UA79309C2 - Heterocyclic compounds - Google Patents
Heterocyclic compounds Download PDFInfo
- Publication number
- UA79309C2 UA79309C2 UAA200503209A UA2005003209A UA79309C2 UA 79309 C2 UA79309 C2 UA 79309C2 UA A200503209 A UAA200503209 A UA A200503209A UA 2005003209 A UA2005003209 A UA 2005003209A UA 79309 C2 UA79309 C2 UA 79309C2
- Authority
- UA
- Ukraine
- Prior art keywords
- methanone
- alkyl
- benzoimidazol
- methylpiperazin
- methyl
- Prior art date
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 111
- 125000001424 substituent group Chemical group 0.000 claims abstract description 19
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 5
- 230000000172 allergic effect Effects 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 3
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- -1 hydroxy, amino Chemical group 0.000 claims description 51
- 229910052799 carbon Inorganic materials 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 229910052796 boron Inorganic materials 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 8
- 201000010105 allergic rhinitis Diseases 0.000 claims description 8
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 8
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 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 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- RHXSYTACTOMVLJ-UHFFFAOYSA-N 1H-benzimidazole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=NC2=C1 RHXSYTACTOMVLJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- GKSPBWMLZIYREQ-UHFFFAOYSA-N (4-chloro-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=C(Cl)C=CC=C2N1 GKSPBWMLZIYREQ-UHFFFAOYSA-N 0.000 claims description 3
- JQTLCZZJXYVAEB-UHFFFAOYSA-N (4-methyl-1h-benzimidazol-2-yl)-(3-methylpiperazin-1-yl)methanone Chemical compound C1CNC(C)CN1C(=O)C1=NC2=C(C)C=CC=C2N1 JQTLCZZJXYVAEB-UHFFFAOYSA-N 0.000 claims description 3
- KCJHNHGIQWVNSS-UHFFFAOYSA-N (4-methyl-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=C(C)C=CC=C2N1 KCJHNHGIQWVNSS-UHFFFAOYSA-N 0.000 claims description 3
- RURXHJWOGXWBLU-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(C(F)(F)F)=CC=C2N1 RURXHJWOGXWBLU-UHFFFAOYSA-N 0.000 claims description 3
- IRGAQXDRTLJBQB-UHFFFAOYSA-N (5,6-difluoro-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(F)=C(F)C=C2N1 IRGAQXDRTLJBQB-UHFFFAOYSA-N 0.000 claims description 3
- ZCDFRCAJGXZHBJ-UHFFFAOYSA-N 6-methyl-1h-benzimidazole-2-carboxylic acid Chemical compound CC1=CC=C2N=C(C(O)=O)NC2=C1 ZCDFRCAJGXZHBJ-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- PSKWCTYZMXFVDK-UHFFFAOYSA-N [2-(4-methylpiperazine-1-carbonyl)-3h-benzimidazol-5-yl]-phenylmethanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(C(=O)C=3C=CC=CC=3)=CC=C2N1 PSKWCTYZMXFVDK-UHFFFAOYSA-N 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- KVHNNAFIEYQJFP-UHFFFAOYSA-N (4-amino-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=C(N)C=CC=C2N1 KVHNNAFIEYQJFP-UHFFFAOYSA-N 0.000 claims description 2
- OYCPMRKNILHXGZ-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-(4-methyl-1h-benzimidazol-2-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=NC2=C(C)C=CC=C2N1 OYCPMRKNILHXGZ-UHFFFAOYSA-N 0.000 claims description 2
- SJSFVUFHKYUAIF-UHFFFAOYSA-N (4-methyl-1,3-benzoxazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=C(C)C=CC=C2O1 SJSFVUFHKYUAIF-UHFFFAOYSA-N 0.000 claims description 2
- QGHMMSSRSVVVRM-UHFFFAOYSA-N (4-methyl-1h-benzimidazol-2-yl)-piperazin-1-ylmethanone Chemical compound N=1C=2C(C)=CC=CC=2NC=1C(=O)N1CCNCC1 QGHMMSSRSVVVRM-UHFFFAOYSA-N 0.000 claims description 2
- UBKBDXQCADGBAU-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[4-(propan-2-ylamino)-1h-benzimidazol-2-yl]methanone Chemical compound N=1C=2C(NC(C)C)=CC=CC=2NC=1C(=O)N1CCN(C)CC1 UBKBDXQCADGBAU-UHFFFAOYSA-N 0.000 claims description 2
- UHYCZMGQTVNZIL-UHFFFAOYSA-N (5,6-difluoro-1h-benzimidazol-2-yl)-(3-methylpiperazin-1-yl)methanone Chemical compound C1CNC(C)CN1C(=O)C1=NC2=CC(F)=C(F)C=C2N1 UHYCZMGQTVNZIL-UHFFFAOYSA-N 0.000 claims description 2
- KQCYNSQKCRQOBH-UHFFFAOYSA-N (5,6-difluoro-1h-benzimidazol-2-yl)-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=NC2=CC(F)=C(F)C=C2N1 KQCYNSQKCRQOBH-UHFFFAOYSA-N 0.000 claims description 2
- JVXIJSYPRSOIMJ-UHFFFAOYSA-N (7-methyl-1,3-benzoxazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC=CC(C)=C2O1 JVXIJSYPRSOIMJ-UHFFFAOYSA-N 0.000 claims description 2
- GTPFOQVEOMZTQO-UHFFFAOYSA-N 1,3-benzothiazol-2-yl-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC=CC=C2S1 GTPFOQVEOMZTQO-UHFFFAOYSA-N 0.000 claims description 2
- ZMYZAIFGDZEZEJ-UHFFFAOYSA-N 1,3-benzoxazol-2-yl-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC=CC=C2O1 ZMYZAIFGDZEZEJ-UHFFFAOYSA-N 0.000 claims description 2
- OBQMQANOQQJNFK-UHFFFAOYSA-N 4-methyl-1h-benzimidazole-2-carboxylic acid Chemical compound CC1=CC=CC2=C1N=C(C(O)=O)N2 OBQMQANOQQJNFK-UHFFFAOYSA-N 0.000 claims description 2
- VVCCUBBNXURKEE-UHFFFAOYSA-N 5,6-difluoro-1h-benzimidazole-2-carboxylic acid Chemical compound FC1=C(F)C=C2NC(C(=O)O)=NC2=C1 VVCCUBBNXURKEE-UHFFFAOYSA-N 0.000 claims description 2
- TYXHLKWWJIWESF-UHFFFAOYSA-N 6-fluoro-1h-benzimidazole-2-carboxylic acid Chemical compound C1=C(F)C=C2NC(C(=O)O)=NC2=C1 TYXHLKWWJIWESF-UHFFFAOYSA-N 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000018501 Lymphatic disease Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 208000018555 lymphatic system disease Diseases 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- XFOCDCVVEXCWCX-UHFFFAOYSA-N (4,5-dimethyl-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=C(C)C(C)=CC=C2N1 XFOCDCVVEXCWCX-UHFFFAOYSA-N 0.000 claims 1
- FJVRPDNNLDYOPB-UHFFFAOYSA-N (4,6-difluoro-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=C(F)C=C(F)C=C2N1 FJVRPDNNLDYOPB-UHFFFAOYSA-N 0.000 claims 1
- GYYBQBFFXKJAFU-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-(6-fluoro-1h-benzimidazol-2-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=NC2=CC(F)=CC=C2N1 GYYBQBFFXKJAFU-UHFFFAOYSA-N 0.000 claims 1
- DTXHWDXBLANYOU-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-(4-nitro-1h-benzimidazol-2-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=C([N+]([O-])=O)C=CC=C2N1 DTXHWDXBLANYOU-UHFFFAOYSA-N 0.000 claims 1
- CMBIJPNSXFXCIW-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-(6-nitro-1h-benzimidazol-2-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC([N+]([O-])=O)=CC=C2N1 CMBIJPNSXFXCIW-UHFFFAOYSA-N 0.000 claims 1
- DLODBVBWYZQNMJ-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[5-(trifluoromethoxy)-1,3-benzoxazol-2-yl]methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(OC(F)(F)F)=CC=C2O1 DLODBVBWYZQNMJ-UHFFFAOYSA-N 0.000 claims 1
- QXOOYTVOPSQVHZ-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(C(F)(F)F)=CC=C2S1 QXOOYTVOPSQVHZ-UHFFFAOYSA-N 0.000 claims 1
- LCVQWNHJNCLEFE-UHFFFAOYSA-N (5,6-dichloro-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(Cl)=C(Cl)C=C2N1 LCVQWNHJNCLEFE-UHFFFAOYSA-N 0.000 claims 1
- VGDHTVNHYVEPID-UHFFFAOYSA-N (5,6-dimethyl-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(C)=C(C)C=C2N1 VGDHTVNHYVEPID-UHFFFAOYSA-N 0.000 claims 1
- DPPNIYJDZSKSIQ-UHFFFAOYSA-N (5,7-difluoro-1,3-benzoxazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(F)=CC(F)=C2O1 DPPNIYJDZSKSIQ-UHFFFAOYSA-N 0.000 claims 1
- IAQXXQRUVZLWRM-UHFFFAOYSA-N (5-chloro-1,3-benzothiazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(Cl)=CC=C2S1 IAQXXQRUVZLWRM-UHFFFAOYSA-N 0.000 claims 1
- MCFJROXHMJOJDE-UHFFFAOYSA-N (6-bromo-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NC2=CC(Br)=CC=C2N1 MCFJROXHMJOJDE-UHFFFAOYSA-N 0.000 claims 1
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- 239000003623 enhancer Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims 1
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- ZVFSYTFFWGYEMM-UHFFFAOYSA-N 2-(trichloromethyl)-1h-benzimidazole Chemical compound C1=CC=C2NC(C(Cl)(Cl)Cl)=NC2=C1 ZVFSYTFFWGYEMM-UHFFFAOYSA-N 0.000 description 7
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- CTBHTPQCCMGLKI-UHFFFAOYSA-N 4-methyl-2-(trichloromethyl)-1h-benzimidazole Chemical compound CC1=CC=CC2=C1N=C(C(Cl)(Cl)Cl)N2 CTBHTPQCCMGLKI-UHFFFAOYSA-N 0.000 description 6
- GNKRJZXKNZQBJQ-UHFFFAOYSA-N 5,6-difluoro-2-(trichloromethyl)-1h-benzimidazole Chemical compound C1=C(F)C(F)=CC2=C1NC(C(Cl)(Cl)Cl)=N2 GNKRJZXKNZQBJQ-UHFFFAOYSA-N 0.000 description 6
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- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 6
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| MX354852B (es) | 2010-09-02 | 2018-03-22 | Suven Life Sciences Ltd Star | Compuestos de heterociclilo comoligandos del receptor h3 de la histamina. |
| US8859550B2 (en) | 2011-09-12 | 2014-10-14 | Kalypsys, Inc. | Heterocyclic inhibitors of histamine receptors for the treatment of disease |
| CN102512421B (zh) * | 2011-10-28 | 2013-11-06 | 中国科学院广州生物医药与健康研究院 | 哌嗪酰胺类化合物在制药中的应用 |
| KR101939710B1 (ko) | 2011-12-21 | 2019-01-17 | 노비라 테라퓨틱스, 인코포레이티드 | B형 간염의 항바이러스성 제제 |
| US9688989B2 (en) | 2012-06-08 | 2017-06-27 | Sensorion | H4 receptor inhibitors for treating tinnitus |
| KR20210081451A (ko) | 2012-08-28 | 2021-07-01 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 설파모일-아릴아미드 및 b형 간염 치료제로서의 그 용도 |
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| US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US9181288B2 (en) | 2014-01-16 | 2015-11-10 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| CA2936947A1 (en) | 2014-02-05 | 2015-08-13 | Novira Therapeutics, Inc. | Combination therapy for treatment of hbv infections |
| US11078193B2 (en) | 2014-02-06 | 2021-08-03 | Janssen Sciences Ireland Uc | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| WO2015127549A1 (en) * | 2014-02-27 | 2015-09-03 | Hassan Pajouhesh | Heterocyclic inhibitors of the sodium channel |
| US9400280B2 (en) | 2014-03-27 | 2016-07-26 | Novira Therapeutics, Inc. | Piperidine derivatives and methods of treating hepatitis B infections |
| JP2018510159A (ja) | 2015-03-19 | 2018-04-12 | ノヴィラ・セラピューティクス・インコーポレイテッド | アゾカン及びアゾナン誘導体及びｂ型肝炎感染症の治療法 |
| US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| JP6845231B2 (ja) | 2015-09-29 | 2021-03-17 | ノヴィラ・セラピューティクス・インコーポレイテッド | Ｂ型肝炎抗ウイルス薬の結晶形態 |
| JP2019511542A (ja) | 2016-04-15 | 2019-04-25 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | カプシド集合阻害剤を含む組み合わせ及び方法 |
| AU2019235522A1 (en) | 2018-03-14 | 2020-09-03 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator dosing regimen |
| US11096931B2 (en) | 2019-02-22 | 2021-08-24 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of HBV infection or HBV-induced diseases |
| AU2020269897A1 (en) | 2019-05-06 | 2021-10-14 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of HBV infection or HBV-induced diseases |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE791501A (fr) | 1971-11-19 | 1973-05-17 | Albert Ag Chem Werke | Diamines cycliques n,n'-disubstituees et leur procede de preparation |
| US4115569A (en) | 1971-11-19 | 1978-09-19 | Hoechst Aktiengesellschaft | Cyclic diamine derivatives |
| SU1074094A1 (ru) | 1982-07-30 | 1992-04-23 | Научно-исследовательский институт фармакологии АМН СССР | Гидрохлорид 4-бензилпиперазида 3-метилбензофуран-2-карбоновой кислоты, обладающий психотропной активностью |
| JPS5936670A (ja) | 1982-08-25 | 1984-02-28 | Takeda Chem Ind Ltd | ベンゾチアゾ−ル誘導体，その製造法およびそれを含有する摂食抑制剤 |
| US4490373A (en) * | 1983-05-20 | 1984-12-25 | Usv Pharmaceutical Corporation | Method of treating asthma |
| DE3708292A1 (de) | 1987-03-14 | 1988-09-29 | Basf Ag | Gegen einwirkung von licht stabilisierte polymere sowie neue imidazol-2-carbonsaeureanilide |
| JPH01132579A (ja) | 1987-11-19 | 1989-05-25 | Ss Pharmaceut Co Ltd | インドール誘導体 |
| US4937246A (en) | 1987-11-25 | 1990-06-26 | Takeda Chemical Industries, Ltd. | PAF antagonist, 1,4-disubstituted piperazine compounds and production thereof |
| DK733788A (da) | 1988-01-14 | 1989-07-15 | Fujisawa Pharmaceutical Co | Indolylpiperidinderivater og fremgangsmaade til fremstilling deraf |
| GB8827189D0 (en) | 1988-11-21 | 1988-12-29 | Fujisawa Pharmaceutical Co | 2(1h)-quinolinone compounds processes for preparation thereof & pharmaceutical composition comprising same |
| US5563142A (en) | 1989-12-28 | 1996-10-08 | The Upjohn Company | Diaromatic substituted compounds as anti-HIV-1 agents |
| AU654808B2 (en) | 1989-12-28 | 1994-11-24 | Pharmacia & Upjohn Company | Diaromatic substituted anti-aids compounds |
| HUT64320A (en) * | 1990-12-14 | 1993-12-28 | Merrell Dow Pharma | Process for production antiallergic imidazole derivatives and pharmaceutical preparations containing these compounds |
| JPH0525131A (ja) | 1991-07-17 | 1993-02-02 | Toray Ind Inc | インドール誘導体およびその医薬用途 |
| JPH05255089A (ja) | 1991-12-18 | 1993-10-05 | Sanwa Kagaku Kenkyusho Co Ltd | 抗ウイルス剤 |
| DE4307883A1 (en) | 1992-03-12 | 1993-09-23 | Westarp Martin Egon Dr Med | Use of anti-retroviral substances - to treat motor-neuronal diseases |
| WO1994009781A1 (en) | 1992-10-28 | 1994-05-11 | The Upjohn Company | Use of bhap compounds in combination with other non-nucleoside reverse transcriptase inhibitors for the treatment of hiv infection |
| AU6435594A (en) | 1993-04-15 | 1994-11-08 | Merck Sharp & Dohme Limited | Indole derivatives as dopamine d4 antagonists |
| FR2705095B1 (fr) | 1993-05-12 | 1995-06-23 | Adir | Nouveaux indoles substitués, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
| TW270114B (ja) | 1993-10-22 | 1996-02-11 | Hoffmann La Roche | |
| US5891902A (en) | 1994-01-18 | 1999-04-06 | Kyowa Hakko Kogyo Co., Ltd. | Indole derivatives |
| JPH09124631A (ja) | 1994-02-03 | 1997-05-13 | Shanxi Chuiyaku Kenkyuin | ベンゾフラン誘導体及びそれを含む医薬組成物 |
| WO1997003965A1 (fr) | 1995-07-18 | 1997-02-06 | Kyowa Hakko Kogyo Co., Ltd. | Derives d'indole |
| JPH09124609A (ja) | 1995-11-07 | 1997-05-13 | Nissan Chem Ind Ltd | ベンズイミダゾール誘導体 |
| TW593290B (en) | 1996-05-10 | 2004-06-21 | Janssen Pharmaceutica Nv | Alkylaminobenzothiazole and -benzoxazole derivatives |
| JPH09325131A (ja) | 1996-06-03 | 1997-12-16 | Japan Steel & Tube Constr Co Ltd | 隅肉溶接部探傷用磁化装置 |
| DE69730837T2 (de) | 1996-07-09 | 2005-09-29 | Nikem Research S.R.L., Baranzate Di Bollate | Indolderivate zur behandlung von osteoporose |
| CN1265660A (zh) | 1997-08-15 | 2000-09-06 | 辉瑞产品公司 | 2－(4－芳基或杂芳基－哌嗪－1－基甲基)－1h－吲哚衍生物 |
| WO1999058120A1 (en) | 1998-05-08 | 1999-11-18 | Rolf Berge | USE OF NON-β-OXIDIZABLE FATTY ACID ANALOGUES FOR TREATMENT OF SYNDROME-X CONDITIONS |
| EP0978512A1 (en) | 1998-07-29 | 2000-02-09 | Societe Civile Bioprojet | Non-imidazole aryloxy (or arylthio) alkylamines as histamine H3-receptor antagonists and their therapeutic applications |
| AU2001241927A1 (en) | 2000-02-28 | 2001-09-12 | Scios Inc. | Inhibitors of p38-alpha kinase |
| TWI288745B (en) | 2000-04-05 | 2007-10-21 | Daiichi Seiyaku Co | Ethylenediamine derivatives |
| JP2003104975A (ja) * | 2001-09-28 | 2003-04-09 | Sumitomo Pharmaceut Co Ltd | 新規なベンゾチアゾール化合物 |
-
2003
- 2003-09-04 WO PCT/US2003/027461 patent/WO2004022060A2/en active Application Filing
- 2003-09-04 US US10/655,381 patent/US7504426B2/en active Active
- 2003-09-04 RS YUP-2005/0201A patent/RS20050201A/sr unknown
- 2003-09-04 RU RU2005106274/04A patent/RU2005106274A/ru not_active Application Discontinuation
- 2003-09-04 KR KR1020057003818A patent/KR20050033662A/ko not_active Application Discontinuation
- 2003-09-04 NZ NZ538401A patent/NZ538401A/en unknown
- 2003-09-04 MX MXPA05002575A patent/MXPA05002575A/es unknown
- 2003-09-04 CA CA002497827A patent/CA2497827A1/en not_active Abandoned
- 2003-09-04 AU AU2003265886A patent/AU2003265886A1/en not_active Abandoned
- 2003-09-04 JP JP2004534443A patent/JP2006500390A/ja not_active Withdrawn
- 2003-09-04 UA UAA200503209A patent/UA79309C2/uk unknown
- 2003-09-04 CN CNA038249693A patent/CN1694704A/zh active Pending
- 2003-09-04 PL PL377087A patent/PL377087A1/pl not_active Application Discontinuation
- 2003-09-04 EP EP03794573A patent/EP1545532A2/en not_active Withdrawn
- 2003-09-04 BR BR0314059-8A patent/BR0314059A/pt not_active IP Right Cessation
- 2003-09-05 AR ARP030103235A patent/AR041170A1/es not_active Application Discontinuation
-
2005
- 2005-02-24 IS IS7716A patent/IS7716A/is unknown
- 2005-03-04 EC EC2005005647A patent/ECSP055647A/es unknown
- 2005-04-05 NO NO20051694A patent/NO20051694L/no not_active Application Discontinuation
- 2005-04-05 ZA ZA200502750A patent/ZA200502750B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO20051694L (no) | 2005-04-05 |
| IS7716A (is) | 2005-02-24 |
| WO2004022060A2 (en) | 2004-03-18 |
| EP1545532A2 (en) | 2005-06-29 |
| RU2005106274A (ru) | 2005-11-10 |
| KR20050033662A (ko) | 2005-04-12 |
| US20040058934A1 (en) | 2004-03-25 |
| AR041170A1 (es) | 2005-05-04 |
| AU2003265886A1 (en) | 2004-03-29 |
| RS20050201A (en) | 2007-06-04 |
| NZ538401A (en) | 2008-03-28 |
| PL377087A1 (pl) | 2006-01-23 |
| ECSP055647A (es) | 2005-05-30 |
| MXPA05002575A (es) | 2005-09-08 |
| WO2004022060A3 (en) | 2004-07-08 |
| US7504426B2 (en) | 2009-03-17 |
| CN1694704A (zh) | 2005-11-09 |
| ZA200502750B (en) | 2006-06-28 |
| WO2004022060A8 (en) | 2004-06-03 |
| BR0314059A (pt) | 2005-07-05 |
| CA2497827A1 (en) | 2004-03-18 |
| JP2006500390A (ja) | 2006-01-05 |
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