CA2867175A1 - Phenyl-urea and phenyl-carbamate derivatives as inhibitors of protein aggregation - Google Patents
Phenyl-urea and phenyl-carbamate derivatives as inhibitors of protein aggregation Download PDFInfo
- Publication number
- CA2867175A1 CA2867175A1 CA2867175A CA2867175A CA2867175A1 CA 2867175 A1 CA2867175 A1 CA 2867175A1 CA 2867175 A CA2867175 A CA 2867175A CA 2867175 A CA2867175 A CA 2867175A CA 2867175 A1 CA2867175 A1 CA 2867175A1
- Authority
- CA
- Canada
- Prior art keywords
- ethyl
- methyl
- urea
- indol
- methylpiperazin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 230000004845 protein aggregation Effects 0.000 title claims abstract description 19
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 title abstract description 10
- PWXJULSLLONQHY-UHFFFAOYSA-N phenylcarbamic acid Chemical class OC(=O)NC1=CC=CC=C1 PWXJULSLLONQHY-UHFFFAOYSA-N 0.000 title abstract description 4
- 239000003112 inhibitor Substances 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 15
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 12
- 201000002832 Lewy body dementia Diseases 0.000 claims abstract description 10
- 208000001089 Multiple system atrophy Diseases 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 111
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 47
- 238000011282 treatment Methods 0.000 claims description 41
- -1 1H-benzimidazolyl Chemical group 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000006413 ring segment Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 3
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 3
- UFTHVNAXTAFSEM-UHFFFAOYSA-N SC(=O)NCCC1=CC=CN1 Chemical compound SC(=O)NCCC1=CC=CN1 UFTHVNAXTAFSEM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000003725 azepanyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- RBYNETHHEMQMNK-UHFFFAOYSA-N 1-(2-aminoethyl)-3-[3-ethyl-4-(1h-indol-3-ylmethyl)phenyl]urea Chemical compound CCC1=CC(NC(=O)NCCN)=CC=C1CC1=CNC2=CC=CC=C12 RBYNETHHEMQMNK-UHFFFAOYSA-N 0.000 claims 1
- GNCGFNQCHRFLBU-UHFFFAOYSA-N 1-(3-amino-3-iminopropyl)-3-[3-ethyl-4-(1h-indol-3-ylmethyl)phenyl]urea Chemical compound CCC1=CC(NC(=O)NCCC(N)=N)=CC=C1CC1=CNC2=CC=CC=C12 GNCGFNQCHRFLBU-UHFFFAOYSA-N 0.000 claims 1
- YKQHEDNVQMHJLH-UHFFFAOYSA-N 1-[3-(1h-indol-2-ylmethoxy)-5-propoxyphenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]thiourea Chemical compound C=1C(OCC=2NC3=CC=CC=C3C=2)=CC(OCCC)=CC=1NC(=S)NCCN1CCN(C)CC1 YKQHEDNVQMHJLH-UHFFFAOYSA-N 0.000 claims 1
- QYOKBBSVTMCTLM-UHFFFAOYSA-N 1-[3-(1h-indol-2-ylmethoxy)-5-propoxyphenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(OCC=2NC3=CC=CC=C3C=2)=CC(OCCC)=CC=1NC(=O)NCCN1CCN(C)CC1 QYOKBBSVTMCTLM-UHFFFAOYSA-N 0.000 claims 1
- WDNBIPQDFNRSFG-UHFFFAOYSA-N 1-[3-(1h-indol-3-ylmethoxy)-5-propoxyphenyl]-3-(2-piperazin-1-ylethyl)urea Chemical compound C=1C(OCC=2C3=CC=CC=C3NC=2)=CC(OCCC)=CC=1NC(=O)NCCN1CCNCC1 WDNBIPQDFNRSFG-UHFFFAOYSA-N 0.000 claims 1
- HOGDGYRAWLHIGX-UHFFFAOYSA-N 1-[3-(1h-indol-3-ylmethoxy)-5-propoxyphenyl]-3-(2-piperidin-4-ylethyl)urea Chemical compound C=1C(OCC=2C3=CC=CC=C3NC=2)=CC(OCCC)=CC=1NC(=O)NCCC1CCNCC1 HOGDGYRAWLHIGX-UHFFFAOYSA-N 0.000 claims 1
- CVGWWSWCDADCHQ-UHFFFAOYSA-N 1-[3-(1h-indol-3-ylmethyl)-5-methoxyphenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(OC)=CC(CC=2C3=CC=CC=C3NC=2)=CC=1NC(=O)NCCN1CCN(C)CC1 CVGWWSWCDADCHQ-UHFFFAOYSA-N 0.000 claims 1
- NXJSXLOWXWJKAV-UHFFFAOYSA-N 1-[3-(1h-indol-3-ylmethyl)-5-propan-2-yloxyphenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(OC(C)C)=CC(CC=2C3=CC=CC=C3NC=2)=CC=1NC(=O)NCCN1CCN(C)CC1 NXJSXLOWXWJKAV-UHFFFAOYSA-N 0.000 claims 1
- OEWMTCRSEPVHFY-UHFFFAOYSA-N 1-[3-[2-(1h-indol-3-yl)ethyl]-5-propan-2-ylphenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]thiourea Chemical compound C=1C(C(C)C)=CC(CCC=2C3=CC=CC=C3NC=2)=CC=1NC(=S)NCCN1CCN(C)CC1 OEWMTCRSEPVHFY-UHFFFAOYSA-N 0.000 claims 1
- QVPSBZWFQYGAKC-UHFFFAOYSA-N 1-[3-butyl-4-(1h-indol-3-ylmethyl)-5-(trifluoromethoxy)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(OC(F)(F)F)=C(CC=2C3=CC=CC=C3NC=2)C(CCCC)=CC=1NC(=O)NCCN1CCN(C)CC1 QVPSBZWFQYGAKC-UHFFFAOYSA-N 0.000 claims 1
- GGBQZKQFGCFYRL-UHFFFAOYSA-N 1-[3-butyl-4-(1h-indol-3-ylmethyl)-5-methoxyphenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(OC)=C(CC=2C3=CC=CC=C3NC=2)C(CCCC)=CC=1NC(=O)NCCN1CCN(C)CC1 GGBQZKQFGCFYRL-UHFFFAOYSA-N 0.000 claims 1
- VAGAPCWJTBONAS-UHFFFAOYSA-N 1-[3-butyl-5-(1h-imidazo[4,5-b]pyrazin-2-ylmethyl)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(CCCC)=CC(CC=2NC3=NC=CN=C3N=2)=CC=1NC(=O)NCCN1CCN(C)CC1 VAGAPCWJTBONAS-UHFFFAOYSA-N 0.000 claims 1
- DRKVIPKWAHSPMY-UHFFFAOYSA-N 1-[3-butyl-5-(1h-indol-3-ylmethoxy)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(OCC=2C3=CC=CC=C3NC=2)=CC(CCCC)=CC=1NC(=O)NCCN1CCN(C)CC1 DRKVIPKWAHSPMY-UHFFFAOYSA-N 0.000 claims 1
- QAKMKLOSXMOKPU-UHFFFAOYSA-N 1-[3-butyl-5-(1h-indol-3-ylmethyl)phenyl]-3-(2-piperidin-4-ylethyl)urea Chemical compound C=1C(CCCC)=CC(CC=2C3=CC=CC=C3NC=2)=CC=1NC(=O)NCCC1CCNCC1 QAKMKLOSXMOKPU-UHFFFAOYSA-N 0.000 claims 1
- DSDXCHSRGHORBB-UHFFFAOYSA-N 1-[3-butyl-5-(2,3-dihydro-1h-benzimidazol-2-ylmethyl)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(CCCC)=CC(CC2NC3=CC=CC=C3N2)=CC=1NC(=O)NCCN1CCN(C)CC1 DSDXCHSRGHORBB-UHFFFAOYSA-N 0.000 claims 1
- UDVLSYLVSYNMHJ-UHFFFAOYSA-N 1-[3-butyl-5-hydroxy-4-(1h-indol-3-ylmethyl)phenyl]-3-[2-(4,4-dimethylpiperazin-4-ium-1-yl)ethyl]urea;iodide Chemical compound [I-].C=1C(O)=C(CC=2C3=CC=CC=C3NC=2)C(CCCC)=CC=1NC(=O)NCCN1CC[N+](C)(C)CC1 UDVLSYLVSYNMHJ-UHFFFAOYSA-N 0.000 claims 1
- BUMROPPMYBHLLF-UHFFFAOYSA-N 1-[3-butyl-5-hydroxy-4-(1h-indol-3-ylmethyl)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C(O)=C(CC=2C3=CC=CC=C3NC=2)C(CCCC)=CC=1NC(=O)NCCN1CCN(C)CC1 BUMROPPMYBHLLF-UHFFFAOYSA-N 0.000 claims 1
- ZHPUPZFRXZBEKU-UHFFFAOYSA-N 1-[3-cyclohexyloxy-5-(1h-indol-3-ylmethyl)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C1CN(C)CCN1CCNC(=O)NC1=CC(CC=2C3=CC=CC=C3NC=2)=CC(OC2CCCCC2)=C1 ZHPUPZFRXZBEKU-UHFFFAOYSA-N 0.000 claims 1
- RDXTURUZNDFRCO-UHFFFAOYSA-N 1-[3-cyclopentyloxy-5-(1h-indol-3-ylmethyl)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C1CN(C)CCN1CCNC(=O)NC1=CC(CC=2C3=CC=CC=C3NC=2)=CC(OC2CCCC2)=C1 RDXTURUZNDFRCO-UHFFFAOYSA-N 0.000 claims 1
- LWYSHXBDBGXEDU-UHFFFAOYSA-N 1-[3-cyclopropyloxy-5-(1h-indol-3-ylmethyl)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C1CN(C)CCN1CCNC(=O)NC1=CC(CC=2C3=CC=CC=C3NC=2)=CC(OC2CC2)=C1 LWYSHXBDBGXEDU-UHFFFAOYSA-N 0.000 claims 1
- SRSIGTFBRAKBIH-UHFFFAOYSA-N 1-[3-ethyl-4-(1h-indol-3-ylmethyl)phenyl]-3-(2-piperazin-1-ylethyl)urea Chemical compound C=1C=C(CC=2C3=CC=CC=C3NC=2)C(CC)=CC=1NC(=O)NCCN1CCNCC1 SRSIGTFBRAKBIH-UHFFFAOYSA-N 0.000 claims 1
- DLRKIDHQJPSZET-UHFFFAOYSA-N 1-[3-ethyl-4-(1h-indol-3-ylmethyl)phenyl]-3-[2-(1h-imidazol-5-yl)ethyl]urea Chemical compound C=1C=C(CC=2C3=CC=CC=C3NC=2)C(CC)=CC=1NC(=O)NCCC1=CN=CN1 DLRKIDHQJPSZET-UHFFFAOYSA-N 0.000 claims 1
- FKFSPCZNABVGFH-UHFFFAOYSA-N 1-[3-ethyl-4-(1h-indol-3-ylmethyl)phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C=1C=C(CC=2C3=CC=CC=C3NC=2)C(CC)=CC=1NC(=O)NCCN1CCN(C)CC1 FKFSPCZNABVGFH-UHFFFAOYSA-N 0.000 claims 1
- PQGAEDFEJRCXRP-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)ethyl n-[3-(1h-indol-2-ylmethoxy)-5-propoxyphenyl]carbamate Chemical compound C=1C(OCC=2NC3=CC=CC=C3C=2)=CC(OCCC)=CC=1NC(=O)OCCN1CCN(C)CC1 PQGAEDFEJRCXRP-UHFFFAOYSA-N 0.000 claims 1
- BDGSCPUIKRRPFO-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)ethyl n-[3-[2-(1h-indol-3-yl)ethyl]-5-propan-2-ylphenyl]carbamate Chemical compound C=1C(C(C)C)=CC(CCC=2C3=CC=CC=C3NC=2)=CC=1NC(=O)OCCN1CCN(C)CC1 BDGSCPUIKRRPFO-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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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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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/14—Radicals substituted by nitrogen atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Organic Chemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| PCT/US2013/032552 WO2013148365A1 (en) | 2012-03-28 | 2013-03-15 | Phenyl-urea and phenyl-carbamate derivatives as inhibitors of protein aggregation |
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| CA2867175A1 true CA2867175A1 (en) | 2013-10-03 |
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| EA032374B1 (ru) | 2014-01-29 | 2019-05-31 | ЮСиБи БАЙОФАРМА СПРЛ | Гетероарильные амиды в качестве ингибиторов агрегации белков |
| WO2016040780A1 (en) * | 2014-09-11 | 2016-03-17 | Neuropore Therapies, Inc. | Aminomethyl- and methyloxy-linked tricyclic compounds as inhibitors of protein aggregation |
| US10975066B2 (en) | 2015-07-29 | 2021-04-13 | UCB Biopharma SRL | Bis-heteroaryl derivatives as modulators of protein aggregation |
| CN110191885B (zh) | 2017-01-26 | 2023-05-16 | Ucb生物制药私人有限公司 | 作为蛋白质聚集调节剂的烷氧基双-杂芳基衍生物 |
| RU2019126170A (ru) | 2017-01-26 | 2021-02-26 | Юсб Байофарма Спрл | Бисгетероарильные производные в качестве модуляторов агрегации белков |
| US10889584B2 (en) | 2017-01-26 | 2021-01-12 | UCB Biopharma SRL | Bicyclic bis-heteroaryl derivatives as modulators of protein aggregation |
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| EP0882048B1 (de) | 1996-01-26 | 2005-05-04 | ALTANA Pharma AG | 3-alkylimidazopyridine |
| US6617351B1 (en) | 1998-07-31 | 2003-09-09 | Eli Lilly And Company | Amide, carbamate, and urea derivatives |
| ES2292488T3 (es) | 1999-11-16 | 2008-03-16 | Boehringer Ingelheim Pharmaceuticals Inc. | Derivados de la urea, como agentes antiinflamatorios. |
| HU228960B1 (hu) * | 2000-10-30 | 2013-07-29 | Kudos Pharm Ltd | Ftalazinon-származékok |
| EP1402888A1 (en) | 2002-09-18 | 2004-03-31 | Jerini AG | The use of substituted carbocyclic compounds as rotamases inhibitors |
| WO2004080950A1 (en) | 2003-03-14 | 2004-09-23 | H. Lundbeck A/S | Substituted aniline derivatives |
| US7906537B2 (en) * | 2003-03-21 | 2011-03-15 | H. Lundbeck A/S | Substituted p-diaminobenzene derivatives |
| WO2005048953A2 (en) * | 2003-11-13 | 2005-06-02 | Ambit Biosciences Corporation | Amide derivatives as kinase modulators |
| MY153898A (en) * | 2005-06-22 | 2015-04-15 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| CA2650007A1 (en) | 2006-04-21 | 2007-11-01 | Smithkline Beecham Corporation | Il-8 receptor antagonists |
| WO2008044688A1 (en) * | 2006-10-11 | 2008-04-17 | Daiichi Sankyo Company, Limited | Urea derivative |
| WO2010036316A1 (en) | 2008-09-24 | 2010-04-01 | Yangbo Feng | Urea and carbamate compounds and analogs as kinase inhibitors |
| RU2012129882A (ru) * | 2009-12-16 | 2014-01-27 | Нейропор Терапиз, Инк. | Соединение |
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| EP2830608B8 (en) | 2020-01-15 |
| NZ631388A (en) | 2016-01-29 |
| KR20150002713A (ko) | 2015-01-07 |
| US20150166543A1 (en) | 2015-06-18 |
| ES2768602T3 (es) | 2020-06-23 |
| US9527852B2 (en) | 2016-12-27 |
| HK1202452A1 (en) | 2015-10-02 |
| EP2830608A1 (en) | 2015-02-04 |
| IL234825A0 (en) | 2014-12-31 |
| JP6159388B2 (ja) | 2017-07-05 |
| RU2014143242A (ru) | 2016-05-20 |
| MX2014011615A (es) | 2015-01-19 |
| WO2013148365A1 (en) | 2013-10-03 |
| CN104363903A (zh) | 2015-02-18 |
| IN2014DN08633A (enExample) | 2015-05-22 |
| EP2830608B1 (en) | 2019-12-11 |
| AU2013240219A1 (en) | 2014-10-09 |
| EP2830608A4 (en) | 2015-08-19 |
| JP2015515465A (ja) | 2015-05-28 |
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