BR112020007744A2 - derivados azabiciclo e diazepina para o tratamento de distúrbios oculares - Google Patents
derivados azabiciclo e diazepina para o tratamento de distúrbios oculares Download PDFInfo
- Publication number
- BR112020007744A2 BR112020007744A2 BR112020007744-5A BR112020007744A BR112020007744A2 BR 112020007744 A2 BR112020007744 A2 BR 112020007744A2 BR 112020007744 A BR112020007744 A BR 112020007744A BR 112020007744 A2 BR112020007744 A2 BR 112020007744A2
- Authority
- BR
- Brazil
- Prior art keywords
- mmol
- methyl
- compound
- octan
- azabicyclo
- Prior art date
Links
- 208000030533 eye disease Diseases 0.000 title claims abstract description 8
- 238000011282 treatment Methods 0.000 title abstract description 16
- 125000002576 diazepinyl group Chemical class N1N=C(C=CC=C1)* 0.000 title abstract description 3
- 239000000203 mixture Substances 0.000 claims abstract description 90
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
- 150000001875 compounds Chemical class 0.000 claims description 167
- 150000003839 salts Chemical class 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000001188 haloalkyl group Chemical group 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 150000002825 nitriles Chemical class 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 8
- GOPDFXUMARJJEA-UHFFFAOYSA-N amino(nitro)azanide Chemical compound N[N-][N+]([O-])=O GOPDFXUMARJJEA-UHFFFAOYSA-N 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 150000003457 sulfones Chemical class 0.000 claims description 8
- 150000003462 sulfoxides Chemical class 0.000 claims description 8
- 230000000699 topical effect Effects 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Chemical group 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 229910052805 deuterium Inorganic materials 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 229940124530 sulfonamide Drugs 0.000 claims description 4
- 150000003456 sulfonamides Chemical class 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 3
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 abstract description 9
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 173
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
- -1 octan-3-yl Chemical group 0.000 description 127
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 126
- 239000011541 reaction mixture Substances 0.000 description 113
- 239000000243 solution Substances 0.000 description 108
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 90
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 85
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
- 235000019439 ethyl acetate Nutrition 0.000 description 81
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 79
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 66
- 238000005160 1H NMR spectroscopy Methods 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 58
- 239000012267 brine Substances 0.000 description 57
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 57
- 239000007787 solid Substances 0.000 description 55
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- 239000003921 oil Substances 0.000 description 41
- 235000019198 oils Nutrition 0.000 description 41
- 239000000377 silicon dioxide Substances 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 33
- 235000019341 magnesium sulphate Nutrition 0.000 description 33
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 30
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 27
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
- 239000007832 Na2SO4 Substances 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 26
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 26
- 229910052938 sodium sulfate Inorganic materials 0.000 description 26
- 235000011152 sodium sulphate Nutrition 0.000 description 26
- 229930040373 Paraformaldehyde Natural products 0.000 description 25
- 229920002866 paraformaldehyde Polymers 0.000 description 25
- 238000000746 purification Methods 0.000 description 25
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 24
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 24
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 23
- 239000000047 product Substances 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 18
- 238000009472 formulation Methods 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000012223 aqueous fraction Substances 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 15
- XMLNCADGRIEXPK-KUMOIWDRSA-M chembl2146143 Chemical compound [Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N+]2(C)C)C(=O)C(CO)C1=CC=CC=C1 XMLNCADGRIEXPK-KUMOIWDRSA-M 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 13
- 229910052786 argon Inorganic materials 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 11
- 229930003347 Atropine Natural products 0.000 description 10
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 10
- 229960000396 atropine Drugs 0.000 description 10
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 235000019253 formic acid Nutrition 0.000 description 9
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- WWJHRSCUAQPFQO-UHFFFAOYSA-M 4-DAMP methiodide Chemical compound [I-].C1C[N+](C)(C)CCC1OC(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 WWJHRSCUAQPFQO-UHFFFAOYSA-M 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
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- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 6
- ATPPNMLQNZHDOG-UHFFFAOYSA-N 2-fluoro-2-phenylacetic acid Chemical compound OC(=O)C(F)C1=CC=CC=C1 ATPPNMLQNZHDOG-UHFFFAOYSA-N 0.000 description 5
- 241000937413 Axia Species 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
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- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 230000009871 nonspecific binding Effects 0.000 description 5
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- OEQJOYQHIGIVTN-UHFFFAOYSA-N tert-butyl nonanoate Chemical compound CCCCCCCCC(=O)OC(C)(C)C OEQJOYQHIGIVTN-UHFFFAOYSA-N 0.000 description 5
- IWEPXSFVSUOTLW-UHFFFAOYSA-N 2,3-dihydroxy-2-phenylpropanoic acid Chemical compound OCC(O)(C(O)=O)C1=CC=CC=C1 IWEPXSFVSUOTLW-UHFFFAOYSA-N 0.000 description 4
- GJXTXPRZKRDQLG-UHFFFAOYSA-N 2-(hydroxymethyl)-2-phenylbutanoic acid Chemical compound CCC(CO)(C(O)=O)C1=CC=CC=C1 GJXTXPRZKRDQLG-UHFFFAOYSA-N 0.000 description 4
- NCWBXNIIEXKLIB-UHFFFAOYSA-N 2-(hydroxymethyl)-3-(4-methoxyphenyl)-2-phenylpropanoic acid Chemical compound COC1=CC=C(C=C1)CC(CO)(C2=CC=CC=C2)C(=O)O NCWBXNIIEXKLIB-UHFFFAOYSA-N 0.000 description 4
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
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- 238000003556 assay Methods 0.000 description 4
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
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- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
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- 229910052708 sodium Inorganic materials 0.000 description 4
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- 238000006467 substitution reaction Methods 0.000 description 4
- CYHOMWAPJJPNMW-DHBOJHSNSA-N (1s,5r)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol Chemical compound C1C(O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-DHBOJHSNSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- PCRICPYPVZKEBZ-UHFFFAOYSA-N 2,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)CC1=CC=CC=C1 PCRICPYPVZKEBZ-UHFFFAOYSA-N 0.000 description 3
- UCKXXAPGEQHBOS-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-hydroxy-2-methylpropanoic acid Chemical compound OCC(C)(C(O)=O)C1=CC=C(Cl)C=C1 UCKXXAPGEQHBOS-UHFFFAOYSA-N 0.000 description 3
- HPHAXJQIKBBFHZ-UHFFFAOYSA-N 2-benzyl-3-hydroxy-2-phenylpropanoic acid Chemical compound C=1C=CC=CC=1C(CO)(C(O)=O)CC1=CC=CC=C1 HPHAXJQIKBBFHZ-UHFFFAOYSA-N 0.000 description 3
- VFWZIUUVUDYNJF-UHFFFAOYSA-N 2-fluoro-2-phenylacetyl chloride Chemical compound ClC(=O)C(F)C1=CC=CC=C1 VFWZIUUVUDYNJF-UHFFFAOYSA-N 0.000 description 3
- FOTITZRWZUAVPH-UHFFFAOYSA-N 2-phenylpropanoyl chloride Chemical compound ClC(=O)C(C)C1=CC=CC=C1 FOTITZRWZUAVPH-UHFFFAOYSA-N 0.000 description 3
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- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 3
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- RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical group C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 3
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- UGCFDZODATURDQ-UHFFFAOYSA-N methyl 2-(4-chlorophenyl)propanoate Chemical compound COC(=O)C(C)C1=CC=C(Cl)C=C1 UGCFDZODATURDQ-UHFFFAOYSA-N 0.000 description 1
- HAJSGGNCKPWNRY-UHFFFAOYSA-N methyl 2-fluoro-2-phenylpropanoate Chemical compound COC(=O)C(C)(F)C1=CC=CC=C1 HAJSGGNCKPWNRY-UHFFFAOYSA-N 0.000 description 1
- JHRORVVRXDUSKB-UHFFFAOYSA-N methyl 2-fluoro-3-hydroxy-2-phenylpropanoate Chemical compound COC(=O)C(F)(CO)C1=CC=CC=C1 JHRORVVRXDUSKB-UHFFFAOYSA-N 0.000 description 1
- NNUIBZHWOCEHFY-UHFFFAOYSA-N methyl 3-(3-chlorophenyl)-2-phenylpropanoate Chemical compound ClC=1C=C(C=CC=1)CC(C(=O)OC)C1=CC=CC=C1 NNUIBZHWOCEHFY-UHFFFAOYSA-N 0.000 description 1
- PAMJXAPZIAWDKT-UHFFFAOYSA-N methyl 3-(4-fluorophenyl)-2-phenylpropanoate Chemical compound C=1C=CC=CC=1C(C(=O)OC)CC1=CC=C(F)C=C1 PAMJXAPZIAWDKT-UHFFFAOYSA-N 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- JVNQOBDGCIZQTM-UHFFFAOYSA-N octan-3-yl 2,3-dihydroxy-2-phenylpropanoate Chemical compound OC(C(=O)OC(CC)CCCCC)(CO)C1=CC=CC=C1 JVNQOBDGCIZQTM-UHFFFAOYSA-N 0.000 description 1
- BBHSMYYIEJZHEP-UHFFFAOYSA-N octan-3-yl 2-benzyl-3-hydroxy-2-phenylpropanoate Chemical compound C(C1=CC=CC=C1)C(C(=O)OC(CC)CCCCC)(CO)C1=CC=CC=C1 BBHSMYYIEJZHEP-UHFFFAOYSA-N 0.000 description 1
- UULZSUCYCPUTIH-UHFFFAOYSA-N octan-3-yl 2-fluoro-3-hydroxy-2-phenylpropanoate Chemical compound CCCCCC(CC)OC(=O)C(CO)(C1=CC=CC=C1)F UULZSUCYCPUTIH-UHFFFAOYSA-N 0.000 description 1
- NTRDGYLOUSLMBW-UHFFFAOYSA-N octan-3-yl 3-fluoro-2-methyl-2-phenylpropanoate Chemical compound FCC(C(=O)OC(CC)CCCCC)(C1=CC=CC=C1)C NTRDGYLOUSLMBW-UHFFFAOYSA-N 0.000 description 1
- VQQQLADEEKZZQH-UHFFFAOYSA-N octan-3-yl 3-methoxy-2-methyl-2-phenylpropanoate hydrochloride Chemical compound Cl.COCC(C(=O)OC(CC)CCCCC)(C1=CC=CC=C1)C VQQQLADEEKZZQH-UHFFFAOYSA-N 0.000 description 1
- MMMZAOKWMPFGNO-UHFFFAOYSA-N octan-3-yl 4,4,4-trifluoro-2-phenylbutanoate Chemical compound FC(CC(C(=O)OC(CC)CCCCC)C1=CC=CC=C1)(F)F MMMZAOKWMPFGNO-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
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- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
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- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000006195 pent-4-inyl group Chemical group [H]C#CC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000010344 pupil dilation Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000012552 review Methods 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
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- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000010902 straw Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- SEGZJJSZYOEABC-UHFFFAOYSA-N tert-butyl 3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(O)CC2CCC1N2C(=O)OC(C)(C)C SEGZJJSZYOEABC-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
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- 230000000007 visual effect Effects 0.000 description 1
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- 239000003871 white petrolatum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical class CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/38—[b, e]- or [b, f]-condensed with six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762581073P | 2017-11-03 | 2017-11-03 | |
| US62/581,073 | 2017-11-03 | ||
| US201862749610P | 2018-10-23 | 2018-10-23 | |
| US62/749,610 | 2018-10-23 | ||
| PCT/IB2018/058631 WO2019087146A1 (en) | 2017-11-03 | 2018-11-02 | Azabicyclo and diazepine derivatives for treating ocular disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112020007744A2 true BR112020007744A2 (pt) | 2020-10-13 |
Family
ID=64267873
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112020007744-5A BR112020007744A2 (pt) | 2017-11-03 | 2018-11-02 | derivados azabiciclo e diazepina para o tratamento de distúrbios oculares |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US11306090B2 (https=) |
| EP (1) | EP3704117B1 (https=) |
| JP (3) | JP7065180B2 (https=) |
| KR (1) | KR20200083976A (https=) |
| CN (1) | CN111247147B (https=) |
| AU (3) | AU2018362010B2 (https=) |
| BR (1) | BR112020007744A2 (https=) |
| CA (2) | CA3205816A1 (https=) |
| MX (2) | MX2020004580A (https=) |
| SG (1) | SG11202002692XA (https=) |
| TW (2) | TWI826399B (https=) |
| WO (2) | WO2019087149A1 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7665519B2 (ja) * | 2019-02-01 | 2025-04-21 | アルコン インコーポレイティド | 近視を治療するための化合物、組成物及び医薬組成物 |
| US12527739B2 (en) | 2022-09-11 | 2026-01-20 | Alcon Inc. | Aqueous pharmaceutical compositions comprising benzyl atropine and uses thereof |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1165037B (de) | 1961-11-21 | 1964-03-12 | Dr. Schwarz Arzneimittelfabrik G.m.b.H., Monheim (RhId.) | Verfahren zur Herstellung von Estern quaternärer Atropiniumsalze. |
| GB994493A (en) | 1963-02-06 | 1965-06-10 | Lepetit Spa | Tropine derivative |
| DE1670177A1 (de) | 1966-12-28 | 1970-11-12 | Boehringer Sohn Ingelheim | Verfahren zur Herstellung von neuen N-substituierten Noratropiniumsalzen |
| US5223528A (en) | 1986-03-17 | 1993-06-29 | University Of Florida | Anticholinergic compounds, composititons and methods of treatment |
| IL158904A0 (en) | 2001-05-25 | 2004-05-12 | Valley Forge Pharmaceuticals | Pirenzepine ophthalmic gel |
| FR2834511B1 (fr) | 2002-01-07 | 2004-02-13 | Sanofi Synthelabo | Derives de 5-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, leur preparation et leur application en therapeutique |
| CN1546490A (zh) | 2003-12-15 | 2004-11-17 | 常俊标 | 不对称双羟基托品类生物碱及其合成新方法和药物用途 |
| CN1283639C (zh) | 2004-06-08 | 2006-11-08 | 吴建梅 | 治疗近视眼的哌仑西平有机酸盐及其滴眼剂 |
| US20070254914A1 (en) * | 2006-05-01 | 2007-11-01 | Non-Profit Organization Chang Gung Memorial Hospital | Low-concentration atropine solution for preventing myopia progression and preparing method thereof |
| PL2657234T3 (pl) | 2010-12-22 | 2017-06-30 | Meiji Seika Pharma Co., Ltd. | Optycznie czynna pochodna diazabicyklooktanowa i sposób jej wytwarzania |
-
2018
- 2018-11-02 CA CA3205816A patent/CA3205816A1/en active Pending
- 2018-11-02 MX MX2020004580A patent/MX2020004580A/es unknown
- 2018-11-02 US US16/760,192 patent/US11306090B2/en active Active
- 2018-11-02 KR KR1020207010292A patent/KR20200083976A/ko active Pending
- 2018-11-02 JP JP2020520577A patent/JP7065180B2/ja active Active
- 2018-11-02 BR BR112020007744-5A patent/BR112020007744A2/pt unknown
- 2018-11-02 TW TW107138927A patent/TWI826399B/zh active
- 2018-11-02 CN CN201880068606.5A patent/CN111247147B/zh active Active
- 2018-11-02 TW TW112150515A patent/TWI852865B/zh active
- 2018-11-02 CA CA3076457A patent/CA3076457C/en active Active
- 2018-11-02 WO PCT/IB2018/058637 patent/WO2019087149A1/en not_active Ceased
- 2018-11-02 EP EP18800336.2A patent/EP3704117B1/en active Active
- 2018-11-02 AU AU2018362010A patent/AU2018362010B2/en active Active
- 2018-11-02 WO PCT/IB2018/058631 patent/WO2019087146A1/en not_active Ceased
- 2018-11-02 SG SG11202002692XA patent/SG11202002692XA/en unknown
-
2020
- 2020-07-13 MX MX2022011310A patent/MX2022011310A/es unknown
-
2021
- 2021-07-16 AU AU2021205100A patent/AU2021205100B2/en active Active
-
2022
- 2022-03-21 US US17/699,606 patent/US11884666B2/en active Active
- 2022-04-25 JP JP2022071400A patent/JP2022101654A/ja active Pending
-
2023
- 2023-04-03 AU AU2023202036A patent/AU2023202036B2/en active Active
- 2023-11-30 US US18/524,807 patent/US12247028B2/en active Active
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2024
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