Search results for "Carboxylic acid"
showing 10 items of 460 documents
Statins and the squalene synthase inhibitor zaragozic acid stimulate the non-amyloidogenic pathway of amyloid-beta protein precursor processing by su…
2010
Cholesterol-lowering drugs such as statins influence the proteolytic processing of the amyloid-beta protein precursor (AbetaPP) and are reported to stimulate the activity of alpha-secretase, the major preventive secretase of Alzheimer's disease. Statins can increase the alpha-secretase activity by their cholesterol-lowering properties as well as by impairment of isoprenoids synthesis. In the present study, we elucidate the contribution of these pathways in alpha-secretase activation. We demonstrate that zaragozic acid, a potent inhibitor of squalene synthase which blocks cholesterol synthesis but allows synthesis of isoprenoids, also stimulates alpha-secretase activity. Treatment of human n…
Clinical evaluation of bempedoic acid for the treatment of hyperlipidaemia.
2021
Bempedoic acid (BA) is a novel first-in-class oral lipid-lowering therapy. BA has been approved by the European Medicinal Agency and Food and Drug Administration and has been commercialised throughout Europe since the end of 2020 as an add-on therapy in patients at high/very-high cardiovascular risk that are not at LDL-C goals with current lipid-lowering treatments. Recently, Italian lipid management experts gathered to discuss several open questions on BA characteristics and BArelated practical clinical issues. The panel permitted collection of its opinions in a ten Q&A format. Aim: The aim of this viewpoint is to discuss and answer several open questions on BA characteristics and BA-r…
Six-Step Gram Scale Synthesis of the HIV Integrase Inhibitor Dolutegravir Sodium
2021
A short and practical synthesis for preparing the active pharmaceutical ingredient dolutegravir sodium was investigated. The convergent strategy developed herein starts from 3-(R)-amino-1- butanol and builds up the BC ring system in 76% isolated yield over four steps. Ring A was constructed by a one-pot 1,4-addition to diethyl-(2E/Z)-2-(ethoxymethylidene)-3-oxobutandioate and subsequent MgBr2·OEt2-mediated regioselective cyclization. Amide formation with 2,4- difluorobenzylamine was either performed from the carboxylic acid or through aminolysis of the corresponding ester precursor. Final salt formation afforded dolutegravir sodium in 48–51% isolated yield (HPLC-purity: 99.7–99.9%) over six…
An efficient esterification of pullulan using carboxylic acid anhydrides activated with iodine
2010
Received August 9, 2009Accepted January 12, 2010Published online February 11, 2010Acylation of alcohols (esterification) with anhydride is an important and routinely utilizedtransformation in organic synthesis. Iodine is a cheap and one of the most powerful anhy-dride activating agents for the esterification of alcohols. Therefore, an efficient and cost ef-fective method was developed for the acylation of pullulan polysaccharide by using differentacid anhydrides activated with iodine. A series of organo-soluble pullulan esters were suc-cessfully synthesized, purified and characterized. Under solvent free conditions, it was feasi-ble to fabricate pullulan nonaacetate and pullulan stearate. A…
Use of gabapentin to reduce chronic neuropathic pain in Fabry disease.
2003
The effect of the anticonvulsant gabapentin on neuropathic pain was studied in six male patients with Fabry disease, aged 15-45 years. After 4 weeks of treatment, pain, as measured using the Brief Pain Inventory, was decreased compared with baseline. Treatment was generally well tolerated. This study indicates that gabapentin should be considered as a treatment option for the neuropathic pain of Fabry disease.
A comparison of the effectiveness of azelaic and pyruvic acid peels in the treatment of female adult acne: a randomized controlled trial
2020
AbstractChemical peels are widely used as therapeutic agents in dermatology and cosmetology. This study aims to explore the differences in the effectiveness of azelaic and pyruvic acid peels in the treatment of acne vulgaris. Eligibility criteria for participants were: female gender, 18–25 years of age, no dermatological treatment within the last 12 months and mild to moderate papulopustular acne. We treated 120 young women (with a mean age of 22 years old) with six peeling sessions at 2-week intervals. In the parallel clinical study design, one randomized group (n = 60, 50%) was treated using azelaic acid (AA), whereas the second group participated in pyruvic acid (PA) sessions. We evaluat…
C4-dicarboxylate carriers and sensors in bacteria
2002
AbstractBacteria contain secondary carriers for the uptake, exchange or efflux of C4-dicarboxylates. In aerobic bacteria, dicarboxylate transport (Dct)A carriers catalyze uptake of C4-dicarboxylates in a H+- or Na+-C4-dicarboxylate symport. Carriers of the dicarboxylate uptake (Dcu)AB family are used for electroneutral fumarate:succinate antiport which is required in anaerobic fumarate respiration. The DcuC carriers apparently function in succinate efflux during fermentation. The tripartite ATP-independent periplasmic (TRAP) transporter carriers are secondary uptake carriers requiring a periplasmic solute binding protein. For heterologous exchange of C4-dicarboxylates with other carboxylic …
Identification of organic hydroperoxides and hydroperoxy acids in secondary organic aerosol formed during the ozonolysis of different monoterpenes an…
2009
On-line ion trap mass spectrometry (ITMS) enables the real-time characterization of reaction products of secondary organic aerosol (SOA). The analysis was conducted by directly introducing the aerosol particles into the ion source. Positive-ion chemical ionization at atmospheric pressure (APCI(+)) ITMS was used for the characterization of constituents of biogenic SOA produced in reaction-chamber experiments. APCI in the positive-ion mode usually enables the detection of [M+H](+) ions of the individual SOA components. In this paper the identification of organic peroxides from biogenic volatile organic compounds (VOCs) by on-line APCI-ITMS is presented. Organic peroxides containing a hydroper…
Activation of phospholipases C and D by the novel metabotropic glutamate receptor agonist tADA.
1997
Abstract In hippocampal slices taken from 8-day-old rats, trans-azetidine-2,4-dicarboxylic acid (tADA), a novel glutamatergic agonist acting preferentially at class I mGluR receptors, activates phosphoinositide and phosphatidylcholine hydrolysis with widely different potencies. Inositol phosphate formation was maximally increased at 10 μM tADA ( ec 50: 1.2 μM), while phospholipase D activation was observed at a tADA concentration of 1 mM. This is the first report of a tADA-induced phospholipase D activity. © 1997 Elsevier Science Ltd. All rights reserved.
Stereocontrolled synthesis of D-α-hydroxy carboxylic acid from L-amino acids
1987
Abstract Optically active D-α-hydroxy carboxylic acids are obtained from L-amino acids via L-α-halocarboxylic acids and their stereoselective reaction with cesium p-nitrobenzoate.