- Easy access to drug building-blocks through benzylic C-H functionalization of phenolic ethers by photoredox catalysis
-
A visible light-mediated photocatalyzed C-C-bond forming method for the benzylic C-H functionalization of phenolether containing synthetic building blocks based on a radical-cation/deprotonation strategy is reported. This method allows the mild, selective generation of benzyl radicals in phenolic complex molecules and drug-like compounds, providing new entries in synthetic and medicinal chemistry.
- Brandhofer, Tobias,Derdau, Volker,García Manche?o, Olga,Méndez, María,P?verlein, Christoph,Stinglhamer, Martin
-
supporting information
p. 6756 - 6759
(2021/07/13)
-
- Structural Transformative Antioxidants for Dual-Responsive Anti-Inflammatory Delivery and Photoacoustic Inflammation Imaging
-
We have synthesized a PEGylated, phenylboronic acid modified L-DOPA pro-antioxidant (pPAD) that can self-assemble into nanoparticles (pPADN) for the loading of a model glucocorticoid dexamethasone (Dex) through 1,3-diol/phenylboronic acid chemistry and hydrophobic interactions for more effective treatment of inflammation. Upon exposure to ROS, pPADN convert into the active form of L-DOPA, and a cascade of oxidative reactions transform it into antioxidative melanin-like materials. Concomitantly, the structural transformation of pPADN triggers the specific release of Dex, along with the acidic pH of inflammatory tissue. In a rat model of osteoarthritis, Dex-loaded pPADN markedly mitigate synovial inflammation, suppress joint destruction and cartilage matrix degradation, with negligible in vivo toxicity. Moreover, in situ structural transformation makes pPADN suitable for noninvasive monitoring of therapeutic effects as a photoacoustic imaging contrast agent.
- Zhao, Caiyan,Chen, Jingxiao,Ye, Jiamin,Li, Zhi,Su, Lichao,Wang, Junqing,Zhang, Ye,Chen, Jinghua,Yang, Huanghao,Shi, Jinjun,Song, Jibin
-
supporting information
p. 14458 - 14466
(2021/05/13)
-
- Small Molecule Inhibits Metal-Dependent and -Independent Multifaceted Toxicity of Alzheimer's Disease
-
Alzheimer's disease (AD) is one of the most devastating forms of dementia, without reliable treatments to cure, delay the onset, or prevent the disease progression. The proposed toxic mechanisms of AD include amyloidogenesis of amyloid β (Aβ), metal ion dyshomeostasis, redox active metal-Aβ inclusion complex formation, and generation of excessive reactive oxygen and nitrogen species (ROS and RNS). The imbalance in redox homeostasis causes oxidative stress, DNA damage, mitochondrial dysfunction, and inflammation, which collectively become a major hurdle in the development of effective therapeutic agents for multifactorial AD. This necessitates a multifunctional strategy to develop effective therapeutic agents to inhibit multifaceted toxicity. In this context, we report a rational design, synthesis, and detailed study to identify a small molecule multifunctional modulator (MFM) inspired by the human origin tripeptide. The lead, MFM 4, chelates and sequesters metal ions, disrupts their redox cycles, prevents excessive ROS production and oxidative stress, ameliorates oxidative DNA damage and mitochondrial dysfunction, and modulates Nrf2 protein signaling under oxidative stress conditions by eliminating the toxic stress elements. The MFM 4 was found to inhibit metal-dependent and -independent Aβ aggregation and qualified as a suitable candidate to inhibit Aβ-induced neuronal toxicity. The NMR spectroscopy study revealed molecular-level interactions of 4 with Aβ42, which explain the mechanism of aggregation inhibition. Furthermore, 4 effectively inhibited inflammation as revealed by reduction in nitric oxide (NO) production in LPS-activated glial cells. These key features make 4 a potential MFM platform to develop therapeutic agents for metal (Cu, Zn and Fe)-dependent and -independent multifaceted Aβ toxicity of AD.
- Samanta, Sourav,Rajasekhar, Kolla,Babagond, Vardhaman,Govindaraju, Thimmaiah
-
p. 3611 - 3621
(2019/09/10)
-
- Water-soluble L-DOPA esters
-
The present invention relates to novel compounds of the formula I, methods for their preparation and their use for treatment of diseases. The invention discloses the synthesis of levodopa (L-DOPA) esters by coupling polyhydroxy compounds or their derivatives to the L-DOPA carboxyl group. The synthesis allows to produce L-DOPA derivatives which are highly soluble in water as well as aqueous and biocompatible liquids and have an improved hydrolytic stability in water or aqueous and biocompatible media for an application over several days. The invention helps producing L-DOPA substances for applications in the fields of medicine, biology and medical engineering as well as in the pharmaceutical industry.
- -
-
Paragraph 0082
(2018/05/24)
-
- Base/Cryptand/Metal-Free Automated Nucleophilic Radiofluorination of [18F]FDOPA from Iodonium Salts: Importance of Hydrogen Carbonate Counterion
-
As evidenced by the number of publications and patents published in the last years, the radiosynthesis of 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine ([18F]FDOPA) using the nucleophilic [18F]F- process remains currently a challenge for the radiochemists scientific community even if promising methods for the radiofluorination of electron-rich aromatic structures were recently developed from arylboronate, arylstannane or iodonium salt precursors. In such context, based on the use of an iodonium triflate salt precursor, we optimized a fast and efficient radiofluorination route fully automated and free from any base, cryptand or metal catalyst for the radiosynthesis of [18F]FDOPA. Using this method, this clinically relevant radiotracer was produced in 64 min, 27–38 % RCY d.c. (n = 5), >99 % RCP, >99 % ee., and high Am 170–230 GBq/μmol. In addition, this optimization study clearly highlighted the important role of a triflate-hydrogen carbonate counterion exchange during the radiolabeling process to achieve high fluorine-18 incorporation yields.
- Maisonial-Besset, Aurélie,Serre, Audrey,Ouadi, Ali,Schmitt, Sébastien,Canitrot, Damien,Léal, Fernand,Miot-Noirault, Elisabeth,Brasse, David,Marchand, Patrice,Chezal, Jean-Michel
-
supporting information
p. 7058 - 7065
(2019/01/04)
-
- A self-assembled tetrapeptide that acts as a “turn-on” fluorescent sensor for Hg2+ ion
-
The tetrapeptide (Bz-ΔPhe(p-NPh2)-L-DOPA(protected)-L-Phe-L-Phe-OMe was designed to incorporate seven phenyl rings so that it's conformation, self-assembly and application in Hg2+ ions sensing could be studied. Peptide molecules adopted an overlapping β-turn of type III/III conformation in crystals. The peptide showed a highly selective turn-on response towards mercuric ion over other metal ions with a 10-fold enhancement in fluorescence intensity. This intensity change coupled with the selectivity of the peptide towards mercury allowed us to demonstrate simple colorimetric dip sensing of Hg2+ ions. The technique provides a highly selective and effective way to detect Hg2+ ions. The peptide also self-assembled into nanospheres with diameter ranges from 100 to 500 nm. Mercuric ion coordination enabled these peptide nanospheres to aggregate into well-defined nanoparticles. The enhanced fluorescence upon Hg2+ addition demonstrates that peptide scaffolds can be exploited in the development of different selective sensors.
- Tomar, Kalpana,Kaur, Gagandeep,Verma, Sandeep,Ramanathan, Gurunath
-
supporting information
p. 3653 - 3656
(2018/09/11)
-
- Synthesis and cytotoxicity of dinuclear platinum(II) complexes of (1S, 3S)-1,2,3,4-tetrahydroisoquinolines
-
A series of novel dinuclear platinum(II) complexes with (1S, 3S)-1,2,3,4-tetrahydroisoquinolines as the ligands were synthesized as potential anticancer agents in several steps starting from commercially available l-DOPA. The cytotoxicities of the series of dinuclear platinum(II) complexes of tetrahydroisoquinoline were tested against HCT-8, BEL-7402, A2780, MCF-7, Hela, A549 and BGC-823 cell lines by the MTT test. These complexes showed selective inhibition activity against cisplatin-insensitive cell line Skov3.
- Xu, Geng,Guo, Ju,Yan, Zheng,Wang, Nan,Liu, Zhan-Zhu
-
p. 186 - 188
(2013/06/26)
-
- Total synthesis of pyoverdin D
-
Pyoverdin D is an important siderophore that is used by the human pathogen Pseudomonas aeruginosa to import iron and gain a competitive advantage. This unique partially cyclic octapeptide bears four nonproteinogenic amino acids, including δN-formyl-δN-hydroxy-l-ornithine, and a catechol containing chiral chromophore. Here, we report the first total synthesis of pyoverdin D.
- Mashiach, Roi,Meijler, Michael M.
-
supporting information
p. 1702 - 1705
(2013/06/27)
-
- Synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via a Pictet-Spengler approach
-
A protocol for the diastereoselective synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via Pictet-Spengler condensation with L-DOPA or l-DOPA derivatives and 1H-indole-3-carbaldehydes is presented. The protocol is used for the successful synthesis of several tetrahydroisoquinolines as well as diketopiperazine fused analogues.
- Larsson, Rikard,Blanco, Narda,Johansson, Martin,Sterner, Olov
-
supporting information
p. 4966 - 4970
(2012/11/07)
-
- An Au(I)-catalysed allenamide cyclisation giving access to an α-vinyl-substituted tetrahydroisoquinoline building block
-
An Au(I)-catalysed intramolecular hydroarylation of an enantiopure allenamide has been achieved and has given access to a key α-vinyl- substititued tetrahydroisoquinoline. Additionally this has been accomplished in very high yield and high diastereoselectivity. Georg Thieme Verlag Stuttgart · New York.
- Singh, Sanjitpal,Elsegood, Mark R. J.,Kimber, Marc C.
-
scheme or table
p. 565 - 568
(2012/04/04)
-
- Method of synthesizing acetonide-protected catechol-containing compounds and intermediates produced therein
-
The inventors disclose here a novel, facile approach to the synthesis of acetonide-protected catechol-containing compounds having at least one amine group. In specific embodiments, the invention provides novel methods of synthesizing 3,4-dihydroxyphenylalanine (H-DOPA(acetonide)-OH (6)), Fmoc-protected H-DOPA(acetonide)-OH (Fmoc-DOPA(acetonide)-OH (7)), Fmoc-protected dopamine (Fmoc-dopamine(acetonide) (10)), TFA-protected dopamine (TFA-dopamine(acetonide) (13)) and acetonide-protected 4-(2-aminoethyl)benzene-1,2-diol (acetonide-protected dopamine (14)).
- -
-
Page/Page column 33-34
(2012/07/30)
-
- An organogel formed from a cyclic β-aminoalcohol
-
A new organogelator with unique structural feature of a cyclic β-aminoalcohol is presented as the first example of gelation by aminoalcohol through hydrogen-bonding between hydroxy and amine.
- Kang, Chuanqing,Bian, Zheng,He, Yabing,Han, Fushe,Qiu, Xuepeng,Gao, Lianxun
-
supporting information; scheme or table
p. 10746 - 10748
(2011/11/29)
-
- Synthesis and cytotoxicity of cis-dichloroplatinum (II) complexes of (1S,3S)-1,2,3,4-tetrahydroisoquinolines
-
A series of novel cisplatin-type platinum complexes with (1S,3S)-1,2,3,4-tetrahydroisoquinolines as the ligands were synthesized as potential anticancer agents in several steps starting from commercially available l-DOPA. The cytotoxicities of these compounds were tested against HCT-8, BEL-7402, A2780, MCF-7, Hela, A549 and BGC-823 cell lines by the MTT test. Some compounds exhibited better cytotoxic activity than cisplatin. The structure-activity relationship has been revealed.
- Xu, Geng,Yan, Zheng,Wang, Nan,Liu, Zhanzhu
-
scheme or table
p. 356 - 363
(2011/02/26)
-
- HIGH ADHESIVE ACRYLATE MONOMER AND METHOD FOR PREPARING THE SAME
-
A high adhesive acrylate monomer has a specific chemistry figure. This monomer may be easily prepared in a simplified way, and various linkers may be used between L-DOPA and an acrylate group attached to a tail of L-DOPA, so molecular weight and size of the entire material may be easily controlled. Also, various kinds of acrylate to be combined to a isocyanate compound used as a linker may be selected, so various molecules may be easily composed.
- -
-
Page/Page column 2; 3
(2010/11/03)
-
- A novel and efficient synthesis of DOPA and DOPA peptides by oxidation of tyrosine residues with IBX
-
An efficient route to 3,4-dihydroxylphenylalanine (DOPA) and DOPA peptides was described by oxidation of L-tyrosine and L-tyrosine derivatives with 2-iodoxybenzoic acid (IBX). DOPA was obtained after an situ reduction of the corresponding ortho-quinone with sodium dithionite. Oxidation reactions proceeded in good yields and high chemo- and regio-selectivity. The chirality of the DOPA residue was retained under the reaction conditions. The efficiency and the selectivity of the reaction were successfully tested using recyclable polymer-supported IBX.
- Bernini, Roberta,Barontini, Maurizio,Crisante, Fernanda,Ginnasi, Maria Cristina,Saladino, Raffaele
-
body text
p. 6519 - 6521
(2011/02/23)
-
- HIGH ADHESIVE ACRYLATE MONOMER AND METHOD FOR PREPARING THE SAME
-
A high adhesive acrylate monomer has a specific chemistry figure. This monomer may be easily prepared in a simplified way, and various linkers may be used between L-DOPA and an acrylate group attached to a tail of L-DOPA, so molecular weight and size of the entire material may be easily controlled. Also, various kinds of acrylate to be combined to a isocyanate compound used as a linker may be selected, so various molecules may be easily composed.
- -
-
Page/Page column 3-5
(2009/07/17)
-
- Efficient and practical protection of the catechol residue of 3,4-dihydroxy-phenylalanine (DOPA) derivative as acetonide
-
The acetonide formation of 3,4-dihydroxyphenylalanine (DOPA) derivative was realized under efficient and practical reaction conditions: the reaction of the methyl ester of DOPA in acetone-i-PrOH in the presence of 5 mol% of TsOH afforded the catechol side chain protected DOPA as an acetonide in quantitative yield; the workup procedure is a simple evaporation of the solvents. This methodology allows an access to the reaction in large scale. Georg Thieme Verlag Stuttgart.
- Soloshonok, Vadim A.,Ueki, Hisanori
-
p. 693 - 695
(2008/09/21)
-
- METHOD OF PREPARING DENDRITIC DRUGS
-
Synthetic design of drug-incorporated novel dendrimer structures for quantitatively controlled drug delivery. The dendritic drugs have better control and thus a quantitative drug release can be obtained. There are no prior art dendritic drugs that control release both sequentially and quantitatively like the dendritic drugs disclosed herein. The dendritic drugs are formed by incorporating multiple same type drug units or more than two different drug types into a dendritic cascade structure to form a dendrimer drug.
- -
-
Page/Page column 19-20; 28
(2010/11/28)
-
- Discovery of a novel nonphosphorylated pentapeptide motif displaying high affinity for Grb2-SH2 domain by the utilization of 3′-substituted tyrosine derivatives
-
The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. An impressive number of synthetic Grb2-SH2 domain inhibitors have been identified; however, clinical agents operating by this mechanism are lacking, due in part to the unique requirement of anionic phosphate-mimicking functionality for high SH2 domain-binding affinity or the extended peptide nature of most inhibitors. In the current study, a new binding motif was successfully developed by the incorporation of 3′-substituted tyrosine derivatives into a simplified nonphosphorylated cyclic pentapeptide scaffold (4), which resulted in high affinity Grb2-SH2 inhibitors without any phosphotyrosine or phosphotyrosine mimetics. The new L-amino acid analogues bearing an additional nitro, amino, hydroxy, methoxy or carboxy group at the 3′-position of the phenol ring of tyrosine were prepared in an orthogonally protected form suitable for solid-phase peptide synthesis using Fmoc protocols. The incorporation of these residues into cyclic peptides composed of a five-amino acid sequence motif, Xx′-Leu-(3′- substituted-Tyr)-Ac6c-Asn, provided a brand new class of nonphosphorylated Grb2 SH2 domain inhibitors with reduced size, charge and peptidic character. The highest binding affinity was exhibited by the 3′-aminotyrosine (3′-NH2-Tyr)-containing (R)-sulfoxide-cyclized pentapeptide (10b) with an IC50 = 58 nM, the first example with low-nanomolar affinity for a five-amino acid long sequence binding to Grb2-SH2 domain free of any phosphotyrosine or phosphotyrosine mimics. However, the incorporation of 3′-NO2-Tyr, 3′-OH-Tyr or 3′-OCH3-Tyr surrogates in the pentapeptide scaffold is detrimental to Grb2-SH2 binding. These observations were rationalized using molecular modeling. More significantly, the best Grb2-SH2 inhibitor 10b showed excellent activity in inhibiting the growth of erbB2-dependent MDA-MB-453 tumor cell lines with an IC50 value of 19 nM. This study is the first attempt to identify novel nonphosphorylated high affinity Grb2 SH2 inhibitors by the utilization of 3′-substituted tyrosine derivatives, providing a promising new strategy and template for the development of non-pTyr-containing Grb2-SH2 domain antagonists with potent cellular activity, which potentially may find value in chemical therapeutics for erbB2-related cancers.
- Song, Yan-Li,Peach, Megan L.,Roller, Peter P.,Qiu, Su,Wang, Shaomeng,Long, Ya-Qiu
-
p. 1585 - 1596
(2007/10/03)
-
- Synthesis and characterization of water-soluble and photostable L-DOPA dendrimers
-
A small drug molecule, L-DOPA, was converted into well-defined dendritic macromolecules. Their monodisperse nature was shown by NMR, MALDI-TOF-MS, and PAGE. A third-generation L-Dopa dendrimer contained 30 L-Dopa residues, which made up its core, branches, and periphery. Individual L-Dopa moieties in the dendrimer were connected to one another via hydrolyzable diester linkages. These Dopa dendrimers showed a 20-fold increase in aqueous solubility and enhanced photostability in solutions over L-Dopa under identical conditions.
- Tang, Shengzhuang,Martinez, Lynda J.,Sharma, Ajit,Chai, Minghui
-
p. 4421 - 4424
(2007/10/03)
-
- Synthesis and SAR of N-benzoyl-L-biphenylalanine derivatives: Discovery of TR-14035, a dual α4β7/α4β1 integrin antagonist
-
α4β1 and α4β7 integrins are key regulators of physiologic and pathologic responses in inflammation and autoimmune disease. The effectiveness of anti-integrin antibodies to attenuate a number of inflammatory/immune conditions provides a strong rationale to target integrins for drug development. Important advances have been made in identifying potent and selective candidates, peptides and peptidomimetics, for further development. Herein, we report the discovery of a series of novel N-benzoyl-L-biphenylalanine derivatives that are potent inhibitors of α4 integrins. The potency of the initial lead compound (1: IC50 α4β7/α4β1 =5/33 μM) was optimized via sequential manipulation of substituents to generate low nM, orally bioavailable dual α4β1/α4β7 antagonists. The SAR also led to the identification of several subnanomolar antagonists (134, 142, and 143). Compound 81 (TR-14035; IC50 α4β7/α4β1 =7/87 nM) has completed Phase I studies in Europe. The synthesis, SAR and biological evaluation of these compounds are described.
- Sircar, Ila,Gudmundsson, Kristjan S.,Martin, Richard,Liang, Jimmy,Nomura, Sumihiro,Jayakumar, Honnappa,Teegarden, Bradley R.,Nowlin, Dawn M.,Cardarelli, Pina M.,Mah, Jason R.,Connell, Samuel,Griffith, Ronald C.,Lazarides, Elias
-
p. 2051 - 2066
(2007/10/03)
-
- Design and synthesis of a novel L-Dopa - Entacapone codrug
-
A novel codrug, in which L-Dopa and entacapone are linked via a biodegradable carbamate spacer to form a single chemical entity, was synthesized and studied kinetically. This carbamate codrug provides adequate stability [t1/2 = 12.1 h (pH 1.2); 1.4 h (pH 5.0); 1.1 h (pH 7.4)] against chemical hydrolysis but rapidly hydrolyzes to L-Dopa and entacapone in liver homogenate (t1/2 = 7 min; pH 7.4) at 37°C. The therapeutical potential of this novel codrug is discussed.
- Lepp?nen, Jukka,Huuskonen, Juhani,Nevalainen, Tapio,Gynther, Jukka,Taipale, Hannu,J?rvinen, Tomi
-
p. 1379 - 1382
(2007/10/03)
-
- Chemo-enzymatic synthesis of optically active amino acids and peptides
-
The industrial alkaline protease, alcalase, is stable and active in a high concentration of organic solvents and useful as a biocatalyst for (i) diastereoselective hydrolysis of peptide esters and preparation of racemization-free peptides; (ii) selective incorporation of esters of D-amino acid into peptides in t-butanol via a selective hydrolysis of esters of D,L-amino acid, followed by using the unhydrolyzed D-esters as a nucleophile in a kinetically controlled peptide bond formation; (iii) resolution of esters of amino acid in 95% t-butanol/5% water, followed by saponification of the unreacted esters to offer both enantiomers with high yield and optical purity; (iv) completely resolve amino-acid esters with high yield and optical purity via in situ racemization of the unreacted antipode catalyzed by pyridoxal 5-phosphate; (v) cryobioorganic synthesis of peptides with increased yields 15%-40% of peptide bond formation by reaction at 5 °C instead of 25-30 °C of a kinetically controlled enzymatic reaction in alcohols.
- Chen, Shui-Tein,Wang, Kung-Tsung
-
p. 301 - 311
(2007/10/03)
-
- Synthesis of novel functionalised zinc phthalocyanines applicable in photodynamic therapy
-
The synthesis of several new phthalonitriles 3, 9, 14, 25, 33, and 36, functionalised with carboxyl groups, including two examples of amino acid derivatives is described. All new phthalonitriles were converted into their corresponding phthalocyaninatozinc compounds. The phthalocyanines, 2,3,9,10,16,17,23,24-octa(1-carboxyethyloxy)phthalocyaninatozinc (5), 2,9,16,23-tetra(2-amino-2-carboxyethyl)phthalocyaninatozinc (11), 2,9,16,23- tetra(1-carboxy-2-hydroxyethylaminocarbonyl)phthalocyaninatozinc (16), 1,8,15,22-tetra(carboxybutyl)phthalocyaninatozinc (27), 2,3,9,10,16,17,23,24- octa(carboxyalkyl)phthalocyaninatozinc (39), and the nonidentically substituted 9,10,16,17,23,24-hexa(carboxyalkyl)-2-[4-(N- succinimidyloxycarbonyl)butyl]phthaloyaninatozinc (41) are all sufficiently soluble in water. The nonidentically-substituted compounds are important due to their selective binding to tumor-selective antibodies. UV/Vis-spectroscopy was used to investigate the effect of more or less sterically-demanding substituents in the periphery of the phthalocyanines towards aggregation. The phototoxicity towards cancer cells of some of the new compounds was investigated in several in-vitro experiments.
- Drechsler, Ulf,Pfaff, Mirjam,Hanack, Michael
-
p. 3441 - 3453
(2007/10/03)
-
- Photochemical Oxygenation of Phenols by Pyrimidopteridine N-Oxide. Comparative Studies with Pyridazine and Isoalloxazine N-Oxides
-
1,3,7,9-Tetrabutylpyrimidopteridine-2,4,6,8(1H,3H,7H,9H)-tetraone 5-oxide 1 transfers its N-oxide oxygen to phenols, i.e., phenol 5, p-cresol 6, L-tyrosine methyl ester 7, and p-hydroxyacetanilide (acetaminophen) 8, under photochemical conditions to give the corresponding dihydric phenols as major products without any accompanying photochemical intramolecular rearrangements of the N-oxide group taking place.This oxygenation is reasonably explained in terms of a photo-induced single electron transfer (SET) followed by oxygen-atom transfer (the SET mechanism) which occurs via the initial formation of a charge-transfer complex between compound 1 and the phenols employed.Comparative experiments with 3,10-dibutylisoalloxazine 5-oxide 3 and 3-methylpyridazine 2-oxide 4 well demonstrate the simplicity and the mechanistic characteristics of the photochemistry of compound 1.
- Sako, Magoichi,Ohara, Seiji,Hirota, Kosaku,Maki, Yoshifumi
-
p. 3339 - 3344
(2007/10/02)
-
- Novel, transient pro-drug forms of L-DOPA
-
There is provided, novel, transient pro-drug forms of L-DOPA (3,4-dihydroxy-L-phenylalanine), having the formula: STR1 wherein n represents an integer of from 2 to 50 with respect to formula (V-A), and wherein n represents an integer of from 1 to 50 with respect to formula (V-B); R represents a hydrogen atom, an acyl group, STR2 --CO-pyridyl, or --CO--R3, wherein R3 is the residue of any N,N-C1 -C2 dialkylamino acid or a C4 -C6 cycloalkylamino acid; R1 represents --OH, --O-lower alkyl, --O-benzyl, or a naturally occurring protein amino acid; and R2 represents STR3 --CO-pyridyl, a naturally occurring protein amino acid, 3',4'-L-diacyloxy phenylalanine, or --CO-R3. These compounds are all useful in the treatment of Parkinson's Disease.
- -
-
-