- BORON CLUSTER-COUPLED COMPOUND
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To provide a novel boron-containing compound which increases intratumorous accumulation and tumor retention, and is efficiently taken into a tumor cell.SOLUTION: The present invention relates to a compound represented by formula (I) in the figure or a salt thereof. [In the formula, X represents a divalent to pentavalent organic group; Y represents a linker structure; R represents a monovalent group comprising boron clusters; and n represents 2, 3, 4 or 5.SELECTED DRAWING: None
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Paragraph 0271; 0273-0275
(2021/03/05)
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- LIQUID COMPOSITIONS COMPRISING A LEVODOPA AMINO ACID CONJUGATE AND USES THEREOF
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Disclosed herein are liquid pharmaceutical formulations comprising levodopa amino acid conjugates that may further comprise a decarboxylase inhibitor, such as carbidopa, an antioxidant, a solvent, or any other pharmaceutically acceptable excipient. Further disclosed are methods of treating generative conditions and/or conditions characterized by reduced levels of dopamine in the brain, such as Parkinson's disease, comprising administering the disclosed liquid pharmaceutical formulations. Disclosed also are LDAA conjugate compounds.
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Page/Page column 80
(2021/03/13)
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- PROTAC targeting the degradation of tyrosinase and its applications
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The present invention relates to PROTAC targeting tyrosinase and its applications, belonging to the technical field of new raw materials for skin whitening cosmetics and skin disease treatment drugs. The technical problem solved by the present invention is to provide a compound using PROTAC targeting the degradation of tyrosinase and its salts, prodrugs, hydrates or solvates. The PROTAC molecule, whose structural formula is shown in formula I. The present invention by different types, different chain lengths of the linker will be tyrosinase ligand and E3 ligase ligand coupling, successfully prepared a series of targeted tyrosinase PROTAC molecules, can effectively target the target protein, and reduce the content of tyrosinase in the cell, while having a good in vitro reducing melanin effect, low toxicity to normal cells, in line with the characteristics of high efficiency and low toxicity.
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Paragraph 0040; 0060-0065
(2021/12/07)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF PAIN AND DEPENDANCE DISORDERS
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Provided herein are (e.g., controlled release) compositions for the treatment of acute or chronic diseases or disorders. Described herein are processable opioid conjugates. Also described herein are compositions and methods for the treatment of central nervous system (CNS) diseases or disorders including chronic pain (e.g., cancer pain), acute pain, opioid addiction, alcohol addiction, alcohol dependence, opioid-induced constipation, and narcotic depression. Said compositions and methods comprise opioid agonists and/or opioid antagonists, which demonstrate CNS activity and/or other desirable activities. Injection of said compositions subcutaneously or intraspinally provides therapeutic benefit to individuals suffering from CNS diseases or disorders
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Paragraph 00279
(2021/02/12)
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- Delivery of a system xc?inhibitor by a redox-responsive levodopa prodrug nanoassembly for combination ferrotherapy
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A comprehensive understanding of ferroptosis signaling pathways significantly contributes to the advances in cancer ferrotherapy. Herein, we constructed a self-assembled prodrug nanosystem targeting system xc?, a key regulator for ferroptosis, to amplify the therapeutic efficacy of cancer ferrotherapy. The prodrug nanosystem is assembled between sulfasalazine (SSZ, a ferroptosis resistance inhibitor) and disulfide-bridged levodopa (DSSD) that can chelate Fe2+ions to form SSZ-Fe2+@DSSD, and the resulting nanoassembly can not only inhibit ferroptosis resistance, but also generate ROS in the tumor microenvironment. Whereas the prodrug nanosystem is stable in the physiological environment, it becomes unstable in the tumoral and intracellular reductive microenvironment, where the disulfide linkers are disrupted by high levels of glutathione (GSH), triggering the release of active Fe2+and SSZ. Under the Fenton reaction, the released Fe2+thus can induce ferroptosis, which is amplified by SSZ-mediated inhibition of ferroptosis resistance to synergistically improve the therapeutic efficacy of ferroptosis. Our study thus provides an innovative prodrug strategy to advance anticancer ferroptosis.
- Chen, Yuan,Huang, Yong,Li, Bowen,Ping, Yuan,Tang, Honglin,Xia, Hongguang,Xin, Huhu,Zhang, Fu
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supporting information
p. 7172 - 7181
(2021/09/22)
-
- An alternative approach to the synthesis of the three fragments of anachelin H
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The synthesis of the fully protected peptide, polyketide and alkaloid fragments of anachelin H is presented. The peptide fragment was prepared using a liquid phase peptide synthesis; the polyketide fragment was synthetized using a cross metathesis and an intramolecular oxa-Michael reaction as the key steps to introduce the desired stereochemistry; finally, the alkaloid fragment was obtained by an oxidative cyclization of a catechol derivative using potassium ferricyanide. The synthesis of all fragments was based on the use of natural amino acids as sources of asymmetry. The independent synthesis of the three fragments should allow more efficient biological studies on the fragments instead of the whole natural product. Experiments to illustrate the coupling of fragments and the effectiveness of the convergent strategy are also described.
- Gamba-Sánchez, Diego,Garzón-Posse, Fabián,Prunet, Jo?lle
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p. 2702 - 2715
(2020/04/17)
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- PANTETHEINE DERIVATIVES AND USES THEREOF
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The present disclosure relates to compounds of Formula (I), (II), or (II'): (I), (II), (II'), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.
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Paragraph 2121
(2020/06/19)
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- Water-soluble L-DOPA esters
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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.
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Paragraph 0103
(2018/05/24)
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- Nitrogen (oxygen) heterocyclic pentane - 2 - one (thione) compound, pharmaceutical composition, preparation method and use thereof
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The invention belongs to the field of pharmacology, and relates to aza (oxa)-cyclopentane-2- ketone (thione) compounds shown in the formula I, medicine compositions thereof, a preparation method, applications in preparation of medicines treating diabetes and glucolipid metabolism, and especially applications in preparation of medicines treating II-type diabetes.
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Paragraph 0091; 0092
(2017/08/25)
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- MULTIMODAL CONTRAST AND RADIOPHARMACEUTICAL AGENT FOR AN IMAGING AND A TARGETED THERAPY GUIDED BY IMAGING
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The present invention relates to a multimodal contrast and radiopharmaceutical agent for an imaging and a targeted therapy guided by imaging.
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Page/Page column 36
(2013/06/05)
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- NOVEL COMPOUND AND MEDICAL USE THEREOF
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Provided is a levodopa prodrug that overcomes the problems attributed to the blood kinetics of levodopa such as large number of doses and the incidence of side effects due to frequent dosing. (2S)-2-Amino-3-(3,4-bis((2-(benzoyloxy)-2-methylpropanoyl)oxy)p
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Paragraph 0353-0354
(2013/09/26)
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- Indolyl-Substituted Pyrazino-Quinolines and Their Use for the Treatment of Cancer
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There is provided compounds of formula I, wherein the wedged bonds, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, Rsu
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Page/Page column 12-14
(2012/06/30)
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- Synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via a Pictet-Spengler approach
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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
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supporting information
p. 4966 - 4970
(2012/11/07)
-
- NEW COMPOUNDS AND MEDICAL USE
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There is provided compounds of formula (I), wherein the wedged bonds, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R
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Page/Page column 31
(2011/01/12)
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- INDOLYL-SUBSTITUTED PYRAZINO-QUINOLINES AND THEIR USE FOR THE TREATMENT OF CANCER
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There is provided compounds of formula I, wherein the wedged bonds, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, Rsu
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Page/Page column 38
(2011/01/12)
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- Design, synthesis, and preliminary pharmacological evaluation of new imidazolinones as l-DOPA prodrugs
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l-DOPA, the immediate biological precursor of dopamine, is still considered the drug of choice in the treatment of Parkinson's disease. However, therapy with l-DOPA is associated with a number of acute problems. With the aim to increase the bioavailability after oral administration, we designed a multi-protected l-DOPA prodrugs able to release the drug by both spontaneous chemical or enzyme catalyzed hydrolysis. The new compounds have been synthesized and preliminarily evaluated for their water solubility, log P, chemical stability, and enzymatic stability. The results indicate that the incorporation of the amino acidic moiety of l-DOPA into an imidazoline-4-one ring provides prodrugs sufficiently stable to potentially cross unchanged the acidic environment of the stomach, and to be absorbed from the intestine. They also might be able to release l-DOPA in human plasma after enzymatic hydrolysis. The ability of prodrugs 6a-b to increase basal levels of striatal DA, and influence brain neurochemistry associated with dopaminergic activity following oral administration, as well as the radical-scavenging activity against DPPH for compounds 6a-b and 15a are also reported.
- Giorgioni, Gianfabio,Claudi, Francesco,Ruggieri, Sabrina,Ricciutelli, Massimo,Palmieri, Giovanni F.,Stefano, Antonio Di,Sozio, Piera,Cerasa, Laura S.,Chiavaroli, Annalisa,Ferrante, Claudio,Orlando, Giustino,Glennon, Richard A.
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experimental part
p. 1834 - 1843
(2010/05/02)
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- ESSENTIAL FATTY ACID COMPOUNDS
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The invention provides compounds which include L-DOPA or dopamine linked to an essential fatty acids. The general formula is set out below: R1-Z-O-(CH2)n-CH(R3)-(CH2)mO-Y-R2. Rs
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Page/Page column 12-13
(2010/10/03)
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- Protein-resistant surfaces through mild dopamine surface functionalization
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The synthesis and evaluation of new dopamine-based catechol anchors coupled to poly(ethylene glycol) (PEG) for surface modification of TiO2 are reported. Dopamine is modified by dimethylamine-methylene (7) or trimethylammonium-methylene (8) groups, and the preparation of mPEG-Glu di-dopamine polymer 11 is presented. All these PEG polymers allow stable adlayers on TiO2 to be generated through mild dip-and-rinse procedures, as evaluated both by variable angle spectroscopic ellipsometry and X-ray photoelectron spectroscopy. The resulting surfaces substantially reduced protein adsorption upon exposure to full human serum.
- Wach, Jean-Yves,Malisova, Barbora,Bonazzi, Simone,Tosatti, Samuele,Textor, Marcus,Zuercher, Stefan,Gademann, Karl
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supporting information; experimental part
p. 10579 - 10584
(2009/12/04)
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- Diastereoselective intramolecular α-amidoalkylation reactions of L-DOPA derivatives. Asymmetric synthesis of pyrrolo[2,1-a]isoquinolines
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Stereocontrolled intramolecular α-amidoalkylation reactions of L-DOPA-derived succinimides have been studied. Addition of MeLi to nonracemic succinimides 9a-d yields oxoamides, which are cyclized upon treatment with Lewis or protic acids to afford (5S,10b
- Garcia, Eva,Arrasate, Sonia,Lete, Esther,Sotomayor, Nuria
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p. 10368 - 10374
(2007/10/03)
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- A biomimetic route to the peptide alkaloid anachelin
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A postulated biogenesis forms the basis for a synthetic route to the natural product anachelin H (1). Key steps include a tellurium-mediated, oxidative aza annulation and a Claisen condensation under mild conditions. Experiments with a model substrate ind
- Gademann, Karl,Bethuel, Yann
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p. 3327 - 3329
(2007/10/03)
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- Aromatic derivatives with HIV integrase inhibitory properties
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A compound of formula I′ and pharmaceutically acceptable derivatives thereof including, for example, where applicable or appropriate pharmaceutically acceptable salts thereof. Ar and Ar′ are aromatic or aryl type groups. The compounds have HIV integrase inhibitory properties. Ar, Ar′ and W may be as defined in the specification.
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- A new efficient synthetic process for the construction of the pentacyclic core of marine alkaloid ecteinascidins
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The pentacyclic core of ecteinascidins was constructed from two fundamental building blocks, the 1,2,3,4-tetrahydroisoquinoline derivative and the substituted phenylalanine derivative, via 8 steps using readily available L-Dopa as starting material. The k
- Tang, Ye-Feng,Liu, Zhan-Zhu,Chen, Shi-Zhi
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p. 7091 - 7094
(2007/10/03)
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- Synthesis of peptides containing DOPA (3,4-dihydroxyphenylalanine)
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Proteins from coral reefs structures, eggshells, and marine mollusk adhesives all contain the amino acid 3,4-dihydroxyphenylalanine (DOPA). The insoluble nature of these materials has hampered characterization and turned our efforts toward work with small peptide mimics. In this paper, we present the syntheses of various DOPA derivatives: Boc-DOPA, Fmoc-DOPA, DOPA(TBDMS)2, DOPA(TBDPS)2, Boc-DOPA(TBDPS)2, Fmoc-DOPA(TBDMS)2, and Fmoc-DOPA(TBDPS)2 (where Boc=tert-butyloxycarbonyl, Fmoc=9-fluorenylmethyloxycarbonyl, TBDMS=tert-butyldimethylsilyl, and TBDPS=tert-butyldiphenylsilyl). These DOPA compounds were used to prepare peptides of various sequences. The synthetic procedure described provides an efficient route to DOPA-containing peptides in which sidechain deprotection and cleavage from resin can be accomplished in one step.
- Sever, Mary J,Wilker, Jonathan J
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p. 6139 - 6146
(2007/10/03)
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- Synthesis of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine as potential prodrug of L-dopa
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The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described. Prodrug 9 possesses a good lipophilicity (log P=2.153 ± 0.017), is stable in aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it is turned into L-Dopa. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Cingolani, Gian Mario,Di Stefano, Antonio,Mosciatti, Barbara,Napolitani, Fabrizio,Giorgioni, Gianfabio,Ricciutelli, Massimo,Claudi, Francesco
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p. 1385 - 1388
(2007/10/03)
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- PEPTIDE DERIVATIVES AND ANGIOTENSIN IV RECEPTOR AGONIST
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Short-chain peptide derivatives acting on angiotensin IV receptor at low concentrations. Because of agonistically acting on angiotensin IV receptor, the novel peptide derivatives of the present invention represented by the following formula (1) are useful as remedies for various diseases in which angiotensin IV participates:
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- EPOXYSUCCINIC ACID DERIVATIVES
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A compound of the general formula: STR1 wherein R 1 represents a carboxyl group which may optionally be esterified or amidated; R 2 represents a cyclic group which may optionally be substituted or a polar group; n is an integer of 0 to 6; R 3 represents hydrogen or a hydrocarbon residue which may optionally be substituted; R 4 represents (1) a hydrocarbon residue which is substituted by an optionally protected amino group or (2) an alkenyl group; or R 3 and R 4 may be combined with the adjacent nitrogen atom to form a heterocyclic group containing at least two hetero atoms, or a salt thereof.The compound or a salt thereof of the present invention inhibits thiol proteases such as cathepsin L and B and serves well as a prophylactic/therapeutic agent for bone diseases such as osteoporosis.
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- pGlu-L-Dopa-Pro: A tripeptide prodrug targeting the intestinal peptide transporter for absorption and tissue enzymes for conversion
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Purpose. The purpose of this study is to investigate the characteristics of pGlu-L-Dopa-Pro as a prodrug of L-Dopa. Methods. pGlu-L-Dopa-Pro and L-Dopa-Pro were synthesized using the standard procedures of peptide synthesis. The conversion of pGlu-L-Dopa-Pro to L-Dopa was studied using pyroglutamyl aminopeptidase I and prolidase. With rats as the animal model, the stability of pGlu-L-Dopa-Pro in intestinal homogenates was determined, then the transport characteristics of pGlu-L-Dopa-Pro were studied using in-situ perfusion and Ussing chambers. Results. pGlu-L-Dopa-Pro, relatively stable in intestinal homogenates and intestinal fluid, had a dimensionless permeability of 1.8 at 0.04 mM. Its intestinal permeability was significantly inhibited by 20 mM captopril, by a mixture of dipeptides, 80 mM Gly-Gly and 5 mM Gly-Pro, and by 2 mM cephradine. Further, in Ussing chambers, its mucosal to serosal permeability decreased dramatically with concentration. Conversion studies showed that pGlu-L-Dopa-Pro was degraded by pyroglutamyl aminopeptidase I, an enzyme releasing the N-terminal pyroglutamic acid, with Vmax and Km of 0.6 μmole/min/g protein and 21 mM, respectively, and that L-Dopa-Pro was degraded by prolidase with Vmax and Km of 44 μmole/min/g protein and 0.48 mM, respectively. Conclusions. This tripeptide, a potential prodrug of L-Dopa, is absorbed by the intestinal peptide transporter, is relatively stable in the gut wall, and is converted to L-Dopa by peptidases with the cleavage by pyroglutamyl aminopeptidase I to L-Dopa-Pro as the rate limiting step.
- Bai
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p. 1101 - 1104
(2007/10/03)
-
- Method of increasing lean meat in edible animals
-
The present invention discloses substituted 1,3-benzodioxoles which possess anti-diabetic and/or anti-hyperglycemic and/or anti-obesity properties in humans and other animals.
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-
- Substituted 5-(2-((2-aryl-2-hydroxyethyl)amino)propyl)-1,3-benzodioxoles
-
The present invention discloses substituted 1,3-benzodioxoles which possess anti-diabetic and/or anti-hyperglycemic and/or anti-obesity properties in humans and other animals.
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-
- Dihydrocoumarin derivatives
-
Process for obtaining 5,6 or 6,7 or 7,8 dihydroxy coumarin or derivatives thereof, which are useful for lower blood pressure and for chemical sympathectomy by oxidizing 2,3 or 3,4 or 4,5 dihydroxyphenyl-propionic acid or derivatives thereof, and novel coumarin derivatives of the process.
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