CA2701579A1 - Novel aryl potassium channel blockers and uses thereof - Google Patents
Novel aryl potassium channel blockers and uses thereof Download PDFInfo
- Publication number
- CA2701579A1 CA2701579A1 CA2701579A CA2701579A CA2701579A1 CA 2701579 A1 CA2701579 A1 CA 2701579A1 CA 2701579 A CA2701579 A CA 2701579A CA 2701579 A CA2701579 A CA 2701579A CA 2701579 A1 CA2701579 A1 CA 2701579A1
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- phenyl
- alkyl
- lower alkyl
- hydrogen
- 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
Links
- 125000003118 aryl group Chemical group 0.000 title description 27
- 239000003450 potassium channel blocker Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 206
- 238000000034 method Methods 0.000 claims abstract description 97
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 25
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 25
- 238000011282 treatment Methods 0.000 claims abstract description 22
- 230000002265 prevention Effects 0.000 claims abstract description 15
- 230000000694 effects Effects 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 102000004257 Potassium Channel Human genes 0.000 claims abstract description 12
- 108020001213 potassium channel Proteins 0.000 claims abstract description 12
- 230000001363 autoimmune Effects 0.000 claims abstract description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 129
- 125000001072 heteroaryl group Chemical group 0.000 claims description 96
- 150000003839 salts Chemical class 0.000 claims description 84
- 125000003107 substituted aryl group Chemical group 0.000 claims description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims description 81
- 239000001257 hydrogen Substances 0.000 claims description 81
- 125000000623 heterocyclic group Chemical group 0.000 claims description 80
- -1 1,3,5-trithianyl Chemical group 0.000 claims description 71
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 55
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 51
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 51
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 51
- 150000002431 hydrogen Chemical group 0.000 claims description 43
- 125000005843 halogen group Chemical group 0.000 claims description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 19
- 125000002947 alkylene group Chemical group 0.000 claims description 18
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 18
- 125000005647 linker group Chemical group 0.000 claims description 18
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims description 17
- 125000004104 aryloxy group Chemical group 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 210000000056 organ Anatomy 0.000 claims description 8
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 7
- 208000037979 autoimmune inflammatory disease Diseases 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 208000037976 chronic inflammation Diseases 0.000 claims description 7
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000001425 triazolyl group Chemical group 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 4
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 4
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000003838 furazanyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 3
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 3
- HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 claims description 3
- 108010072051 Glatiramer Acetate Proteins 0.000 claims description 3
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 229960003776 glatiramer acetate Drugs 0.000 claims description 3
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 3
- 229960001156 mitoxantrone Drugs 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 229960005027 natalizumab Drugs 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 3
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 3
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 claims description 2
- JVYQJZLNAIRPMD-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)propoxy]-4-methoxy-2-methyl-6-(2-morpholin-4-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1CCCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCOCC1 JVYQJZLNAIRPMD-UHFFFAOYSA-N 0.000 claims description 2
- 125000005987 1-oxo-thiomorpholinyl group Chemical group 0.000 claims description 2
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 229960004461 interferon beta-1a Drugs 0.000 claims description 2
- 229960003161 interferon beta-1b Drugs 0.000 claims description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
- 230000001506 immunosuppresive effect Effects 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- GSPMMBYLSBPDPD-UHFFFAOYSA-N 1-[2-[2-(cyclopentylamino)ethoxy]-3-[3-(4-fluorophenyl)butoxy]-4-methoxy-5,6-dimethylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(C)C(C)=C(C(C)=O)C=1OCCNC1CCCC1 GSPMMBYLSBPDPD-UHFFFAOYSA-N 0.000 claims 1
- RQHPSRVBUFJHPD-UHFFFAOYSA-N 1-[2-[2-acetyl-4-chloro-5-methoxy-3-methyl-6-(3-phenylpropoxy)phenoxy]ethyl]azetidin-3-one Chemical compound C=1C=CC=CC=1CCCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CC(=O)C1 RQHPSRVBUFJHPD-UHFFFAOYSA-N 0.000 claims 1
- CGRRNHLPSQSHLB-UHFFFAOYSA-N 1-[2-[2-acetyl-4-chloro-6-[3-(4-fluorophenyl)butoxy]-5-methoxy-3-methylphenoxy]ethyl]piperidin-4-one Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCC(=O)CC1 CGRRNHLPSQSHLB-UHFFFAOYSA-N 0.000 claims 1
- JQRJTRBEMHMVHZ-UHFFFAOYSA-N 1-[3-chloro-4-methoxy-2-methyl-5-(3-phenylpropoxy)-6-(2-thiomorpholin-4-ylethoxy)phenyl]ethanone Chemical compound C=1C=CC=CC=1CCCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCSCC1 JQRJTRBEMHMVHZ-UHFFFAOYSA-N 0.000 claims 1
- XRLDXFLSAONSJB-UHFFFAOYSA-N 1-[3-chloro-4-methoxy-2-methyl-5-(4-phenylbutyl)-6-(2-pyridin-2-ylethoxy)phenyl]ethanone Chemical compound C=1C=CC=CC=1CCCCC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCC1=CC=CC=N1 XRLDXFLSAONSJB-UHFFFAOYSA-N 0.000 claims 1
- AFXQWYJUTLZZCT-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-(2-morpholin-4-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCOCC1 AFXQWYJUTLZZCT-UHFFFAOYSA-N 0.000 claims 1
- MPKHVTUVOYVYHX-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-(2-piperidin-1-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCCCC1 MPKHVTUVOYVYHX-UHFFFAOYSA-N 0.000 claims 1
- SDZCAOTUJXNNED-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-(2-pyrazin-2-yloxyethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCOC1=CN=CC=N1 SDZCAOTUJXNNED-UHFFFAOYSA-N 0.000 claims 1
- LMABIUNSRMPZEJ-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-(2-pyridin-2-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCC1=CC=CC=N1 LMABIUNSRMPZEJ-UHFFFAOYSA-N 0.000 claims 1
- RHHDNRDBTLFLTK-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-(3-morpholin-4-ylpropoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCCN1CCOCC1 RHHDNRDBTLFLTK-UHFFFAOYSA-N 0.000 claims 1
- KOMPETZPHDRUMU-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-(pyridin-2-ylmethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCC1=CC=CC=N1 KOMPETZPHDRUMU-UHFFFAOYSA-N 0.000 claims 1
- PGUGAUHBYMMBMG-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-[2-(1,2,4-triazol-1-yl)ethoxy]phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1C=NC=N1 PGUGAUHBYMMBMG-UHFFFAOYSA-N 0.000 claims 1
- QLYZKQPIZSEMBB-ZVAWYAOSSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-[2-[(3s)-3-methylmorpholin-4-yl]ethoxy]phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCOC[C@@H]1C QLYZKQPIZSEMBB-ZVAWYAOSSA-N 0.000 claims 1
- OWKPEMVKNFBFNL-UHFFFAOYSA-N 1-[3-chloro-5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2-methyl-6-[3-(1-oxo-1,4-thiazinan-4-yl)propoxy]phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCCN1CCS(=O)CC1 OWKPEMVKNFBFNL-UHFFFAOYSA-N 0.000 claims 1
- KXTCDYKQXOIIER-UHFFFAOYSA-N 1-[3-chloro-5-[4-(4-fluorophenyl)pentyl]-4-methoxy-2-methyl-6-(2-morpholin-4-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCCC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCOCC1 KXTCDYKQXOIIER-UHFFFAOYSA-N 0.000 claims 1
- FOXXBOZZEZOPJH-UHFFFAOYSA-N 1-[3-chloro-5-[4-(4-fluorophenyl)pentyl]-4-methoxy-2-methyl-6-(2-pyridin-2-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCCC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCC1=CC=CC=N1 FOXXBOZZEZOPJH-UHFFFAOYSA-N 0.000 claims 1
- XVIBLMUDQBTZKO-UHFFFAOYSA-N 1-[4-methoxy-6-methyl-2-(2-morpholin-4-ylethoxy)-3-(3-phenylpropoxy)phenyl]ethanone Chemical compound C=1C=CC=CC=1CCCOC=1C(OC)=CC(C)=C(C(C)=O)C=1OCCN1CCOCC1 XVIBLMUDQBTZKO-UHFFFAOYSA-N 0.000 claims 1
- ACEMEYWSGDXKJA-UHFFFAOYSA-N 1-[5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2,3-dimethyl-6-(2-morpholin-4-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(C)C(C)=C(C(C)=O)C=1OCCN1CCOCC1 ACEMEYWSGDXKJA-UHFFFAOYSA-N 0.000 claims 1
- CILRSKCBTLHOIZ-UHFFFAOYSA-N 1-[5-[3-(4-fluorophenyl)butoxy]-4-methoxy-2,3-dimethyl-6-(2-pyridin-2-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(C)C(C)=C(C(C)=O)C=1OCCC1=CC=CC=N1 CILRSKCBTLHOIZ-UHFFFAOYSA-N 0.000 claims 1
- PMJWSQWEHYPHNW-UHFFFAOYSA-N 1-[5-[3-(4-fluorophenyl)propoxy]-4-methoxy-2,3-dimethyl-6-(2-morpholin-4-ylethoxy)phenyl]ethanone Chemical compound C=1C=C(F)C=CC=1CCCOC=1C(OC)=C(C)C(C)=C(C(C)=O)C=1OCCN1CCOCC1 PMJWSQWEHYPHNW-UHFFFAOYSA-N 0.000 claims 1
- PHHHJHHNFPOTRT-UHFFFAOYSA-N 1-[5-chloro-2-[2-(3,3-difluoroazetidin-1-yl)ethoxy]-3-[3-(4-fluorophenyl)butoxy]-4-methoxy-6-methylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CC(F)(F)C1 PHHHJHHNFPOTRT-UHFFFAOYSA-N 0.000 claims 1
- TUEIEJCESFKYPU-UHFFFAOYSA-N 1-[5-chloro-2-[2-(3,3-difluoroazetidin-1-yl)ethoxy]-4-methoxy-6-methyl-3-(3-phenylpropoxy)phenyl]ethanone Chemical compound C=1C=CC=CC=1CCCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CC(F)(F)C1 TUEIEJCESFKYPU-UHFFFAOYSA-N 0.000 claims 1
- KBCOVKKZKQHXKQ-UHFFFAOYSA-N 1-[5-chloro-2-[2-(3,3-difluoropiperidin-1-yl)ethoxy]-3-[3-(4-fluorophenyl)butoxy]-4-methoxy-6-methylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCCC(F)(F)C1 KBCOVKKZKQHXKQ-UHFFFAOYSA-N 0.000 claims 1
- BHGUSJZLADDXGG-UHFFFAOYSA-N 1-[5-chloro-2-[2-(3,3-difluoropyrrolidin-1-yl)ethoxy]-4-methoxy-6-methyl-3-(3-phenylpropoxy)phenyl]ethanone Chemical compound C=1C=CC=CC=1CCCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCC(F)(F)C1 BHGUSJZLADDXGG-UHFFFAOYSA-N 0.000 claims 1
- YJOSRRCHKXMTAA-UHFFFAOYSA-N 1-[5-chloro-2-[2-(3-hydroxyazetidin-1-yl)ethoxy]-4-methoxy-6-methyl-3-(3-phenylpropoxy)phenyl]ethanone Chemical compound C=1C=CC=CC=1CCCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CC(O)C1 YJOSRRCHKXMTAA-UHFFFAOYSA-N 0.000 claims 1
- YCYCGOUZGYWODG-UHFFFAOYSA-N 1-[5-chloro-2-[2-(4,4-difluoropiperidin-1-yl)ethoxy]-3-[3-(4-fluorophenyl)butoxy]-4-methoxy-6-methylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCC(F)(F)CC1 YCYCGOUZGYWODG-UHFFFAOYSA-N 0.000 claims 1
- JLISGBOIDPFSRD-UHFFFAOYSA-N 1-[5-chloro-2-[2-(cyclopentylamino)ethoxy]-3-[3-(4-fluorophenyl)butoxy]-4-methoxy-6-methylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCNC1CCCC1 JLISGBOIDPFSRD-UHFFFAOYSA-N 0.000 claims 1
- SJMHDSOPXSARFU-UHFFFAOYSA-N 1-[5-chloro-2-[2-(cyclopentylamino)ethoxy]-4-methoxy-6-methyl-3-(3-phenylpropoxy)phenyl]ethanone Chemical compound C=1C=CC=CC=1CCCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCNC1CCCC1 SJMHDSOPXSARFU-UHFFFAOYSA-N 0.000 claims 1
- MBLFTTRVTPTPIA-UHFFFAOYSA-N 1-[5-chloro-2-[2-(dimethylamino)ethoxy]-3-[3-(4-fluorophenyl)butoxy]-4-methoxy-6-methylphenyl]ethanone Chemical compound COC1=C(Cl)C(C)=C(C(C)=O)C(OCCN(C)C)=C1OCCC(C)C1=CC=C(F)C=C1 MBLFTTRVTPTPIA-UHFFFAOYSA-N 0.000 claims 1
- VEAPPFBWEHILQO-UHFFFAOYSA-N 1-[5-chloro-2-[3-(1,1-dioxo-1,4-thiazinan-4-yl)propoxy]-3-[3-(4-fluorophenyl)butoxy]-4-methoxy-6-methylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCCN1CCS(=O)(=O)CC1 VEAPPFBWEHILQO-UHFFFAOYSA-N 0.000 claims 1
- AKEYKAZDWGUJMH-UHFFFAOYSA-N 1-[5-chloro-3-[3-(4-fluorophenyl)butoxy]-2-(2-imidazol-1-ylethoxy)-4-methoxy-6-methylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1C=CN=C1 AKEYKAZDWGUJMH-UHFFFAOYSA-N 0.000 claims 1
- IRIXQIIFKKDDTC-UHFFFAOYSA-N 1-[5-chloro-3-[3-(4-fluorophenyl)butoxy]-2-[2-(4-hydroxypiperidin-1-yl)ethoxy]-4-methoxy-6-methylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CCC(O)CC1 IRIXQIIFKKDDTC-UHFFFAOYSA-N 0.000 claims 1
- APEZGFTUXCOSNT-CAWMZFRYSA-N 1-[5-chloro-3-[3-(4-fluorophenyl)butoxy]-2-[2-[(3r)-3-fluoropyrrolidin-1-yl]ethoxy]-4-methoxy-6-methylphenyl]ethanone Chemical compound C=1C=C(F)C=CC=1C(C)CCOC=1C(OC)=C(Cl)C(C)=C(C(C)=O)C=1OCCN1CC[C@@H](F)C1 APEZGFTUXCOSNT-CAWMZFRYSA-N 0.000 claims 1
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Classifications
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
- C07C217/18—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
- C07C217/22—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by carbon atoms having at least two bonds to oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
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- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/38—Halogen atoms or nitro radicals
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- C07—ORGANIC CHEMISTRY
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/60—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/18—Oxygen or sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| PCT/AU2008/001480 WO2009043117A1 (en) | 2007-10-04 | 2008-10-03 | Novel aryl potassium channel blockers and uses thereof |
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| US9493451B2 (en) | 2011-05-16 | 2016-11-15 | Bionomics Limited | Amine derivatives as potassium channel blockers |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US9556132B2 (en) * | 2012-06-25 | 2017-01-31 | Saniona A/S | Tetrazole derivatives and their use as potassium channel modulators |
| US10118890B2 (en) | 2014-10-10 | 2018-11-06 | The Research Foundation For The State University Of New York | Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration |
| TWI698438B (zh) | 2015-03-13 | 2020-07-11 | 德商4Sc製藥公司 | Kv1.3抑制劑及其醫學應用 |
| TWI701249B (zh) | 2015-03-13 | 2020-08-11 | 德商4Sc製藥公司 | Kv1.3抑制劑及其醫學應用 |
| CA3157026A1 (en) * | 2019-10-07 | 2021-04-15 | D.E. Shaw Research, Llc | Arylmethylene aromatic compounds as kv1.3 potassium shaker channel blockers |
| MX2022004127A (es) * | 2019-10-07 | 2022-06-14 | De Shaw Res Llc | Compuestos heterociclicos de arilo como bloqueadores del canal de potasio tipo shaker kv1.3. |
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| US5017572A (en) | 1988-04-22 | 1991-05-21 | Delalande S.A. | Derivatives of 1-[3-(4-hydroxyphenyl) 1-hydroxy 1-propyl] benzene substituted in position 2 by an aminoalkyleneoxy chain, the method of preparing same and the application thereof to therapeutics |
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| US5494895A (en) * | 1993-07-22 | 1996-02-27 | Merck & Co., Inc. | Scorpion peptide margatoxin with immunosuppressant activity |
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| WO1998023639A2 (en) * | 1996-11-27 | 1998-06-04 | University Of Florida | ShK TOXIN COMPOSITIONS AND METHODS OF USE |
| JPH10316853A (ja) | 1997-05-15 | 1998-12-02 | Sumitomo Bakelite Co Ltd | 半導体多層配線用層間絶縁膜樹脂組成物及び該絶縁膜の製造方法 |
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| US20030065039A1 (en) * | 1997-06-26 | 2003-04-03 | Statens Serum Institute | Biologically active 1,3-bis-aromatic-prop-2-en-1-ones, 1,3-bis-aromatic-propan-1-ones, and 1,3-bis-aromatic-prop-2-yn-1-ones |
| US6051590A (en) * | 1999-05-13 | 2000-04-18 | Merck & Co., Inc. | Immunosuppressant tricyclic compounds |
| AU2003224672B2 (en) * | 2002-03-08 | 2010-02-04 | Eisai R&D Management Co., Ltd. | Macrocyclic compounds useful as pharmaceuticals |
| US7915306B2 (en) * | 2002-03-08 | 2011-03-29 | Eisai Co., Ltd. | Macrocyclic compounds useful as pharmaceuticals |
| AUPS110302A0 (en) | 2002-03-14 | 2002-04-18 | Biomolecular Research Institute Limited | Novel chalcone derivatives and uses thereof |
| AUPS127202A0 (en) * | 2002-03-20 | 2002-04-18 | Walter And Eliza Hall Institute Of Medical Research, The | Therapeutic ion channel blocking agents and methods of use thereof |
| US7557138B2 (en) * | 2004-10-04 | 2009-07-07 | The Regents Of The University Of California | 5-phenoxyalkoxypsoralens and methods for selective inhibition of the voltage gated Kv1.3 potassium channel |
| US8063093B2 (en) * | 2005-03-15 | 2011-11-22 | Andrew J Harvey | Potassium channel blockers and uses thereof |
| NZ575685A (en) | 2006-10-04 | 2012-04-27 | Bionomics Ltd | Novel benzofuran potassium channel blockers and uses thereof |
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| US20100297077A1 (en) | 2010-11-25 |
| EP2197832A1 (en) | 2010-06-23 |
| WO2009043117A1 (en) | 2009-04-09 |
| EP2197832A4 (en) | 2013-10-30 |
| MX2010003541A (es) | 2010-08-09 |
| BRPI0817520A2 (pt) | 2015-08-18 |
| EA201070420A1 (ru) | 2010-10-29 |
| KR20100087148A (ko) | 2010-08-03 |
| US8202513B2 (en) | 2012-06-19 |
| AU2008307075B2 (en) | 2012-05-17 |
| ZA201002385B (en) | 2011-06-29 |
| JP2010540569A (ja) | 2010-12-24 |
| CN101888989A (zh) | 2010-11-17 |
| AU2008307075A1 (en) | 2009-04-09 |
| NZ584480A (en) | 2011-08-26 |
| IL204857A0 (en) | 2010-11-30 |
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| FZDE | Discontinued |
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