержащий 1-3 заместителя, выбранных из группы, включающей C1-C8-алкил, С1-С4-алкоксигруппу, С3-С10-циклоалкил, С3-С10-циклоалкил-С1-С5-алкил, С1-С4-алкилсульфонил, С1-С4-ацил, оксогруппу, цианогруппу, фенил, гидроксигруппу и галоген; ! R2 и R3 обозначают С1-С4-алкил или водород при условии, что оба R2 и R3 не могут обозначать водород; или R2 и R3 вместе с атомом углерода, к которому они присоединены, образуют 3-6-членное циклоалкильное или гетероциклическое кольцо; ! R4 обозначает водород или метил; !R5 выбран из ! , , , , , , , , , , , и ! или R5 обозначает 3-10-членное насыщенное гетероциклическое кольцо, необязательно замещенное 1-3 C1-C4-алкилами; ! m равно 0, 1, 2 или 3; ! каждый R6 независимо обозначает водород, C1-С6-алкил, 3-10-членное насыщенное гетероциклическое кольцо, арил, бензил или -(CH2)1-3-O-(CH2)0-1-X, где X обозначает арил или СН3, каждое гетероциклическое, бензильное или арильное кольцо необязательно замещено одним или более С1-С4-алкилом, C1-С4-алкоксигруппой или галогеном; !где R7 и R8 каждый независимо обозначает водород или С1-С4-алкил при условии, что оба R7 и R8 не могут обозначать водород, и где R7 и R8 необязательно могут циклизоваться с образованием С3-С7-циклоалкильного кольца; ! R9 обозначает С1-С4-алкил, который заменяет метиленовый атом водорода в -(СН2)n- или отсутствует; ! n равно 0, 1 или 2; ! где любой атом углерода в формуле (I) или л�
Claims (12)
1. Соединение формулы (I)
в которой:
Het обозначает 5-членное гетероарильное кольцо, необязательно замещенное С1-С5-алкилом;
R1 обозначает C1-С10-алкил, C1-C10-алкоксигруппу, С3-С10-циклоалкил, 3-10-членное насыщенное гетероциклическое кольцо, 5-10-членное моно- или бициклическое гетероарильное кольцо или фенил, каждый независимо необязательно содержащий 1-3 заместителя, выбранных из группы, включающей C1-C8-алкил, С1-С4-алкоксигруппу, С3-С10-циклоалкил, С3-С10-циклоалкил-С1-С5-алкил, С1-С4-алкилсульфонил, С1-С4-ацил, оксогруппу, цианогруппу, фенил, гидроксигруппу и галоген;
R2 и R3 обозначают С1-С4-алкил или водород при условии, что оба R2 и R3 не могут обозначать водород; или R2 и R3 вместе с атомом углерода, к которому они присоединены, образуют 3-6-членное циклоалкильное или гетероциклическое кольцо;
R4 обозначает водород или метил;
R5 выбран из
или R5 обозначает 3-10-членное насыщенное гетероциклическое кольцо, необязательно замещенное 1-3 C1-C4-алкилами;
m равно 0, 1, 2 или 3;
каждый R6 независимо обозначает водород, C1-С6-алкил, 3-10-членное насыщенное гетероциклическое кольцо, арил, бензил или -(CH2)1-3-O-(CH2)0-1-X, где X обозначает арил или СН3, каждое гетероциклическое, бензильное или арильное кольцо необязательно замещено одним или более С1-С4-алкилом, C1-С4-алкоксигруппой или галогеном;
где R7 и R8 каждый независимо обозначает водород или С1-С4-алкил при условии, что оба R7 и R8 не могут обозначать водород, и где R7 и R8 необязательно могут циклизоваться с образованием С3-С7-циклоалкильного кольца;
R9 обозначает С1-С4-алкил, который заменяет метиленовый атом водорода в -(СН2)n- или отсутствует;
n равно 0, 1 или 2;
где любой атом углерода в формуле (I) или любой указанный выше заместитель R, если это возможно, необязательно частично или полностью галогенирован;
или его фармацевтически приемлемая соль.
2. Соединение по п.1 и в котором
Het обозначает
R1 обозначает C1-С6-алкил, фенил, циклопропил, циклобутил, циклопентил, циклогексил, циклогептил, циклооктил, тетрагидрофуранил, тетрагидропиранил, азетидинил, пиперидинил; бензоксазолил, бензотиазолил, бензимидазолил, диоксаланил, диоксанил, оксазолил, изоксазолил, тиазолил, пиразолил, пирролил, имидазолил, тиенил, тиоморфолинил, 1,1-диоксо-1λ6-тиоморфолинил, морфолинил, пиридинил, пиримидинил, пиридазинил, пиразинил, триазинил, пирролидинил, пиперазинил, пуринил, хинолинил, дигидро-2Н-хинолинил, изохинолинил, хиназолинил, индазолил, индолил, бензофуранил, бензопиранил или бензодиоксолил, каждый необязательно содержащий 1-2 заместителя, выбранных из группы, включающей галоген, C1-С6-алкил, гидроксигруппу, C1-С4-алкоксигруппу, С1-С4-алкилсульфонил, С3-С10-циклоалкил-С1-С5-алкил или эксогруппу;
R2 и R3 независимо обозначают метил, этил, н-пропил, изопропил или водород при условии, что оба R2 и R3 не могут обозначать водород; или R2 и R3 вместе с атомом углерода, к которому они присоединены, образуют циклопропильное, циклобутильное или циклопентильное кольцо;
R5 выбран из
где Ar обозначает тетрагидропиранил или тетрагидрофуранил, каждый необязательно замещенный C1-С3-алкилом,
где R10 обозначает водород или метил, или R5 обозначает тетрагидропиранил или тетрагидрофуранил, каждый необязательно замещенный C1-С3-алкилом;
R6 обозначает водород, бензил, фенил или C1-С4-алкил, каждое бензильное или фенильное кольцо необязательно замещено одним или более C1-С4-алкилом, C1-С4-алкоксигруппой или галогеном;
R7 и R8 каждый обозначает C1-С3-алкил или C3-С6-циклоалкил, где R7 и R8 необязательно могут циклизоваться с образованием C3-С6-циклоалкильного кольца.
3. Соединение по п.2 и в котором
R1 обозначает C1-С5-алкил, фенил, циклопропил, циклобутил, циклопентил, циклогексил, циклогептил, тетрагидрофуранил, тетрагидропиранил, диоксаланил, диоксанил, азетидинил, пиперидинил, бензимидазолил, пирролил, пиридинил, пиримидинил, пиридазинил, пиразинил, пирролидинил или пиперазинил, каждый необязательно содержащий 1-2 заместителя, выбранных из группы, включающей галоген, C1-С6-алкил, C1-С4-алкилсульфонил, C3-С10-циклоалкил-C1-С5-алкил, гидроксигруппу, C1-С4-алкоксигруппу и оксогруппу;
R2 и R3 независимо обозначают метил, этил, н-пропил, изопропил или водород при условии, что оба R2 и R3 не могут обозначать водород; или R2 и R3 вместе с атомом углерода, к которому они присоединены, образуют циклопропильное, циклобутильное или циклопентильное кольцо;
n равно 0 или 1;
R5 выбран из
где Ar обозначает тетрагидропиранил или тетрагидрофуранил, каждый необязательно замещенный C1-С3-алкилом,
где R10 обозначает водород или метил, или R5 обозначает тетрагидропиранил или тетрагидрофуранил, каждый необязательно замещенный C1-С3-алкилом;
R6 обозначает водород, бензил, фенил или C1-С4-алкил, каждое бензильное или фенильное кольцо необязательно замещено одним или более C1-С4-алкилом, C1-С4-алкоксигруппой или галогеном;
R7 и R8 все обозначают C1-С3-алкил или C3-С6-циклоалкил, где R7 и R8 необязательно могут циклизоваться с образованием C3-С6-циклоалкильного кольца.
4. Соединение по п.3 и в котором
Het обозначает
R1 обозначает фенил или бензимидазолил, каждый необязательно содержащий 1-2 заместителя, выбранных из группы, включающей галоген, С1-С6-алкил, C1-С4-алкилсульфонил, C3-С6-циклоалкил-C1-С3-алкил, или оксогруппу;
или R1 обозначает C1-С5-алкил, циклопропил, циклобутил, циклопентил, циклогексил, тетрагидропиранил, тетрагидрофуранил, азетидинил, пирролидинил или пиперидинил, каждый необязательно содержащий заместитель, выбранный из группы, включающей галоген, C1-С4-алкил, C1-С4-алкоксигруппу, C1-С4-алкилсульфонил или оксогруппу;
R2 и R3 независимо обозначают метил или R2 и R3 вместе с атомом углерода, к которому они присоединены, образуют циклопропильное или циклобутильное кольцо;
R7 и R8 каждый обозначает C1-С2-алкил, где R7 и R8 необязательно могут циклизоваться с образованием C3-С6-циклоалкильного кольца.
6. Соединение по п.5 и в котором
R1 обозначает фенил или бензимидазолил, каждый необязательно содержащий 1-2 заместителя, выбранных из группы, включающей галоген, C1-С6-алкил или C3-С5-циклоалкил-C1-С3-алкил;
или R1 обозначает C1-С5-алкил, циклопропил, циклобутил, циклопентил, циклогексил, тетрагидропиранил, тетрагидрофуранил или пиперидинил, каждый необязательно содержащий заместитель, выбранный из группы, включающей галоген, C1-С4-алкил, C1-С4-алкоксигруппу или C1-С4-алкилсульфонил.
7. Соединение формулы (II)
в котором
формулы (I) выбран из столбца А1-А11 таблицы I и
формулы (I) выбран из столбца В1-В36 таблицы I,
или его фармацевтически приемлемая соль.
10. Фармацевтическая композиция, содержащая соединение по любому из пп.1-9 в терапевтически эффективном количестве и один или большее количество фармацевтически приемлемых носителей и/или вспомогательных веществ.
11. Способ лечения боли, включающий введение соединения по любому из пп.1-10 в терапевтически эффективном количестве.
12. Способ лечения заболевания или патологического состояния, выбранного из группы, включающей заболевание легких, ревматическое заболевание, аутоиммунное заболевание, скелетно-мышечное заболевание, аллергическое заболевание, аллергическую реакцию, сосудистое заболевание, кожное заболевание, заболевание почек, заболевание печени, желудочно-кишечное заболевание, нейродегенеративное заболевание глаз, заболевания уха, носа и горла, неврологическое заболевание, заболевание крови, опухоли, эндокринные заболевания, заболевания, связанные с трансплантацией органов и тканей и заболевания "трансплантат против хозяина", состояния тяжелого шока, острую боль, висцеральную боль, спазм желудочно-кишечного тракта или матки, колики, невропатическую боль, воспалительную и ноцицептивную боль, боль при раке, головную боль, рестеноз, атеросклероз, реперфузионное поражение, застойную сердечную недостаточность, инфаркт миокарда, термическое повреждение, множественное поражение органов после травмы, некротизирующий энтероколит и синдромы, связанные с гемодиализом, лейкофорезом и трансфузией гранулоцитов, саркоидоз, гингивит и гипертермию, включающий введение соединения по любому из пп.1-10 в терапевтически эффективном количестве.
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