51-59-2Relevant academic research and scientific papers
Scalable synthesis of 8-amino-3-hydroxy-6 H -benzo[ c ]chromen-6-one: Key intermediate for SEGRA via the Hurtley reaction
Kudo, Kazuhiro,Yamamoto, Noriyoshi
, p. 309 - 314 (2015)
A practical and scalable process for the preparation of 8-amino-3-hydroxy-6H-benzo[c]chromen-6-one in multihundred kilogram amounts has been developed. The key features of this synthesis are the application of the Hurtley reaction with a copper and base combination and the development of a purification process. The new synthesis improved the total yield from 49.0% to 59.5% and reduced the number of steps from three to two. Compared with the conventional medicinal route, manufacturing costs were reduced significantly by the use of inexpensive, easy to procure materials.
A Polymeric Drug for Treatment of Inflammatory Bowel Disease
Brown, Joseph P.,McGarraugh, Geoff V.,Parkinson, Thomas M.,Wingard, Robert E.,Onderdonk, Andrew B.
, p. 1300 - 1307 (1983)
Sulfasalazine (SASP) consists of salicylic acid azo linked at the 5-position to a pyridine-containing sulfonamide.This drug, currently used in inflammatory bowel disease treatment, is reductively cleaved by anaerobic bacteria in the lower bowel to 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP).Recent reports indicate that 5-ASA is the active therapeutic moiety and that SP is responsible for a variety of adverse clinical side effects.Water-soluble polymer 7, which contains salicylate residues azo linked at the 5-position to an inert polymer backbone, has been synthesized for the side-specific reductive release of 5-ASA in the lower bowel.Preparations of 7 deliver (chemical reduction) >1.96 mmol of 5-ASA/g of polymer.In vitro studies with the polymer in anaerobic rat cecal bacteria demonstrated a reduction rate of approximately 1 μequiv of azo bond h-1 (mL of cecal content)-1.A pharmacokinetic comparison of polymer and SASP showed similar deliveries of 5-ASA and metabolites to the lower bowel, blood and urine of orally dosed rats.Polymer 7 proved more active than SASP or 5-ASA in the guinea pigs ulcerative colitis model.Potential therapeutic advantages of 7 include nonabsorption/nonmetabolism in the small intestine, direct 5-ASA release at the disease site, and nonabsorption/nonmetabolism of the reduction-released carrier polymer.
Liposomal formulations of inflammatory bowel disease drugs: Local versus systemic drug delivery in a rat model
Kesisoglou, Filippos,Zhou, Simon Yuji,Niemiec, Susan,Lee, Jordan Wing,Zimmermann, Ellen M.,Fleisher, David
, p. 1320 - 1330 (2005)
Purpose. Based on adherence to intestinal mucosa, intralumenally administered liposomal formulations of 5-aminosalicylate (5-ASA) and 6-mercaptopurine (6-MP) were studied for their potential to enhance local drug delivery to intestinal tissue for the treatment of inflammatory bowel disease. Methods. 5-ASA was encapsulated in standard phospholipid liposomes while 6-MP required encapsulation in nonphospholipid liposomes to obtain equivalent drug loading. Encapsulation efficiency was measured by size-exclusion chromatography/high-performance liquid chromatogtaphy (HPLC). Liposomal formulations or solution of the drugs were injected into unligated jejunum to compare pharmacokinetics and into ligated loops of rat ileum and colon to evaluate local delivery. Dextran sulfate and acetic acid induced colitis were used as models of lower intestinal inflammation. Plasma, tissue and luminal drug and metabolite levels were measured by liquid scintillation counting or HPLC. Results. Encapsulation efficiency of 6-MP was dependent on lipid content and composition. While liposomal encapsulation significantly reduced systemic absorption of 5-ASA this was not the case for 6-MP. Liposomal adherence to intestinal tissue resulted in increased tissue levels for 5-ASA; however, 6-MP local tissue levels were not improved compared to solution drug. Conclusions. Nonphospholipid liposomes optimize encapsulation of 6-MP. While liposomal formulations show potential for local drug delivery to diseased bowel, drug physicochemical properties, absorption, and metabolic profiles dictate tissue-targeting potential. Liposomes reduce systemic availability from paracellular absorption of hydrophilic 5-ASA, but fail to improve local tissue delivery of 6-MP, a molecule absorbed by passive membrane permeation that undergoes extensive first- pass metabolism.
Synthesis and in vitro bioactivity evaluation of new glucose and xylitol ester derivatives of 5-aminosalicylic acid
Yousefi, Samira,Bayat, Saadi,Abdul Rahman, Mohd Basyaruddin,Ismail, Intan Safinar,Saki, Elnaz,Abdulmalek, Emilia
, p. 97295 - 97307 (2015)
New glucose and xylitol esters of 5-amino salicylic acid (5-ASA) were synthesized followed by evaluation of their in vitro antimicrobial, anti-cancer and anti-inflammatory activities. The results of the antimicrobial activity assessment revealed that the new final esters were more effective against Gram-negative as well as Gram-positive bacteria than the original drug. Furthermore, the new final products were confirmed by a cytotoxicity assay over HT-29 and 3T3 cell lines to be less toxic for normal cells compared to the initial drug. On the other hand, however, their suppressive effect against cancerous cells was somewhat lower. Meanwhile, the anti-inflammatory activity assay over a RAW264.7 macrophage cell line demonstrated that the NO inhibition activity of the conjugated drug to the previously mentioned saccharides, especially to glucose, has slightly improved compared to the non-conjugated drug. Finally, in silico screening was also performed in order to predict the potential interactions and binding energy of the novel products against cyclooxygenase (COX-1/COX-2) and lipoxygenase (5-LOX) proteins. Findings indicated that the new products had greater hydrogen bonds and binding affinities with the active sites of proteins towards 5-ASA.
Synthesis and in?vitro Bioactivity Evaluation of New Galactose and Fructose Ester Derivatives of 5-Aminosalicylic Acid
Yousefi, Samira,Bayat, Saadi,Rahman, Mohd Basyaruddin Abdul,Ibrahim, Zalikha,Abdulmalek, Emilia
, (2017/04/18)
Inflammatory bowel disease (IBD) is the main risk factor for developing colorectal cancer which is common in patients of all ages. 5-Aminosalicylic acid (5-ASA), structurally related to the salicylates, is highly active in the treatment of IBD with minor side effects. In this study, the synthesis of galactose and fructose esters of 5-ASA was planned to evaluate the role of glycoconjugation on the bioactivity of the parent drug. The antibacterial activity of the new compounds were evaluated against two Gram-negative and two Gram-positive species of bacteria, with a notable effect observed against Staphylococcus aureus and Escherichia coli in comparisons with the 5-ASA. Cytotoxicity testing over HT-29 and 3T3 cell lines indicated that the toxicity of the new products against normal cells was significantly reduced compared with the original drug, whereas their activity against cancerous cells was slightly decreased. The anti-inflammatory activity test in RAW264.7 macrophage cells indicated that the inhibition of nitric oxide by both of the monosaccharide conjugated derivatives was slightly improved in comparison with the non-conjugated drug.
The antioxidant properties of salicylate derivatives: A possible new mechanism of anti-inflammatory activity
Borges, Rosivaldo S.,Castle, Steven L.
supporting information, p. 4808 - 4811 (2015/10/28)
The synthesis and antioxidant evaluation by DPPH scavenging of a series of salicylic acid derivatives is described. Gentisic acid and its ester, amide, and amino analogs possess more radical scavenging capacity than salicylic acid and other salicylate derivatives. This property can possibly provide an additional pathway for anti-inflammatory activity through either single electron or hydrogen atom transfer, leading to a new strategy for the design of anti-inflammatory agents.
Preparation and characterization of multi-walled carbon nanotubes (MWCNTs), functionalized with phosphonic acid (MWCNTs-C-PO3H2) and its application as a novel, efficient, heterogeneous, highly selective and reusable catalyst for acetylation of alcohols, phenols, aromatic amines, and thiols
Dehghani, Farzaneh,Sardarian, Ali Reza,Doroodmand, Mohammad Mehdi
, p. 673 - 684 (2014/05/20)
A novel, efficient, heterogeneous, and reusable multi-walled carbon nanotubes (MWCNTs), functionalized with phosphonic acid (MWCNTs-C-PO 3H2) has been synthesized. The synthesized CNTs were characterized using some electron microscopic techniques such as scanning electron microscopy (SEM), atomic force microscopy (AFM), Energy dispersive X-ray spectroscopy (EDAX), and also some thermal and spectroscopic methods such as thermogravimetry (TG). The nitrogen adsorption behavior of the MWCNTs-C-PO3H2 catalyst was evaluated using the TG instrumentation system at 25°C. The catalyst was applied successfully for highly efficient and selective acetylation of alcohols, phenols, thiols and aromatic amines with acetic anhydride at room temperature under solvent-free conditions. The reusability of the catalyst was checked and the recovered catalyst was reused for five runs without significant loss in activity.
Iron-doped single-walled carbon nanotubes as new heterogeneous and highly efficient catalyst for acylation of alcohols, phenols, carboxylic acids and amines under solvent-free conditions
Sharghi, Hashem,Jokar, Mahboubeh,Doroodmand, Mohammad Mahdi
experimental part, p. 426 - 442 (2011/04/15)
Iron-doped single-walled carbon nanotubes (Fe/SWCNTs) represent an efficient and new heterogeneous reusable catalyst for the acylation of a variety of alcohols, phenols, carboxylic acids and amines with acid chlorides or acid anhydrides under solvent-free conditions. The reactions of various primary, secondary, tertiary, and benzylic alcohols, diols, phenols, as well as aromatic and aliphatic amines give acylated adducts in good to excellent yields.
Synthesis and characterization of metabolites and potential impurities of balsalazide disodium, an anti-inflammatory drug
Khan, Md. Umar,Baseer,Kumar, S. Ranjith,Saravanakumar,Prasannanjali,Gupta, P. Badarinadh,Kaushik, Vipin K.,Handa, Vijay K.,Islam, Aminul
experimental part, p. 2241 - 2253 (2010/10/02)
Balsalazide disodium (Colazide) is an oral prodrug of mesalamine (5-aminosalicylic acid) and possesses anti-inflammatory properties. During the process development for balsalazide disodium, we observed eight impurities, namely des-alanine balsalazide, balsalazide-alanine, balsalazide 3-isomer, decarboxy balsalazide, bis-azo salicylic acid, biphenyl-azo salicylic acid, bis-azo diacid, and bis-azo triacid. The present work describes the synthesis and characterization of these impurities. Copyrigh
Bisacetamide hydrochloride: A chemoselective and inexpensive N-acetylating reagent for aminophenols
Peng, Yanqing,Song, Gonghua,Ding, Fang
, p. 2021 - 2023 (2007/10/03)
A facile and chemoselective acetylation of aminophenols using bisacetamide hydrochloride under conventional heating and microwave irradiation has been developed. Also, a rapid method for the microwave-assisted preparation of aminophenols is described herein.
