- Synthesis and characterization of novel chitosan-dopamine or chitosan-tyrosine conjugates for potential nose-to-brain delivery
-
This work aims to the synthesis of novel carboxylated chitosan-dopamine (DA) and -tyrosine (Tyr) conjugates as systems for improving the brain delivery of the neurotransmitter DA following nasal administration. For this purpose, ester or amide conjugates were synthesized by N,N-dicyclohexylcarbodiimide (DCC) mediated coupling reactions between the appropriate N-tert-butyloxycarbonyl (Boc) protected starting polymers N,O-carboxymethyl chitosan and 6-carboxy chitosan and DA or O-tert-Butyl-L-tyrosine-tert-butyl ester hydrochloride. The resulting conjugates were characterized by FT-IR and 1H- and 13C NMR spectroscopies and their in vitro mucoadhesive properties in simulated nasal fluid (SNF), toxicity and uptake from Olfactory Ensheathing Cells (OECs) were assessed. Results demonstrated that N,O-carboxymethyl chitosan-DA conjugate was the most mucoadhesive polymer in the series examined and, together with the 6-carboxy chitosan-DA-conjugate were able to release the neurotransmitter in SNF. The MTT assay showed that the starting polymers as well as all the prepared conjugates in OECs resulted not toxic at any concentration tested. Likewise, the three synthesized conjugates were not cytotoxic as well. Cytofluorimetric analysis revealed that the N,O-carboxymethyl chitosan DA conjugate was internalized by OECs in a superior manner at 24 h as compared with the starting polymer. Overall, the N,O-CMCS-DA conjugate seems promising for improving the delivery of DA by nose-to-brain administration.
- Cassano, Roberta,Conese, Massimo,Di Gioia, Maria Luisa,Di Gioia, Sante,Mandracchia, Delia,Pellitteri, Rosalia,Trapani, Adriana,Tripodo, Giuseppe,Trombino, Sonia
-
-
Read Online
- Lithium Ion Recognition with Nanofluidic Diodes through Host-Guest Complexation in Confined Geometries
-
The lithium ion recognition is receiving significant attention because of its application in pharmaceuticals, lubricants and, especially, in energy technology. We present a nanofluidic device for specific lithium ion recognition via host-guest complexatio
- Ali, Mubarak,Ahmed, Ishtiaq,Ramirez, Patricio,Nasir, Saima,Mafe, Salvador,Niemeyer, Christof M.,Ensinger, Wolfgang
-
-
Read Online
- 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)
-
- Fluorodesulfurization of Thionobenzodioxoles with Silver(I) Fluoride
-
Difluorobenzodioxole is an important functional group found in both pharmaceuticals and agrochemicals. The late-stage introduction of this functional group is challenged by typical fluorination conditions of HF and strong oxidants. Here, we demonstrate that a range of difluorobenzodioxoles can be prepared from catechols in two steps through conversion into thionobenzodioxoles, followed by desulfurative fluorination with silver(I) fluoride. These mild reaction conditions are compatible with a variety of functional groups and enable access to a range of functionalized difluorobenzodioxoles.
- Newton, Josiah J.,Brooke, Alan J.,Duhamel, Bastian,Pulfer, Jason M.,Britton, Robert,Friesen, Chadron M.
-
p. 13298 - 13305
(2020/11/26)
-
- METHODS AND INTERMEDIATES FOR PREPARING DEUTETRABENAZINE
-
Disclosed is a process for the preparation of deutetrabenazine and intermediates useful in the preparation thereof. Disclosed are also process for making amorphous deutetrabenazine.
- -
-
Page/Page column 40
(2019/07/17)
-
- BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2
-
The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Paragraph 0216; 0217
(2018/07/05)
-
- Bioinspired Syntheses of the Pyridoacridine Marine Alkaloids Demethyldeoxyamphimedine, Deoxyamphimedine, and Amphimedine
-
Efficient bioinspired syntheses of the biologically active pyridoacridine marine alkaloids demethyldeoxyamphimedine, deoxyamphimedine, and amphimedine are reported. Reaction of styelsamine D, prepared via an optimized route starting from Boc-dopamine, wit
- Khalil, Iman M.,Barker, David,Copp, Brent R.
-
p. 282 - 289
(2016/01/15)
-
- DIMETHOXYPHENYL INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2
-
Described are dimethoxyphenyl inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Paragraph 00175
(2016/09/15)
-
- Hexagonal magnetite nanoprisms: Preparation, characterization and cellular uptake
-
The capacity of iron oxide nanocrystals to heat tissue when subjected to an alternating magnetic field (AMF hyperthermia) is shape-selective. Although iron oxide nanostructures with numerous shapes have been synthesized to date, hexagonal Fe3O
- Wang,Shrestha,Basel,Pyle,Toledo,Konecny,Thapa,Ikenberry,Hohn,Chikan,Troyer,Bossmann
-
supporting information
p. 4647 - 4653
(2015/06/16)
-
- BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2
-
The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. (I)
- -
-
Paragraph 00161
(2015/06/08)
-
- METHODS OF TREATING ABNORMAL MUSCULAR ACTIVITY
-
Methods for treating abnormal muscular activity are disclosed. The methods may be performed remotely and permit monitoring of a subject outside a healthcare provider's office.
- -
-
Paragraph 0193
(2015/06/08)
-
- BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2
-
The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. (Formula (I))
- -
-
Paragraph 00187
(2015/08/06)
-
- Brain-specific delivery of dopamine mediated by N, N-dimethyl amino group for the treatment of Parkinson's disease
-
Parkinson's disease (PD) has become one of the most deadly diseases due to a lack of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3- (dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was investigated both in vitro and in vivo by comparing with L-DOPA and another derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via an active transport process. The increased cellular uptake of PDDP was proven to be mediated by putative pyrilamine cationic transporters. Following intravenous administration, the concentration of PDDP in the brain was 269.28-fold and 6.41-fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally, PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6-OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus, N,N-dimethyl amino group-based PDDP represents an effective and safe treatment for PD.
- Li, Yanping,Zhou, Yangyang,Qi, Bowen,Gong, Tao,Sun, Xun,Fu, Yao,Zhang, Zhirong
-
p. 3174 - 3185
(2014/11/07)
-
- NOVEL HIGH PENETRATION DRUGS AND THEIR COMPOSITIONS THEREOF FOR TREATMENT OF PARKINSON DISEASES
-
One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolit
- -
-
Paragraph 00119; 00120
(2014/09/29)
-
- Bifunctional catechol based linkers for modification of TiO2 surfaces
-
Bifunctional linkers for modification of TiO2 nanoparticles were prepared containing a catechol group for TiO2 surface attachment and a maleimide and alkyne group for Michael addition and Cu catalysed Huisgen cycloaddition respectively. Peptide and fluorophore functionalised TiO 2 NPs were prepared, different purification methodologies were explored and conjugates were characterized using a range of methods.
- Geiseler, Bianca,Fruk, Ljiljana
-
scheme or table
p. 735 - 741
(2012/04/04)
-
- 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)
-
- Nucleophilic deoxyfluorination of catechols
-
Nucleophilic deoxyfluorinaiton of one of the two hydroxyl groups of catechols has been developed via the Umpolung concept. This method was successively applied to naturally occurring catechols, such as catechins and dopamine, to produce novel fluorinated
- Nemoto, Hiroyuki,Nishiyama, Tsuyoshi,Akai, Shuji
-
supporting information; experimental part
p. 2714 - 2717
(2011/06/28)
-
- BENZOQUINOLONE INHIBITORS OF VMAT2
-
The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof. Formula (I)
- -
-
Page/Page column 41
(2011/12/14)
-
- A new and efficient route for the synthesis of naturally occurring catecholamines
-
Catecholamines, sympathomimetic drugs and adrenergic receptor antagonists, have been prepared by a regioselective oxidation of the corresponding 4-hydroxyphenethylamine derivatives by 2-iodoxybenzoic acid (IBX) in homogeneous as well as in heterogeneous conditions and followed by cleavage of the amino protective group. By using polymer-supported IBX, after the first oxidation, the oxidant can be recovered, regenerated, and efficiently reused for several additional times. An efficient, easy and green procedure for the synthesis of N-(methoxycarbonyl)dopamine, key component of many pharmaceuticals, has also been reported. Georg Thieme Verlag Stuttgart.
- Bernini, Roberta,Crisante, Fernanda,Barontini, Maurizio,Fabrizi, Giancarlo
-
experimental part
p. 3838 - 3842
(2010/03/30)
-
- Synthesis and pharmacological testing of polyaminoquinolines as blockers of the apamin-sensitive Ca2+-activated K+ channel (SKCa)
-
The synthesis and pharmacological testing of a series of non-peptidic blockers of the SKCa (SK-3) channel is described. Target compounds were designed to mimic the spatial relationships of selected key residues in the energy-minimised structure of the octadecapeptide apamin, which are a highly potent blocker of this channel. Structures consist of a central unit, either a fumaric acid or an aromatic ring, to which are attached two alkylguanidine or two to four alkylaminoquinoline substituents. Potency was tested by the ability to inhibit the SKCa channel-mediated after-hyperpolarization (AHP) in cultured rat sympathetic neurones. It was found that bis-aminoquinoline derivatives are significantly more potent as channel blockers than are the corresponding guanidines. This adds to the earlier evidence that delocalisation of positive charge through the more extensive aminoquinolinium ring system is important for effective channel binding. It was also found that an increase in activity can be gained by the addition of a third aminoquinoline residue to give non-quaternized amines which have submicromolar potencies (IC50 = 0.13-0.36 μM). Extension to four aminoquinoline residues increased the potency to IC50 = 93 nM.
- Fletcher, David I.,Ganellin, C. Robin,Piergentili, Alessandro,Dunn, Philip M.,Jenkinson, Donald H.
-
p. 5457 - 5479
(2008/09/18)
-
- Dopamine as a robust anchor to immobilize functional molecules on the iron oxide shell of magnetic nanoparticles
-
We report on the use of dopamine (DA) as a robust molecular anchor to link functional molecules to the iron oxide shell of magnetic nanoparticles. Using nitrilotriacetic acid (NTA) as the functional molecule, we created a system with an M/Fe2O
- Xu, Chenjie,Xu, Keming,Gu, Hongwei,Zheng, Rongkun,Liu, Hui,Zhang, Xixiang,Guo, Zhihong,Xu, Bing
-
p. 9938 - 9939
(2007/10/03)
-
- Metal-assisted assembly and stabilization of collagen-like triple helices
-
Single-chain and TRIS-assembled collagen mimetic peptide structures incorporating catechol groups were synthesized. When 1/3 equiv of Fe3+ was added to the single-chain compound in 50 mM CAPS buffer (pH 10), the 1:3 Fe3+-catechol complex that formed acted as an N-terminal scaffold to assemble the triple helix. When 1 equiv of Fe3+ was added to the TRIS-assembled compound in the buffer solution, the Fe3+-catechol complex acted as an extra C-terminal scaffold, which lead to a triple helix with both termini tethered. The formation of this C-terminal complex increased the Tm by a remarkable 22 °C! Copyright
- Cai, Weibo,Kwok, Sen Wai,Taulane, Joseph P.,Goodman, Murray
-
p. 15030 - 15031
(2007/10/03)
-
- Novel pyrazolo- and pyrrolo-pyrimidines and uses thereof
-
The invention relates to compounds of the general formula: in which RA-RC and W are as defined herein, and to their preparation and use.
- -
-
-
- Purine derivatives
-
This invention relates to compounds of the general formula: in which RA, RB, RC and RD are as defined herein, and to their preparation and use.
- -
-
-
- Quinoline-(C=O)-(multiple amino acids)-leaving group compounds for pharmaceutical compositions and reagents
-
This invention concerns compounds and a pharmaceutical composition of the structure: wherein: R1 is selected from the group consisting of alkyl, substituted alkyl, aryl, and substituted aryl which group will produce a natural amino acid structure or an unnatural amino acid structure, and the carbon adjacent to R1 is in the D or L configuration; R2 is selected from the group consisting of —F ?and wherein R3 and R4 are each selected from the group consisting of hydrogen, alkyl, fluoro, chloro, carboxyl, alkoxy, alkyl carbonyl, aryl carbonyl, and amino; R5 and R5′ are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, fluoro, chloro, carboxy, alkoxy, alkyl carbonyl, aryl carbonyl, and amino, R6 is selected from the group consisting of alkyl having 1 to 10 carbon atoms, aryl or substituted aryl, and m is 1, 2 or 3. These compounds are reagents and pharmaceutical compositions have pro-drug and apoptosis properties and are useful in a variety of therapies, for diseases such as arthritis, ALS, MS, and the like.
- -
-
-
- Synthesis and biological studies of glycosyl dopamine derivatives as potential antiparkinsonian agents
-
A new approach to deliver dopamine into the central nervous system, based on the use of D-glucose as transportable agent, has been studied. Glycosyl dopamine derivatives bearing the sugar moiety linked to either the amino group or the catechol ring of dopamine through amide, ester or glycosidic bonds were synthesised as potential antiparkinsonian agents. Studies on the binding to dopamine D2 receptor, in vitro stability, and locomotive effect in mice of the synthetic glycoconjugates are reported. Copyright (C) 2000 Elsevier Science Ltd.
- Fernandez, Caridad,Nieto, Ofelia,Rivas, Emilia,Montenegro, Gisela,Fontenla, Jose A.,Fernandez-Mayoralas, Alfonso
-
p. 353 - 365
(2007/10/03)
-
- Increasing 5-lipoxygenase inhibitory activities by oxidative conversion of o-methoxyphenols to catechols using a Cu2+ - ascorbic acid - O2 system
-
Several complicated o-methoxyphenols were oxidized with high selectivity to catechols by a Cu2+ - ascorbic acid - O2 system. In this way, the RBL-1 5-lipoxygenase inhibitory activities of o-methoxyphenols were greatly increased. [6]-Norgingerol (4), a novel compound derived from [6]-gingerol (3), shows promise as a lead compound for new drugs because of its high inhibitory potency (IC50 = 5.0 x 10-8 M).
- Aihara,Higuchi,Hirobe
-
p. 842 - 844
(2007/10/02)
-
- O2-Cu2+-ASCORBIC ACID: A NOVEL OXIDATION SYSTEM FOR THE HIGHLY SELECTIVE O-DEALKYLATION OF 2-ALKOXYPHENOLS
-
The novel oxidation system "O2-Cu2+-ascorbic acid" is a selective reagent for the oxidative O-dealkylation of 2-alkoxyphenols and affords catechols in good yield.KEYWORDS - O-dealkylation; ascorbic acid; copper ion; oxidation; 2-alkoxyphenol; vanillin; dopamine; guaiacol; catechol
- Aihara, Kazuhiro,Higuchi, Tsunehiko,Hirobe, Masaaki
-
p. 837 - 840
(2007/10/02)
-
- A Convenient Synthesis of (Acyloxy)alkyl α-Ethers of Phenols
-
(Acyloxy)alkyl α-ethers (1) of phenols, thiophenol, and catechols have been prepared in good yield by their alkylation with (acyloxy)alkyl α-chlorides or iodides in acetone in the presence of K2CO3.In addition, one example of an (acylthio)alkyl α-ether was prepared.Either partial or complete acylation rather than alkylation on oxygen took place if the α-iodide was not used except for reactions of 3-chloro-1(3H)-isobenzofuranone with phenol or catechol or the reaction of (benzoylthio)methyl chloride with β-estradiol.It is suggested that more alkylation takes place with iodide as a leaving group because of the tighter transition state that develops with the better nucleofuge.The alkylation reaction sequence has two advantages for the synthesis of 1: (1) the mildness of the reaction conditions and (2) the wide variety of acyl and alkyl groups that can be incorporated into the product through the (acyloxy)alkyl α-halides.
- Bodor, Nicholas,Sloan, Kenneth B.,Kaminski, James J.,Shih, Chung,Pogany, Stefano
-
p. 5280 - 5284
(2007/10/02)
-
- tert-Butoxycarbanyl as a convenient protecting group in synthesis of potential centrally active dopamine derivatives.
-
Several pivaloyl and pivaloyloxy esters and amides of dopamine were synthesized for possible antiparkinson activity. The compounds were synthesized by select O- and N-acylation and N-methylation procedures. The tert-butoxycarbonyl function is an effective and easily removed nitrogen-protecting group for dopamine. Preliminary biological testing results showed that all compounds tested elicited a hypothermic response in mice, while only O,O-dipivaloyl-N,N-dimethyldopamine reversed reserpine-induced motor depression in mice. However, it is difficult to conclude from the preliminary data that the observed biological effects were due to central dopaminergic receptor stimulation.
- Walker,Ayres,Block,Lock
-
p. 558 - 559
(2007/10/06)
-