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1.
Borbas KE Chandrashaker V Muthiah C Kee HL Holten D Lindsey JS 《The Journal of organic chemistry》2008,73(8):3145-3158
The use of chlorins as photosensitizers or fluorophores in a range of biological applications requires facile provisions for imparting high water solubility. Two free base chlorins have been prepared wherein each chlorin bears a geminal dimethyl group in the reduced ring and a water-solubilizing unit at the chlorin 10-position. In one design (FbC1-PO3H2), the water-solubilizing unit is a 1,5-diphosphonopent-3-yl ("swallowtail") unit, which has previously been used to good effect with porphyrins. In the other design (FbC2-PO3H2), the water-solubilizing unit is a 2,6-bis(phosphonomethoxy)phenyl unit. Two complementary routes were developed for preparing FbC2-PO3H2 that entail introduction of the protected phosphonate moieties either in the Eastern-half precursor to the chlorin or by derivatization of an intact chlorin. Water-solubilization is achieved in the last step of each synthesis upon removal of the phosphonate protecting groups. The chlorins FbC1-PO3H2 and FbC2-PO3H2 are highly water-soluble (>10 mM) as shown by 1H NMR spectroscopy (D2O) and UV-vis absorption spectroscopy. The photophysical properties of the water-soluble chlorins in phosphate-buffered saline solution (pH 7.4) at room temperature were investigated using static and time-resolved absorption and fluorescence spectroscopic techniques. Each chlorin exhibits dominant absorption bands in the blue and the red region (lambda = 398, 626 nm), a modest fluorescence yield (Phi f approximately 0.11), a long singlet excited-state lifetime (tau = 7.5 ns), and a high yield of intersystem crossing to give the triplet state (Phi isc = 0.9). The properties of the water-soluble chlorins in aqueous media are comparable to those of hydrophobic chlorins in toluene. The high aqueous solubility combined with the attractive photophysical properties make these compounds suitable for a wide range of biomedical applications. 相似文献
2.
Biotinylated peptides often have low solubility in water. In this Letter, we describe a new method to synthesize a biotinylating reagent for water-solubilizing hydrophobic peptides. The biotinyl-6-aminohexanoic derivatives prepared contain a hydrophilic 3,6,9-trioxaundecanedioic acid linker moiety between the biotin and the peptide to improve the water solubility, and also to function as a spacer. The monoesterified derivative of 3,6,9-trioxaundecanedioic acid was synthesized, and the Fmoc-protected ethylenediamine was used to link to the carboxylic group of biotin. The hydrophilic nature of this new biotin-peptide conjugate was also demonstrated in a comparative analysis of compounds containing a biotinyl-6-aminohexanoic acid or 3,6,9-trioxaundecanedioic acid derivative. 相似文献
3.
4.
[formula: see text] A tight-binding, hydrophobic inhibitor of carbonic anhydrase II has been masked with a water-solubilizing, photolabile group derived from o-nitrophenylglycine. This caged inhibitor represents our first effort at the site-specific delivery of prodrugs that can be activated by light. Via this approach, we have begun to address the problems of water insolubility and systemic side effects on administration of tight-binding inhibitors of carbonic anhydrase. 相似文献
5.
A convergent synthesis of a water-soluble cavitand bearing four triazole-linked guanosines was achieved. The critical coupling reaction entailed a copper-catalysed azide-alkyne cycloaddition between 5′-azido-5′-deoxyguanosine and a cavitand template functionalized with propargyl ether rim groups and water-solubilizing phosphate pendant groups. 相似文献
6.
Ichikawa T Kitazaki T Matsushita Y Yamada M Hayashi R Yamaguchi M Kiyota Y Okonogi K Itoh K 《Chemical & pharmaceutical bulletin》2001,49(9):1102-1109
1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities. 相似文献
7.
An Efficient Method for the Conjugation of Hydrophilic and Hydrophobic Components by Solid‐Phase‐Assisted Disulfide Ligation 下载免费PDF全文
Kyohei Muguruma Takuya Shirasaka Daichi Akiyama Dr. Kentarou Fukumoto Dr. Akihiro Taguchi Dr. Kentaro Takayama Dr. Atsuhiko Taniguchi Prof. Yoshio Hayashi 《Angewandte Chemie (International ed. in English)》2018,57(8):2170-2173
Chemical conjugation between hydrophilic and hydrophobic components is difficult because of their extremely different solubility. Herein, we report a new versatile method with a solid‐phase‐assisted disulfide ligation to overcome the difficulty of conjugation attributed to solubility. The method involves two steps in a one‐pot process: 1) loading of a hydrophobic molecule onto a resin in an organic solvent, and 2) release of the solid‐supported hydrophobic molecule as a conjugate with a hydrophilic molecule into an aqueous solvent. This strategy allows the use of a suitable solvent system for the substrates in each step. Conjugates of a water‐insoluble drug, plinabulin, with hydrophilic carriers that could not be prepared by solution‐phase reactions were obtained in moderate yields (29–45 %). This strategy is widely applicable to the conjugation of compounds with solubility problems. 相似文献
8.
In this study we synthesized the water-soluble polymeric prodrugs possessing a 4-methylcatechol (4MC) derivative as a side chain by mechanochemical solid-state copolymerization. 1-benzoyl-4-methylcatechol (Bz4MC) was selected as a model compound of 4MC, and its methacryloyl derivative (1) was synthesized. 6-O-methacryloyl-D-galactose (2) was also prepared as a water-soluble monomer. The mechanochemical solid-state copolymerization of 1 and 2 was carried out to obtain the water-soluble polymeric prodrug possessing the Bz4MC as a side chain. The mechanochemical copolymerization of 1 and 2 proceeded to completion, and the polymeric prodrug produced possessed a narrow molecular weight distribution. Three kinds of polymeric prodrugs, whose compositions were different from one another, were hydrolyzed in vitro. The hydrolysis of these polymeric prodrugs proceeded to completion. The rate constants of hydrolysis decreased with increasing the mole fraction of 1 in polymeric prodrug. It was suggested that the rate constant of hydrolysis could be controlled by the composition, the mole fraction of 1 in the polymeric prodrug. 相似文献
9.
Wipf P Lynch SM Powis G Birmingham A Englund EE 《Organic & biomolecular chemistry》2005,3(21):3880-3882
A series of palmarumycin prodrugs and water-soluble analogs has been synthesized and assayed for inhibition of the thioredoxin-thioredoxin reductase system. Increased aqueous solubility led to an improved in vivo activity profile. 相似文献
10.
Lamotrigine (LTG) is an antiepileptic drug used for the prevention of convulsions. Except several known side effects, hepatic
dysfunction is also reported. Hepatotoxic side effects occur due to the dichlorophenyl moiety which develops an abnormally
low level of glutathione. Depletion of glutathione causes oxidative stress and hepatic cell damage. The goal of the present
study was to test the action and side effects of the three compounds synthesised and compared to LTG. Three amide prodrugs
of LTG were synthesised by its reaction with N-acetylamino acids, viz, glycine, glutamic acid, and methionine. Purified synthesised prodrugs were subjected to thin layer
chromatography, melting point, solubility and partition coefficients determination and characterised by UV, FTIR, 1H and 13C NMR spectroscopy. The synthesised prodrugs were subjected to in vitro hydrolysis and to anticonvulsant and hepatotoxic activity
studies. Significant reduction in hepatotoxicity and comparable anticonvulsant activities were obtained in all synthesised
prodrugs as compared to LTG. 相似文献
11.
Toshifumi Satoh Yoshikazu Kitajyo Ryosuke Sakai Atsushi Narumi Kenji Takahashi Harumi Kaga Noriaki Kaneko Toyoji Kakuchi 《Macromolecular Symposia》2009,279(1):145-150
The synthesis of a unimolecular reverse micelle ( 3 ) consisting of hyperbranched D -glucan as the core and L -leucine ethyl ester as the shell was accomplished through the carbamation reaction of the hyperbranched D -glucan ( 1 ) with the N-carbonyl L -leucine ethyl ester ( 2 ) in pyridine at 100 °C. The polymer 3 was soluble in a large variety of organic solvents, such as methanol, acetone, chloroform, and ethyl acetate, and insoluble in water, which remarkably differed from the solubility of 1 . The solubilities of 3 were also changed by the substitution degrees of the L -leucine moiety. The encapsulation ability of 3 toward water-soluble dyes has been investigated. These results indicated that 3 was a unimolecular reverse micelle with an encapsulation ability toward hydrophilic dye molecules. In addition, 3 showed an molecular size-selective encapsulation ability. 相似文献
12.
T Kawaguchi T Hasegawa T Seki K Juni Y Morimoto A Miyakawa M Saneyoshi 《Chemical & pharmaceutical bulletin》1992,40(5):1338-1340
Five ester prodrugs of 2'3'-dideoxyinosine (DDI) were synthesized for the purpose of improving oral bioavailability. The prodrugs, acetate (C2-DDI), octanoate (C8-DDI), stearate (C18-DDI), benzoate (Bz-DDI), and hemisuccinate (Suc-DDI) were proved to quantitatively regenerate their parent drug by enzymatic hydrolysis. Though the chemical stability of the prodrugs under acidic conditions was not improved, their solubility in water was significantly decreased by esterification, except for Suc-DDI. Bioavailability was evaluated by oral administration to rats. Two hydrophobic prodrugs (C8-DDI and Bz-DDI) showed higher absolute bioavailability (23.5% and 31.0%, respectively) than did DDI (15.2%), though that of C2-DDI (11.5%) and Suc-DDI (4.5%) was poor. 相似文献
13.
The permeabilities of several water-soluble drugs through excised hairless rat skin from their aqueous suspensions were investigated by using newly designed two-chamber diffusion cells. Disodium cromoglycate, diclofenac sodium, dopamine hydrochloride, isoproterenol hydrochloride, diltiazem hydrochloride and papaverine hydrochloride were selected as water-soluble drugs. Indomethacin, a lipophilic drug, and deuterium oxide (D2O) were used for comparison. The skin permeability coefficients of these water-soluble drugs were 100--1000 times lower than that of indomethacin. Since these drugs have high solubility in the donor solution (distilled water or lactate buffer), however, the skin permeation rates, which are in general proportional to the product of skin permeability coefficient and solubility of drugs in the drug-donor compartment, were comparable to or higher than that of indomethacin (1.7 micrograms/cm2/h): the skin permeation rate of dopamine hydrochloride (458 micrograms/cm2/h) was about 300 times higher than that of indomethacin. The water-soluble drugs with lower molecular weight and higher solubility in water showed higher skin permeation rates. These results suggest that some water-soluble drugs with low molecular weight and high solubility in water might be good candidates for transdermal drug delivery. 相似文献
14.
Qing Song ZHOU Xue Hua JIANG Jia Rui YU Ke Jia LI West China School of Pharmacy Sichuan University Chengdu 《中国化学快报》2006,17(1)
Scutellarin is the active ingredient extracted from Erigeron breviscapus, a traditional Chinese herbal medicine. Pharmacological study showed that scutellarin could significantly reduce the blood viscosity, improve the blood flow, decrease the vascular re… 相似文献
15.
5-Trimethylammonio-1,3-dioxo-1,3-dihydro-1λ(5)-benzo[d][1,2]iodoxol-1-ol anion (AIBX 1a), an o-iodoxybenzoic acid (IBX) derivative having the trimethylammonium moiety on its phenyl ring, possesses very good solubility in water and distinct oxidative properties from IBX, which is demonstrated in the oxidation of various β-keto esters to the corresponding dehydrogenated products using water as cosolvent. The regeneration of AIBX 1a can be easily realized from the reaction mixture due to its good water solubility. 相似文献
16.
Niu SL Massif C Ulrich G Renard PY Romieu A Ziessel R 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(23):7229-7242
A series of water-soluble red-emitting distyryl-borondipyrromethene (BODIPY) dyes were designed and synthesized by using three complementary approaches aimed at introducing water-solubilizing groups on opposite faces of the fluorescent core to reduce or completely suppress self-aggregation. An additional carboxylic acid functional group was introduced at the pseudo-meso position of the BODIPY scaffold for conjugation to amine-containing biomolecules/biopolymers. The optical properties of these dyes were evaluated under simulated physiological conditions (i.e., phosphate-buffered saline (PBS), pH 7.5) or in pure water. The emission wavelength (λ(max)) of these labels was found in the 640-660 nm range with quantum yields from modest to unprecedentedly high values (4 to 38%). The bioconjugation of these distyryl-BODIPY dyes with bovine serum albumin (BSA) and the monoclonal antibody (mAb) 12A5 was successfully performed under mild aqueous conditions. 相似文献
17.
Dendrimers are macromolecules characterized by high controlled size, shape and architecture, presence of inner cavities able to accommodate small molecules and many peripheral functional groups to bind target entities. They are of eminent interest for biomedical applications, including gene transfection, tissue engineering, imaging, and drug delivery. The well-known pharmacological activities of ursolic and oleanolic acids are limited by their small water solubility, non-specific cell distribution, low bioavailability, poor pharmacokinetics, and their direct administration could result in the release of thrombi. To overcome such problems, in this paper we described their physical incorporation inside amino acids-modified polyester-based dendrimers which made them highly water-soluble. IR, NMR, zeta potential, mean size of particles, buffer capacity and drug release profiles of prepared materials were reported. The achieved water-soluble complexes harmonize a polycationic character and a buffer capacity which presuppose efficient cell penetration and increased residence time with a biodegradable cell respectful scaffold, thus appearing as a promising team of not toxic prodrugs for safe administration of ursolic and oleanolic acids. 相似文献
18.
Indrajit Shown Sudip Banerjee A.V. Ramchandran Kurt E. Geckeler C. N. Murthy 《Macromolecular Symposia》2010,287(1):51-59
Summary: In the present work water-soluble lactose based oligomers of β-cyclodextrin were synthesized by a simple and efficient condensation polymerization process. Proposed water-soluble β-cyclodextrin oligomers were prepared by controlled reaction between β-cyclodextrin and a triazine linker and purification by an ultrafiltration process. Similarly, lactose based β-cyclodextrin oligomers were synthesized for enhanced water solubility. The physical and chemical properties of the synthesized polymers were characterized by FT-IR and 1H NMR spectroscopy, XRD analysis, thermogravimetric analysis (TGA) and aqueous solubility determination.. Molecular weights of these β-cyclodextrin based oligomers were measured by ESI technique. These β-cyclodextrin based water-soluble oligomers polymers were used as supramolecular carriers for efavirenz (an anti HIV drug), improving the inclusion property and aqueous solubility properties of this drug. These synthesized oligomers were found to improve stability and aqueous solubility of efavirenz on their (1:1) inclusion complex through phase solubility and dissolution studies. Reduced cytotoxicity than the parent β-CD was observed in hemolysis test. 相似文献
19.
Nile Red (compound A) fluoresces at about 530 nm with good quantum yields in apolar solvents. In more polar ones its fluorescence emission shows a dramatic, and potentially useful, shift to about 640 nm, but its quantum yield is significantly reduced. Further, Nile Red has a very poor solubility in aqueous media. The hypothesis tested in this paper is that Nile Red derivatives that incorporate water-solubilizing groups will tend to fluoresce with good quantum yields in aqueous media, and in the more useful wavelength range around 640 nm. Thus three Nile Red derivatives, 1-3, were prepared. Compound 1 had three hydroxyl groups more than Nile Red, but was surprisingly insoluble in aqueous media. However, the dicarboxylic acid 2 and carboxylic/sulfonic acid derivative 3 showed excellent water solubilities. Spectral data for 2 and 3 showed that they do indeed fluoresce with good quantum yields in the 640 nm region in aqueous media. These properties of compounds 2 and 3 might be useful in the development of fluorescent probes for biotechnology. 相似文献