ES3000437T3 - Process for the preparation of clc-1 chloride channel inhibitors - Google Patents
Process for the preparation of clc-1 chloride channel inhibitors Download PDFInfo
- Publication number
- ES3000437T3 ES3000437T3 ES20734157T ES20734157T ES3000437T3 ES 3000437 T3 ES3000437 T3 ES 3000437T3 ES 20734157 T ES20734157 T ES 20734157T ES 20734157 T ES20734157 T ES 20734157T ES 3000437 T3 ES3000437 T3 ES 3000437T3
- Authority
- ES
- Spain
- Prior art keywords
- phenoxy
- dihydroisoxazol
- bromo
- butoxy
- propanoate
- 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.)
- Active
Links
- 108010062745 Chloride Channels Proteins 0.000 title claims abstract description 11
- 102000011045 Chloride Channels Human genes 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims description 34
- 239000003112 inhibitor Substances 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 61
- -1 (2S)-2-[4-bromo-2-(5-cyclopropyl-4-butoxy-4,5-dihydroisoxazol-3-yl)phenoxy]propanoate Chemical compound 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 239000011541 reaction mixture Substances 0.000 claims description 18
- 101710091665 Chloride channel protein 1 Proteins 0.000 claims description 17
- 102100023457 Chloride channel protein 1 Human genes 0.000 claims description 17
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 16
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 229910052805 deuterium Inorganic materials 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- 239000003960 organic solvent Substances 0.000 claims description 13
- 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 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 8
- 235000011054 acetic acid Nutrition 0.000 claims description 8
- 235000019253 formic acid Nutrition 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- XKXLEZCOELWNMB-ZETCQYMHSA-N BrC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC=C1 Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC=C1 XKXLEZCOELWNMB-ZETCQYMHSA-N 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 5
- FHZDWCKVAFRSJT-VPHXOMNUSA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOCC1OCCCC FHZDWCKVAFRSJT-VPHXOMNUSA-N 0.000 claims description 5
- GNWNRVOQGALFMS-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)O)C=C1)C1=NOC=C1 Chemical compound BrC1=CC(=C(OCC(=O)O)C=C1)C1=NOC=C1 GNWNRVOQGALFMS-UHFFFAOYSA-N 0.000 claims description 4
- ZXIRTXJWIFAJIW-LURJTMIESA-N BrC1=CC(=C(O[C@H](C(=O)O)C)C=C1F)C1=NOC=C1 Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)C)C=C1F)C1=NOC=C1 ZXIRTXJWIFAJIW-LURJTMIESA-N 0.000 claims description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- TTWJKNQPORDJFK-LJLKPOLSSA-N ethyl (2S)-2-[2-(4-butoxy-5-cyclopropyl-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOC(C1OCCCC)C1CC1 TTWJKNQPORDJFK-LJLKPOLSSA-N 0.000 claims description 4
- UYQLDUXNYVMFEJ-HKALDPMFSA-N ethyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOCC1OCCCC UYQLDUXNYVMFEJ-HKALDPMFSA-N 0.000 claims description 4
- LBXRECHFJGKDPG-LJLKPOLSSA-N ethyl (2S)-2-[4-bromo-2-(4-butoxy-5-cyclopropyl-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOC(C1OCCCC)C1CC1 LBXRECHFJGKDPG-LJLKPOLSSA-N 0.000 claims description 4
- OWWFKCQYQAMGPU-XYEKJYRLSA-N ethyl (2S)-2-[4-bromo-2-(4-butoxy-5-methyl-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOC(C1OCCCC)C OWWFKCQYQAMGPU-XYEKJYRLSA-N 0.000 claims description 4
- PODPFADCONKTCX-XLLULAGJSA-N ethyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOCC1OCC PODPFADCONKTCX-XLLULAGJSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- UNJXQCWLNLASCX-RMEHTXHKSA-N methyl (2S)-2-[2-(4-butoxy-5-cyclopropyl-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOC(C1OCCCC)C1CC1 UNJXQCWLNLASCX-RMEHTXHKSA-N 0.000 claims description 4
- RDTRMZHLACSQJV-LLTODGECSA-N methyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOCC1OCC RDTRMZHLACSQJV-LLTODGECSA-N 0.000 claims description 4
- AQRJKBKGHQBPFV-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)O)C=C1F)C1=NOC=C1 Chemical compound BrC1=CC(=C(OCC(=O)O)C=C1F)C1=NOC=C1 AQRJKBKGHQBPFV-UHFFFAOYSA-N 0.000 claims description 3
- ISEDOJMEEYNECG-ZDUSSCGKSA-N BrC1=CC(=C(O[C@H](C(=O)O)C(C)C)C=C1)C1=NOC=C1 Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)C(C)C)C=C1)C1=NOC=C1 ISEDOJMEEYNECG-ZDUSSCGKSA-N 0.000 claims description 3
- BFYVTTIOKWWEOA-QMMMGPOBSA-N BrC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC(=C1)C Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC(=C1)C BFYVTTIOKWWEOA-QMMMGPOBSA-N 0.000 claims description 3
- ITRJNEMJZZXLRM-QMMMGPOBSA-N BrC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC(=C1)C1CC1 Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC(=C1)C1CC1 ITRJNEMJZZXLRM-QMMMGPOBSA-N 0.000 claims description 3
- JNMCYSZTXWCMNG-ZDUSSCGKSA-N BrC1=CC(=C(O[C@H](C(=O)O)C2CC2)C=C1F)C1=NOC=C1 Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)C2CC2)C=C1F)C1=NOC=C1 JNMCYSZTXWCMNG-ZDUSSCGKSA-N 0.000 claims description 3
- WUPZUNIYCZNBOE-NSHDSACASA-N BrC1=CC(=C(O[C@H](C(=O)O)CC)C=C1)C1=NOC=C1 Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)CC)C=C1)C1=NOC=C1 WUPZUNIYCZNBOE-NSHDSACASA-N 0.000 claims description 3
- GKUXGKWHGMEHTK-AWEZNQCLSA-N BrC1=CC(=C(O[C@H](C(=O)O)CC2CC2)C=C1)C1=NOC=C1 Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)CC2CC2)C=C1)C1=NOC=C1 GKUXGKWHGMEHTK-AWEZNQCLSA-N 0.000 claims description 3
- MNOAVHGEVVUZAT-HNNXBMFYSA-N BrC1=CC(=C(O[C@H](C(=O)O)CC2CCC2)C=C1)C1=NOC=C1 Chemical compound BrC1=CC(=C(O[C@H](C(=O)O)CC2CCC2)C=C1)C1=NOC=C1 MNOAVHGEVVUZAT-HNNXBMFYSA-N 0.000 claims description 3
- IWZUPBMQNCHHMD-ZDUSSCGKSA-N ClC1=CC(=C(O[C@H](C(=O)O)C(C)C)C=C1)C1=NOC=C1 Chemical compound ClC1=CC(=C(O[C@H](C(=O)O)C(C)C)C=C1)C1=NOC=C1 IWZUPBMQNCHHMD-ZDUSSCGKSA-N 0.000 claims description 3
- BBQVYVKHXOWWCA-QMMMGPOBSA-N ClC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC(=C1)C1CC1 Chemical compound ClC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC(=C1)C1CC1 BBQVYVKHXOWWCA-QMMMGPOBSA-N 0.000 claims description 3
- JMNDVCMRYUTDPH-ZETCQYMHSA-N ClC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC=C1 Chemical compound ClC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC=C1 JMNDVCMRYUTDPH-ZETCQYMHSA-N 0.000 claims description 3
- BKGZPEYHVWBXLZ-LURJTMIESA-N ClC1=CC(=C(O[C@H](C(=O)O)C)C=C1Cl)C1=NOC=C1 Chemical compound ClC1=CC(=C(O[C@H](C(=O)O)C)C=C1Cl)C1=NOC=C1 BKGZPEYHVWBXLZ-LURJTMIESA-N 0.000 claims description 3
- YUPATJBREDABJA-LURJTMIESA-N ClC1=CC(=C(O[C@H](C(=O)O)C)C=C1F)C1=NOC=C1 Chemical compound ClC1=CC(=C(O[C@H](C(=O)O)C)C=C1F)C1=NOC=C1 YUPATJBREDABJA-LURJTMIESA-N 0.000 claims description 3
- GHYYQYSDIXWQSP-NSHDSACASA-N ClC1=CC(=C(O[C@H](C(=O)O)CC)C=C1)C1=NOC=C1 Chemical compound ClC1=CC(=C(O[C@H](C(=O)O)CC)C=C1)C1=NOC=C1 GHYYQYSDIXWQSP-NSHDSACASA-N 0.000 claims description 3
- LENFFRLIEYKHEW-AWEZNQCLSA-N ClC1=CC(=C(O[C@H](C(=O)O)CC2CC2)C=C1)C1=NOC=C1 Chemical compound ClC1=CC(=C(O[C@H](C(=O)O)CC2CC2)C=C1)C1=NOC=C1 LENFFRLIEYKHEW-AWEZNQCLSA-N 0.000 claims description 3
- ZZLHVSFELRPCIW-ZETCQYMHSA-N FC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC=C1 Chemical compound FC1=CC(=C(O[C@H](C(=O)O)C)C=C1)C1=NOC=C1 ZZLHVSFELRPCIW-ZETCQYMHSA-N 0.000 claims description 3
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 3
- 229940011051 isopropyl acetate Drugs 0.000 claims description 3
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 3
- AHPADEYJQOSJIB-RMEHTXHKSA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-5-cyclopropyl-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOC(C1OCCCC)C1CC1 AHPADEYJQOSJIB-RMEHTXHKSA-N 0.000 claims description 3
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- SLVJKZBQFCROOG-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)OC)C=C1)C1=NOCC1OCCCC Chemical compound BrC1=CC(=C(OCC(=O)OC)C=C1)C1=NOCC1OCCCC SLVJKZBQFCROOG-UHFFFAOYSA-N 0.000 claims description 2
- AEQALCSMLGHFMO-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)OC)C=C1F)C1=NOCC1OCC Chemical compound BrC1=CC(=C(OCC(=O)OC)C=C1F)C1=NOCC1OCC AEQALCSMLGHFMO-UHFFFAOYSA-N 0.000 claims description 2
- DJJUDSHIUGCALF-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)OC)C=C1F)C1=NOCC1OCCCC Chemical compound BrC1=CC(=C(OCC(=O)OC)C=C1F)C1=NOCC1OCCCC DJJUDSHIUGCALF-UHFFFAOYSA-N 0.000 claims description 2
- MOTMBCNGPAFOIP-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)OCC)C=C1)C1=NOCC1OCC Chemical compound BrC1=CC(=C(OCC(=O)OCC)C=C1)C1=NOCC1OCC MOTMBCNGPAFOIP-UHFFFAOYSA-N 0.000 claims description 2
- NHZQWGYPFIGKRR-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)OCC)C=C1)C1=NOCC1OCCCC Chemical compound BrC1=CC(=C(OCC(=O)OCC)C=C1)C1=NOCC1OCCCC NHZQWGYPFIGKRR-UHFFFAOYSA-N 0.000 claims description 2
- ZTHVHSCSZOTRSN-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)OCC)C=C1F)C1=NOCC1OCC Chemical compound BrC1=CC(=C(OCC(=O)OCC)C=C1F)C1=NOCC1OCC ZTHVHSCSZOTRSN-UHFFFAOYSA-N 0.000 claims description 2
- JDEUPLCPBDSYPL-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)OCC)C=C1F)C1=NOCC1OCCCC Chemical compound BrC1=CC(=C(OCC(=O)OCC)C=C1F)C1=NOCC1OCCCC JDEUPLCPBDSYPL-UHFFFAOYSA-N 0.000 claims description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- OZWNYMLRXZHYID-CHPOKUKFSA-N ethyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4,5-dichlorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1Cl)C1=NOCC1OCCCC OZWNYMLRXZHYID-CHPOKUKFSA-N 0.000 claims description 2
- XHOAQDCYDVNFSZ-CHPOKUKFSA-N ethyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chloro-5-fluorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1F)C1=NOCC1OCCCC XHOAQDCYDVNFSZ-CHPOKUKFSA-N 0.000 claims description 2
- NNNCPPRMCFAZJR-OYKVQYDMSA-N ethyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]-3-cyclopropylpropanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)CC2CC2)C=C1)C1=NOCC1OCCCC NNNCPPRMCFAZJR-OYKVQYDMSA-N 0.000 claims description 2
- OBEDCABYQFONBD-NNBQYGFHSA-N ethyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]-3-methylbutanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C(C)C)C=C1)C1=NOCC1OCCCC OBEDCABYQFONBD-NNBQYGFHSA-N 0.000 claims description 2
- HMYRBNSTFKKTRG-MYJWUSKBSA-N ethyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]butanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)CC)C=C1)C1=NOCC1OCCCC HMYRBNSTFKKTRG-MYJWUSKBSA-N 0.000 claims description 2
- QCKJHPBJEFPPAQ-HKALDPMFSA-N ethyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOCC1OCCCC QCKJHPBJEFPPAQ-HKALDPMFSA-N 0.000 claims description 2
- RVDVFEADYHNFLY-HKALDPMFSA-N ethyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-fluorophenoxy]propanoate Chemical compound FC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOCC1OCCCC RVDVFEADYHNFLY-HKALDPMFSA-N 0.000 claims description 2
- IACNVLFZJFWXRE-XLLULAGJSA-N ethyl (2S)-2-[2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-fluorophenoxy]propanoate Chemical compound FC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOCC1OCC IACNVLFZJFWXRE-XLLULAGJSA-N 0.000 claims description 2
- QSLVJSVNAXKCQH-CUVJYRNJSA-N ethyl (2S)-2-[4,5-dichloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1Cl)C1=NOCC1OCC QSLVJSVNAXKCQH-CUVJYRNJSA-N 0.000 claims description 2
- MHJQOAITGNOFFB-NNBQYGFHSA-N ethyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]-2-cyclopropylacetate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C2CC2)C=C1F)C1=NOCC1OCCCC MHJQOAITGNOFFB-NNBQYGFHSA-N 0.000 claims description 2
- WGCQFKPTOIVUMI-CHPOKUKFSA-N ethyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1F)C1=NOCC1OCCCC WGCQFKPTOIVUMI-CHPOKUKFSA-N 0.000 claims description 2
- HPNYBRCGKHKPQV-XJDOXCRVSA-N ethyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclobutylpropanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)CC2CCC2)C=C1)C1=NOCC1OCCCC HPNYBRCGKHKPQV-XJDOXCRVSA-N 0.000 claims description 2
- WOPJDVMTEYXBPS-NNBQYGFHSA-N ethyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-methylbutanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C(C)C)C=C1)C1=NOCC1OCCCC WOPJDVMTEYXBPS-NNBQYGFHSA-N 0.000 claims description 2
- PLFAZCQWRRXMSB-MYJWUSKBSA-N ethyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]butanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)CC)C=C1)C1=NOCC1OCCCC PLFAZCQWRRXMSB-MYJWUSKBSA-N 0.000 claims description 2
- FNANGBLHGRBYJO-LWKPJOBUSA-N ethyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]-2-cyclopropylacetate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C2CC2)C=C1F)C1=NOCC1OCC FNANGBLHGRBYJO-LWKPJOBUSA-N 0.000 claims description 2
- GZYRYZDUYIAOMT-CUVJYRNJSA-N ethyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1F)C1=NOCC1OCC GZYRYZDUYIAOMT-CUVJYRNJSA-N 0.000 claims description 2
- MGHGIJBIFSTORN-ZENAZSQFSA-N ethyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclobutylpropanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)CC2CCC2)C=C1)C1=NOCC1OCC MGHGIJBIFSTORN-ZENAZSQFSA-N 0.000 claims description 2
- VGOGUKISXZDYHT-BHWOMJMDSA-N ethyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclopropylpropanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)CC2CC2)C=C1)C1=NOCC1OCC VGOGUKISXZDYHT-BHWOMJMDSA-N 0.000 claims description 2
- CZSMTDHKVRLKII-LWKPJOBUSA-N ethyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-methylbutanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)C(C)C)C=C1)C1=NOCC1OCC CZSMTDHKVRLKII-LWKPJOBUSA-N 0.000 claims description 2
- BWDKIVIRQYNWCO-CFMCSPIPSA-N ethyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]butanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OCC)CC)C=C1)C1=NOCC1OCC BWDKIVIRQYNWCO-CFMCSPIPSA-N 0.000 claims description 2
- QIERDZRKNWKONI-CUVJYRNJSA-N ethyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1F)C1=NOCC1OCC QIERDZRKNWKONI-CUVJYRNJSA-N 0.000 claims description 2
- RHEGMEPBTMOUDW-BHWOMJMDSA-N ethyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclopropylpropanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)CC2CC2)C=C1)C1=NOCC1OCC RHEGMEPBTMOUDW-BHWOMJMDSA-N 0.000 claims description 2
- RCZKCMOUOWWRFG-LWKPJOBUSA-N ethyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-methylbutanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C(C)C)C=C1)C1=NOCC1OCC RCZKCMOUOWWRFG-LWKPJOBUSA-N 0.000 claims description 2
- LIJQVSXCBCKMIA-CFMCSPIPSA-N ethyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]butanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)CC)C=C1)C1=NOCC1OCC LIJQVSXCBCKMIA-CFMCSPIPSA-N 0.000 claims description 2
- YQCLDEIDBSPZMB-XLLULAGJSA-N ethyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OCC)C)C=C1)C1=NOCC1OCC YQCLDEIDBSPZMB-XLLULAGJSA-N 0.000 claims description 2
- 229940126181 ion channel inhibitor Drugs 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- SURXZLDCSHFGGG-MYHCZTBNSA-N methyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4,5-dichlorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C)C=C1Cl)C1=NOCC1OCCCC SURXZLDCSHFGGG-MYHCZTBNSA-N 0.000 claims description 2
- FOCDAAOGIXEKFU-MYHCZTBNSA-N methyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chloro-5-fluorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C)C=C1F)C1=NOCC1OCCCC FOCDAAOGIXEKFU-MYHCZTBNSA-N 0.000 claims description 2
- ZEDCGCAELHTFHT-ZENAZSQFSA-N methyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]-3-cyclopropylpropanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)CC2CC2)C=C1)C1=NOCC1OCCCC ZEDCGCAELHTFHT-ZENAZSQFSA-N 0.000 claims description 2
- FBRZRJHSFMWHER-LBAUFKAWSA-N methyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]butanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)CC)C=C1)C1=NOCC1OCCCC FBRZRJHSFMWHER-LBAUFKAWSA-N 0.000 claims description 2
- LQMODWFATWIWHJ-VPHXOMNUSA-N methyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOCC1OCCCC LQMODWFATWIWHJ-VPHXOMNUSA-N 0.000 claims description 2
- BQHNYXQYOITHKI-VPHXOMNUSA-N methyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-fluorophenoxy]propanoate Chemical compound FC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOCC1OCCCC BQHNYXQYOITHKI-VPHXOMNUSA-N 0.000 claims description 2
- JWEQFVWMPBNARP-LLTODGECSA-N methyl (2S)-2-[2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-fluorophenoxy]propanoate Chemical compound FC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOCC1OCC JWEQFVWMPBNARP-LLTODGECSA-N 0.000 claims description 2
- YLZMMDQUXGWMOV-OADYLZGLSA-N methyl (2S)-2-[4,5-dichloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C)C=C1Cl)C1=NOCC1OCC YLZMMDQUXGWMOV-OADYLZGLSA-N 0.000 claims description 2
- BXQKTERQFAQKOB-DAFXYXGESA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]-2-cyclopropylacetate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C2CC2)C=C1F)C1=NOCC1OCCCC BXQKTERQFAQKOB-DAFXYXGESA-N 0.000 claims description 2
- VNQXIPLWBYEILD-MYHCZTBNSA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C)C=C1F)C1=NOCC1OCCCC VNQXIPLWBYEILD-MYHCZTBNSA-N 0.000 claims description 2
- MXXQYYWVNGCEAL-OYKVQYDMSA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclobutylpropanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)CC2CCC2)C=C1)C1=NOCC1OCCCC MXXQYYWVNGCEAL-OYKVQYDMSA-N 0.000 claims description 2
- QOHOHZFDEFLSRM-ZENAZSQFSA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclopropylpropanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)CC2CC2)C=C1)C1=NOCC1OCCCC QOHOHZFDEFLSRM-ZENAZSQFSA-N 0.000 claims description 2
- UUTONXXWXRCDMN-DAFXYXGESA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-methylbutanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C(C)C)C=C1)C1=NOCC1OCCCC UUTONXXWXRCDMN-DAFXYXGESA-N 0.000 claims description 2
- ZAETWIKEZCRKQV-LBAUFKAWSA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]butanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)CC)C=C1)C1=NOCC1OCCCC ZAETWIKEZCRKQV-LBAUFKAWSA-N 0.000 claims description 2
- ZKQJBFXHYINFMD-WMCAAGNKSA-N methyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]-2-cyclopropylacetate Chemical compound CCOC1C(C(C=C(C(F)=C2)Br)=C2O[C@@H](C2CC2)C(OC)=O)=NOC1 ZKQJBFXHYINFMD-WMCAAGNKSA-N 0.000 claims description 2
- XYSSZORHCIQLPL-OADYLZGLSA-N methyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C)C=C1F)C1=NOCC1OCC XYSSZORHCIQLPL-OADYLZGLSA-N 0.000 claims description 2
- NCOJTCXTAJACAD-BHWOMJMDSA-N methyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclobutylpropanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)CC2CCC2)C=C1)C1=NOCC1OCC NCOJTCXTAJACAD-BHWOMJMDSA-N 0.000 claims description 2
- RQDWNRFUEOIFSN-VYRBHSGPSA-N methyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclopropylpropanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)CC2CC2)C=C1)C1=NOCC1OCC RQDWNRFUEOIFSN-VYRBHSGPSA-N 0.000 claims description 2
- OVATUOPKSFCFJB-NBFOIZRFSA-N methyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]butanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)CC)C=C1)C1=NOCC1OCC OVATUOPKSFCFJB-NBFOIZRFSA-N 0.000 claims description 2
- JJKUILZIJHTKIE-OADYLZGLSA-N methyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)-5-fluorophenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C)C=C1F)C1=NOCC1OCC JJKUILZIJHTKIE-OADYLZGLSA-N 0.000 claims description 2
- KJUZJEGYAZVKQS-NBFOIZRFSA-N methyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]butanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)CC)C=C1)C1=NOCC1OCC KJUZJEGYAZVKQS-NBFOIZRFSA-N 0.000 claims description 2
- DOHRVPYYGXLFDS-LLTODGECSA-N methyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOCC1OCC DOHRVPYYGXLFDS-LLTODGECSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910052722 tritium Inorganic materials 0.000 claims description 2
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims 4
- WTXDLLPQPOWKKY-UHFFFAOYSA-N BrC1=CC(=C(OCC(=O)OC)C=C1)C1=NOCC1OCC Chemical compound BrC1=CC(=C(OCC(=O)OC)C=C1)C1=NOCC1OCC WTXDLLPQPOWKKY-UHFFFAOYSA-N 0.000 claims 1
- DBHZAQFYUJZJHD-XLLULAGJSA-N CCCCOC1CON=C1C2=C(C=CC(=C2)Br)O[C@@H](C)C(=O)O Chemical compound CCCCOC1CON=C1C2=C(C=CC(=C2)Br)O[C@@H](C)C(=O)O DBHZAQFYUJZJHD-XLLULAGJSA-N 0.000 claims 1
- 241001328813 Methles Species 0.000 claims 1
- IOFINMLEPBCHLM-DAFXYXGESA-N methyl (2S)-2-[2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)-4-chlorophenoxy]-3-methylbutanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C(C)C)C=C1)C1=NOCC1OCCCC IOFINMLEPBCHLM-DAFXYXGESA-N 0.000 claims 1
- YMOVIQILYRAENR-JKGQDXBKSA-N methyl (2S)-2-[4-bromo-2-(4-butoxy-5-methyl-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C)C=C1)C1=NOC(C1OCCCC)C YMOVIQILYRAENR-JKGQDXBKSA-N 0.000 claims 1
- MLRZYNJXINQOJZ-WMCAAGNKSA-N methyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-methylbutanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC)C(C)C)C=C1)C1=NOCC1OCC MLRZYNJXINQOJZ-WMCAAGNKSA-N 0.000 claims 1
- KOAUHFABBSBWCR-VYRBHSGPSA-N methyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclopropylpropanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)CC2CC2)C=C1)C1=NOCC1OCC KOAUHFABBSBWCR-VYRBHSGPSA-N 0.000 claims 1
- FWTXGDXAPSFAAQ-WMCAAGNKSA-N methyl (2S)-2-[4-chloro-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-methylbutanoate Chemical compound ClC1=CC(=C(O[C@H](C(=O)OC)C(C)C)C=C1)C1=NOCC1OCC FWTXGDXAPSFAAQ-WMCAAGNKSA-N 0.000 claims 1
- VVQUXXLBQJNMMM-XJDOXCRVSA-N tert-butyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-cyclopropylpropanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC(C)(C)C)CC2CC2)C=C1)C1=NOCC1OCCCC VVQUXXLBQJNMMM-XJDOXCRVSA-N 0.000 claims 1
- HCWSOOWJKJJYIC-CWQZNGJJSA-N tert-butyl (2S)-2-[4-bromo-2-(4-butoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC(C)(C)C)C)C=C1)C1=NOCC1OCCCC HCWSOOWJKJJYIC-CWQZNGJJSA-N 0.000 claims 1
- JQBDKFUSZCYWPZ-YJPTXTSQSA-N tert-butyl (2S)-2-[4-bromo-2-(4-butoxy-5-cyclopropyl-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC(C)(C)C)C)C=C1)C1=NOC(C1OCCCC)C1CC1 JQBDKFUSZCYWPZ-YJPTXTSQSA-N 0.000 claims 1
- QKNUVKUJGYCDNR-DAFXYXGESA-N tert-butyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]-3-methylbutanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC(C)(C)C)C(C)C)C=C1)C1=NOCC1OCC QKNUVKUJGYCDNR-DAFXYXGESA-N 0.000 claims 1
- CKEXYNZRZIVRCD-LBAUFKAWSA-N tert-butyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]butanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC(C)(C)C)CC)C=C1)C1=NOCC1OCC CKEXYNZRZIVRCD-LBAUFKAWSA-N 0.000 claims 1
- OKOVBKBUFUIKQE-VPHXOMNUSA-N tert-butyl (2S)-2-[4-bromo-2-(4-ethoxy-4,5-dihydro-1,2-oxazol-3-yl)phenoxy]propanoate Chemical compound BrC1=CC(=C(O[C@H](C(=O)OC(C)(C)C)C)C=C1)C1=NOCC1OCC OKOVBKBUFUIKQE-VPHXOMNUSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| EP19181262 | 2019-06-19 | ||
| PCT/EP2020/067065 WO2020254554A1 (en) | 2019-06-19 | 2020-06-19 | Process for the preparation of clc-1 chloride channel inhibitors |
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| EP (1) | EP3986878B1 (https=) |
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| CA (1) | CA3137672A1 (https=) |
| ES (1) | ES3000437T3 (https=) |
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| TW (1) | TWI849152B (https=) |
| WO (1) | WO2020254554A1 (https=) |
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| WO2024180199A1 (en) | 2023-03-02 | 2024-09-06 | Nmd Pharma A/S | Compositions and methods for treating charcot–marie–tooth disease |
| JP2026508357A (ja) | 2023-03-02 | 2026-03-10 | エヌエムディー ファーマ エー／エス | 脊髄性筋萎縮症を処置するための組成物及び方法 |
| EP4731200A1 (en) | 2023-06-20 | 2026-04-29 | NMD Pharma A/S | Clc-1 inhibitors for use in the treatment of multiple sclerosis and neuromuscular diseases |
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| WO2009097970A1 (de) * | 2008-02-05 | 2009-08-13 | Sanofi-Aventis | Triazolopyridazine als par1-inhibitoren, ihre herstellung und verwendung als arzneimittel |
| JP2015505560A (ja) * | 2012-02-03 | 2015-02-23 | ゾエティス・エルエルシー | 抗寄生虫薬としてのキラルイソオキサゾリンアゼチジン誘導体の製造法 |
| MX389242B (es) | 2015-06-15 | 2025-03-20 | Nmd Pharma As | Compuestos para su uso en el tratamiento de trastornos neuromusculares |
| US10385028B2 (en) * | 2017-12-14 | 2019-08-20 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| TWI780281B (zh) | 2017-12-14 | 2022-10-11 | 丹麥商Ｎｍｄ藥品公司 | 用於治療神經肌肉病症的化合物 |
-
2020
- 2020-06-19 BR BR112021025588A patent/BR112021025588A2/pt unknown
- 2020-06-19 IL IL287901A patent/IL287901B2/en unknown
- 2020-06-19 ES ES20734157T patent/ES3000437T3/es active Active
- 2020-06-19 SG SG11202111122RA patent/SG11202111122RA/en unknown
- 2020-06-19 EP EP20734157.9A patent/EP3986878B1/en active Active
- 2020-06-19 CN CN202080043796.2A patent/CN113993852B/zh active Active
- 2020-06-19 HU HUE20734157A patent/HUE069104T2/hu unknown
- 2020-06-19 TW TW109120910A patent/TWI849152B/zh active
- 2020-06-19 US US17/619,312 patent/US12221425B2/en active Active
- 2020-06-19 JP JP2021569300A patent/JP7595945B2/ja active Active
- 2020-06-19 MX MX2021013507A patent/MX2021013507A/es unknown
- 2020-06-19 CA CA3137672A patent/CA3137672A1/en active Pending
- 2020-06-19 AR ARP200101735A patent/AR119198A1/es unknown
- 2020-06-19 AU AU2020298092A patent/AU2020298092B2/en active Active
- 2020-06-19 KR KR1020217037880A patent/KR102900834B1/ko active Active
- 2020-06-19 WO PCT/EP2020/067065 patent/WO2020254554A1/en not_active Ceased
- 2020-06-19 PL PL20734157.9T patent/PL3986878T3/pl unknown
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2021
- 2021-10-11 ZA ZA2021/07653A patent/ZA202107653B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP3986878A1 (en) | 2022-04-27 |
| HUE069104T2 (hu) | 2025-02-28 |
| BR112021025588A2 (pt) | 2022-02-01 |
| IL287901A (en) | 2022-01-01 |
| PL3986878T3 (pl) | 2025-01-20 |
| EP3986878C0 (en) | 2024-09-25 |
| CN113993852A (zh) | 2022-01-28 |
| TWI849152B (zh) | 2024-07-21 |
| US12221425B2 (en) | 2025-02-11 |
| KR102900834B1 (ko) | 2025-12-16 |
| AU2020298092A1 (en) | 2021-11-18 |
| CN113993852B (zh) | 2024-12-17 |
| SG11202111122RA (en) | 2021-11-29 |
| MX2021013507A (es) | 2021-12-10 |
| TW202115003A (zh) | 2021-04-16 |
| AU2020298092A8 (en) | 2025-04-24 |
| IL287901B2 (en) | 2025-02-01 |
| CA3137672A1 (en) | 2020-12-24 |
| WO2020254554A1 (en) | 2020-12-24 |
| JP2022537493A (ja) | 2022-08-26 |
| JP7595945B2 (ja) | 2024-12-09 |
| IL287901B1 (en) | 2024-10-01 |
| AU2020298092B2 (en) | 2025-09-25 |
| ZA202107653B (en) | 2023-05-31 |
| EP3986878B1 (en) | 2024-09-25 |
| KR20220022895A (ko) | 2022-02-28 |
| AR119198A1 (es) | 2021-12-01 |
| US20220298124A1 (en) | 2022-09-22 |
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