- N-Heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid a novel scaffold for the design of uncompetitive α-glucosidase inhibitors
-
Abstract The enzyme α-glucosidase has attracted interest owing to its involvement in the digestive process of carbohydrate, its role in intracellular glycoprotein trafficking, tumorigenesis and viral infection. In this study, several members of a new family of N-heteroarylmethyl substituted azasugars were synthesized and evaluated as α-glucosidase inhibitors. We systematically investigated the effect of different N-substituents as well as the role of hydroxyl and carboxylate moieties on the piperidine ring. The compounds N-heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid emerged as potent α-glucosidase inhibitors. Unlike Acarbose and other clinically relevant α-glucosidase inhibitors, these compounds act through a reversible uncompetitive mechanism of inhibition which make them attractive candidates for drug development.
- Long, Sha,Stefani, Francesca Romana,Biondi, Stefano,Ghiselli, Giancarlo,Panunzio, Mauro
-
p. 5811 - 5822
(2013/09/12)
-
- Beta-sulfonamide hydroxamic acid inhibitors of tace/matrix metalloproteinase
-
This invention provides compounds of Formula I, having the structure: that are useful in treating diseases or disorders mediated by TNF-α, such as arthritis (rheumatoid arthritis (RA), juvenile RA, psoriatic arthritis, osteoarthritis etc), tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection, ankylosing spondylitis, psoriasis, sepsis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, asthma, idiopathic pulmonary fibrosis, vasculitis, systemic lupus erythematosus, irritable bowel syndrome, acute coronary syndrome, hepatitis C, cachexia, COPD, stroke or type 2 diabetes, and for alleviation of symptoms thereof. The invention further provides methods for use of the compounds.
- -
-
Page/Page column 38-39
(2008/06/13)
-
- A General, Selective, High-Yield N-Demethylation Procedure for Tertiary Amines by Solid Reagents in a Convenient Column Chromatography-like Setup
-
(Equation presented) A traditional preparative chromatographic column can be used to achieve quantitative N-demethylation of tertiary N-methylamines and alkaloids. The filling is the crucial part and is loaded with different solid reagents in three reaction zones. The parent compound is charged on the column, and the neat N-demethylated secondary amine leaves the column some minutes later.
- Rosenau, Thomas,Hofinger, Andreas,Potthast, Antje,Kosma, Paul
-
p. 541 - 544
(2007/10/03)
-
- A New Reagent for the Selective, High-Yield N-Dealkylation of Tertiary Amines: Improved Syntheses of Naltrexone and Nalbuphine
-
Secondary amine hydrochlorides are obtained in high yield by reaction of tertiary amines with α-chloroethyl chloroformate followed by warming the intermediate carbamate in methanol.
- Olofson, R. A.,Martz, Jonathan T.,Senet, Jean-Pierre,Piteau, Marc,Malfroot, Thierry
-
p. 2081 - 2082
(2007/10/02)
-