JP5422557B2 - アミノ酸誘導体 - Google Patents
アミノ酸誘導体 Download PDFInfo
- Publication number
- JP5422557B2 JP5422557B2 JP2010514127A JP2010514127A JP5422557B2 JP 5422557 B2 JP5422557 B2 JP 5422557B2 JP 2010514127 A JP2010514127 A JP 2010514127A JP 2010514127 A JP2010514127 A JP 2010514127A JP 5422557 B2 JP5422557 B2 JP 5422557B2
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- JP
- Japan
- Prior art keywords
- compound according
- group
- phenyl
- hydrogen
- alkyl
- 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.)
- Expired - Fee Related
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- 150000003862 amino acid derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 97
- -1 carboxy, carboxy ester Chemical class 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
- 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 22
- 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 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 208000018737 Parkinson disease Diseases 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000006413 ring segment Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 230000003291 dopaminomimetic effect Effects 0.000 claims description 7
- 125000004185 ester group Chemical group 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000033001 locomotion 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
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 4
- 235000001014 amino acid Nutrition 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 230000001771 impaired effect Effects 0.000 claims description 4
- 125000001620 monocyclic carbocycle group Chemical group 0.000 claims description 4
- 230000011664 signaling Effects 0.000 claims description 4
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 3
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 3
- 229960004502 levodopa Drugs 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
- 208000019505 Deglutition disease Diseases 0.000 claims description 2
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 2
- 201000005625 Neuroleptic malignant syndrome Diseases 0.000 claims description 2
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims description 2
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 2
- 208000016620 Tourette disease Diseases 0.000 claims description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 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
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 230000000737 periodic effect Effects 0.000 claims description 2
- 208000010916 pituitary tumor Diseases 0.000 claims description 2
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 230000005748 tumor development Effects 0.000 claims description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
- 206010003591 Ataxia Diseases 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 238000000034 method Methods 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 38
- 238000004128 high performance liquid chromatography Methods 0.000 description 37
- 239000000203 mixture Substances 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 230000014759 maintenance of location Effects 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 22
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 20
- 230000008569 process Effects 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 17
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-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
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 229960003638 dopamine Drugs 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 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
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 125000001072 heteroaryl group Chemical group 0.000 description 7
- 208000024891 symptom Diseases 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 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
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
- 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
- 239000012267 brine Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
- 208000016285 Movement disease Diseases 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 239000003954 decarboxylase inhibitor Substances 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 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
- 239000000463 material Substances 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate 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
- 238000001665 trituration Methods 0.000 description 4
- 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
- YWSGEUPAPWEURU-MOGJOVFKSA-N [(2s)-1-[[(2s)-3-[4-acetyloxy-3-(methylcarbamoyloxy)phenyl]-1-methoxy-1-oxopropan-2-yl]amino]-3-(3,4-dihydroxyphenyl)-1-oxopropan-2-yl]azanium;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=C(OC(C)=O)C(OC(=O)NC)=CC(C[C@H](NC(=O)[C@@H]([NH3+])CC=2C=C(O)C(O)=CC=2)C(=O)OC)=C1 YWSGEUPAPWEURU-MOGJOVFKSA-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
- 239000002253 acid Substances 0.000 description 3
- 125000000217 alkyl 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
- 239000002775 capsule Substances 0.000 description 3
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- RQDURAVAVCOIEU-COCZKOEFSA-N methyl (2s)-2-[[(2s)-3-[3,4-bis(phenylmethoxy)phenyl]-2-(phenylmethoxycarbonylamino)propanoyl]amino]-3-[3-(methylcarbamoyloxy)-4-phenylmethoxyphenyl]propanoate Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C=C(C(=CC=1)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 RQDURAVAVCOIEU-COCZKOEFSA-N 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
- LEELHJVODAFSDL-NRFANRHFSA-N methyl 2-[[(2s)-3-[3-(ethylcarbamoyloxy)-4-phenylmethoxyphenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-2-methylpropanoate Chemical compound CCNC(=O)OC1=CC(C[C@H](NC(=O)OC(C)(C)C)C(=O)NC(C)(C)C(=O)OC)=CC=C1OCC1=CC=CC=C1 LEELHJVODAFSDL-NRFANRHFSA-N 0.000 description 3
- 125000002971 oxazolyl group Chemical group 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- 238000003908 quality control method Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
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Classifications
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
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- 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
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- 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
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- 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
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
- Peptides Or Proteins (AREA)
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| PCT/GB2008/002313 WO2009007696A1 (en) | 2007-07-06 | 2008-07-04 | Amino acid derivatives |
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| 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 |
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|---|---|---|---|---|
| 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 |
| IT1226727B (it) * | 1988-07-29 | 1991-02-05 | Simes | Farmaci precursori della dopamina. |
-
2007
- 2007-07-06 GB GBGB0713189.9A patent/GB0713189D0/en not_active Ceased
-
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
- 2008-07-04 MX MX2010000150A patent/MX2010000150A/es active IP Right Grant
- 2008-07-04 BR BRPI0814800-7A2A patent/BRPI0814800A2/pt not_active IP Right Cessation
- 2008-07-04 JP JP2010514127A patent/JP5422557B2/ja not_active Expired - Fee Related
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 |
| AU2008273923B2 (en) | 2013-07-11 |
| 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 |
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