AU2008273923B2 - Amino acid derivatives - Google Patents
Amino acid derivatives Download PDFInfo
- Publication number
- AU2008273923B2 AU2008273923B2 AU2008273923A AU2008273923A AU2008273923B2 AU 2008273923 B2 AU2008273923 B2 AU 2008273923B2 AU 2008273923 A AU2008273923 A AU 2008273923A AU 2008273923 A AU2008273923 A AU 2008273923A AU 2008273923 B2 AU2008273923 B2 AU 2008273923B2
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- phenyl
- compound
- group
- 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.)
- Ceased
Links
- 150000003862 amino acid derivatives Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- 230000003291 dopaminomimetic effect Effects 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 44
- -1 cyano, hydroxy, mercapto Chemical class 0.000 claims description 43
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 24
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 23
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000006413 ring segment Chemical group 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 208000018737 Parkinson disease Diseases 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
- 125000005248 alkyl aryloxy group Chemical group 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 125000004185 ester group Chemical group 0.000 claims description 8
- 230000011664 signaling Effects 0.000 claims description 8
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 7
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 208000012661 Dyskinesia Diseases 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 230000006735 deficit Effects 0.000 claims description 6
- 230000001771 impaired effect Effects 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 235000001014 amino acid Nutrition 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 229960004502 levodopa Drugs 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- 230000000737 periodic effect Effects 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 208000019505 Deglutition disease Diseases 0.000 claims description 2
- 208000014094 Dystonic disease Diseases 0.000 claims description 2
- 201000005625 Neuroleptic malignant syndrome Diseases 0.000 claims description 2
- 206010035104 Pituitary tumour Diseases 0.000 claims description 2
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 2
- 208000016620 Tourette disease Diseases 0.000 claims description 2
- 208000010118 dystonia Diseases 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- MSIJLVMSKDXAQN-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]-4-methylpiperazine;hydron;chloride Chemical compound Cl.C1CN(C)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 MSIJLVMSKDXAQN-UHFFFAOYSA-N 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 150000002994 phenylalanines Chemical class 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 39
- 238000004128 high performance liquid chromatography Methods 0.000 description 36
- 239000000243 solution Substances 0.000 description 26
- 230000014759 maintenance of location Effects 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 21
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
- 229940093499 ethyl acetate Drugs 0.000 description 15
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 229960003638 dopamine Drugs 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 125000002757 morpholinyl group Chemical group 0.000 description 7
- 125000004193 piperazinyl group Chemical group 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 238000001665 trituration Methods 0.000 description 7
- 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 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 6
- 229940073608 benzyl chloride Drugs 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 125000003386 piperidinyl group Chemical group 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000003954 decarboxylase inhibitor Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 230000006742 locomotor activity Effects 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 229910014455 Ca-Cb Inorganic materials 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 description 4
- 125000002541 furyl group Chemical group 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- MBQTYGBICLNQKP-INIZCTEOSA-N (2s)-3-(3-hydroxy-4-phenylmethoxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC1=CC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CC=C1OCC1=CC=CC=C1 MBQTYGBICLNQKP-INIZCTEOSA-N 0.000 description 3
- RLLZUOMFFRLUIF-MHZLTWQESA-N (2s)-3-[3,4-bis(phenylmethoxy)phenyl]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 RLLZUOMFFRLUIF-MHZLTWQESA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XMNGSPOWUCNRMO-UHFFFAOYSA-N N-succinimidyl N-methylcarbamate Chemical compound CNC(=O)ON1C(=O)CCC1=O XMNGSPOWUCNRMO-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- HZMHQSVPGNFQKB-RSAXXLAASA-N [(2s)-1-methoxy-3-[3-(methylcarbamoyloxy)-4-phenylmethoxyphenyl]-1-oxopropan-2-yl]azanium;chloride Chemical compound [Cl-].CNC(=O)OC1=CC(C[C@H]([NH3+])C(=O)OC)=CC=C1OCC1=CC=CC=C1 HZMHQSVPGNFQKB-RSAXXLAASA-N 0.000 description 3
- FEVRYGIZBUZMFL-RSAXXLAASA-N [(2s)-1-methoxy-3-[4-(methylcarbamoyloxy)-3-phenylmethoxyphenyl]-1-oxopropan-2-yl]azanium;chloride Chemical compound [Cl-].CNC(=O)OC1=CC=C(C[C@H]([NH3+])C(=O)OC)C=C1OCC1=CC=CC=C1 FEVRYGIZBUZMFL-RSAXXLAASA-N 0.000 description 3
- VVVGWIIODQUFJT-IODNYQNNSA-N [(2s)-3-(3,4-dihydroxyphenyl)-1-[[(2s)-3-[3-hydroxy-4-(methylcarbamoyloxy)phenyl]-1-methoxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]azanium;chloride Chemical compound [Cl-].C1=C(O)C(OC(=O)NC)=CC=C1C[C@@H](C(=O)OC)NC(=O)[C@@H]([NH3+])CC1=CC=C(O)C(O)=C1 VVVGWIIODQUFJT-IODNYQNNSA-N 0.000 description 3
- JPBSBSABMIARQQ-MERQFXBCSA-N [(2s)-3-[3-(ethylcarbamoyloxy)-4-hydroxyphenyl]-1-[(1-methoxy-2-methyl-1-oxopropan-2-yl)amino]-1-oxopropan-2-yl]azanium;chloride Chemical compound [Cl-].CCNC(=O)OC1=CC(C[C@H]([NH3+])C(=O)NC(C)(C)C(=O)OC)=CC=C1O JPBSBSABMIARQQ-MERQFXBCSA-N 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical compound OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 description 3
- 229960000911 benserazide Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 description 3
- 235000013681 dietary sucrose Nutrition 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- LBFUDVHXFCKTDJ-COCZKOEFSA-N methyl (2s)-2-[[(2s)-3-[3,4-bis(phenylmethoxy)phenyl]-2-(phenylmethoxycarbonylamino)propanoyl]amino]-3-[4-(methylcarbamoyloxy)-3-phenylmethoxyphenyl]propanoate Chemical compound C([C@@H](C(=O)N[C@@H](CC1=CC=C(C(=C1)OCC=1C=CC=CC=1)OC(=O)NC)C(=O)OC)NC(=O)OCC=1C=CC=CC=1)C(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 LBFUDVHXFCKTDJ-COCZKOEFSA-N 0.000 description 3
- XRUVERDUHRJKJQ-NRFANRHFSA-N methyl (2s)-3-(3-hydroxy-4-phenylmethoxyphenyl)-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)OCC=1C=CC=CC=1)C(C=C1O)=CC=C1OCC1=CC=CC=C1 XRUVERDUHRJKJQ-NRFANRHFSA-N 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/42—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/44—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C307/02—Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/25—Sulfonic acids having sulfo groups bound to carbon atoms of rings other than six-membered aromatic rings of a carbon skeleton
-
- 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
- C07D295/16—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 acylated on ring nitrogen atoms
- C07D295/20—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 acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/0606—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Psychology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Anesthesiology (AREA)
- 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)
- Pyrrole Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0713189.9 | 2007-07-06 | ||
| GBGB0713189.9A GB0713189D0 (en) | 2007-07-06 | 2007-07-06 | Amino acid derivatives |
| PCT/GB2008/002313 WO2009007696A1 (en) | 2007-07-06 | 2008-07-04 | Amino acid derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2008273923A1 AU2008273923A1 (en) | 2009-01-15 |
| AU2008273923B2 true AU2008273923B2 (en) | 2013-07-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2008273923A Ceased AU2008273923B2 (en) | 2007-07-06 | 2008-07-04 | Amino acid derivatives |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8258097B2 (enExample) |
| EP (1) | EP2176217B1 (enExample) |
| JP (1) | JP5422557B2 (enExample) |
| CN (1) | CN101730678B (enExample) |
| AU (1) | AU2008273923B2 (enExample) |
| BR (1) | BRPI0814800A2 (enExample) |
| CA (1) | CA2692608A1 (enExample) |
| GB (1) | GB0713189D0 (enExample) |
| MX (1) | MX2010000150A (enExample) |
| NZ (1) | NZ583075A (enExample) |
| WO (1) | WO2009007696A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6567049B2 (ja) | 2014-10-21 | 2019-08-28 | アッヴィ・インコーポレイテッド | カルビドパおよびｌ−ドーパプロドラッグならびにそれらの使用方法 |
| AU2016258179B2 (en) | 2015-05-06 | 2021-07-01 | Synagile Corporation | Pharmaceutical suspensions containing drug particles, devices for their administration, and methods of their use |
| AU2016314617A1 (en) * | 2015-09-02 | 2018-04-26 | Cellix Bio Private Limited | Compositions and methods for the treatment of parkinson's disease |
| EP3749677A1 (en) | 2018-02-08 | 2020-12-16 | Yissum Research Development Company of the Hebrew University of Jerusalem Ltd | Dopamine precursors |
| CA3117983A1 (en) | 2018-11-15 | 2020-05-22 | Abbvie Inc. | Pharmaceutical formulations for subcutaneous administration |
| BR112022003974A2 (pt) * | 2019-09-05 | 2022-05-24 | Neuroderm Ltd | Composições líquidas que compreendem um conjugado de aminoácido de levodopa e seus usos |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5013753A (en) * | 1988-07-29 | 1991-05-07 | Simes | Prodrugs of dopamine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH562199A5 (enExample) * | 1970-10-30 | 1975-05-30 | Hoffmann La Roche | |
| JPS5422337A (en) | 1977-07-18 | 1979-02-20 | Kyowa Hakko Kogyo Co Ltd | Alphamethyldopa derivatives |
-
2007
- 2007-07-06 GB GBGB0713189.9A patent/GB0713189D0/en not_active Ceased
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2008
- 2008-07-04 WO PCT/GB2008/002313 patent/WO2009007696A1/en not_active Ceased
- 2008-07-04 US US12/667,917 patent/US8258097B2/en not_active Expired - Fee Related
- 2008-07-04 NZ NZ583075A patent/NZ583075A/en not_active IP Right Cessation
- 2008-07-04 EP EP08775861A patent/EP2176217B1/en not_active Not-in-force
- 2008-07-04 AU AU2008273923A patent/AU2008273923B2/en not_active Ceased
- 2008-07-04 CN CN200880023320.1A patent/CN101730678B/zh not_active Expired - Fee Related
- 2008-07-04 CA CA 2692608 patent/CA2692608A1/en not_active Abandoned
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- 2008-07-04 BR BRPI0814800-7A2A patent/BRPI0814800A2/pt not_active IP Right Cessation
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5013753A (en) * | 1988-07-29 | 1991-05-07 | Simes | Prodrugs of dopamine |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009007696A1 (en) | 2009-01-15 |
| US8258097B2 (en) | 2012-09-04 |
| BRPI0814800A2 (pt) | 2015-02-03 |
| MX2010000150A (es) | 2010-03-18 |
| EP2176217B1 (en) | 2012-08-22 |
| US20100190725A1 (en) | 2010-07-29 |
| CN101730678B (zh) | 2014-04-02 |
| AU2008273923A1 (en) | 2009-01-15 |
| NZ583075A (en) | 2011-08-26 |
| CN101730678A (zh) | 2010-06-09 |
| EP2176217A1 (en) | 2010-04-21 |
| GB0713189D0 (en) | 2007-08-15 |
| JP2010532751A (ja) | 2010-10-14 |
| CA2692608A1 (en) | 2009-01-15 |
| JP5422557B2 (ja) | 2014-02-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |