Current Medicinal Chemistry - Volume 11, Issue 24, 2004

The discovery of the two isoenzymes COX-1 and COX-2 and the knowledge of their function, localisation and regulation has initiated the development of COX-2 selective inhibitors (coxibs). Inducible COX-2 at the peripheral site of inflammation has been detected in the early 1990s, the involvement of recently detected spinal COX-2 has led to new insights into mechanisms of pain and may explain analgesic and antipyreti Read More

Synthetic ether-linked analogues of phosphatidylcholine and lysophosphatidylcholine, collectively named as antitumour lipids (ATLs), were initially synthesized in the late 60s, but have attracted a renewed interest since the finding that the ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3- phosphocholine (ET-18-OCH3, edelfosine), a synthetic analogue of 2-lysophosphatidylcholine considered the ATL prototype, induces a sel Read More

This review gives a brief overview of the expression patterns, molecular pharmacology and physiological roles of the vanilloid receptor 1 (VR1). Particular emphasis is given to the therapeutic utility of VR1 modulators. Small molecule agonists of VR1, including capsaicin and RTX, are currently utilized for a number of clinical syndromes, including intractable neuropathic pain, spinal detrusor hyperreflexia, and bladder hypersensi Read More

The cellular and molecular mechanisms underlying cardiovascular dysfunctions are widely unknown. Basically, pathological changes in the cardiovascular system arise from protein alterations. Proteomics comprises a set of tools for the large-scale study of gene expression at the protein level thereby allowing for the identification of protein alterations responsible for the development and the pathological outcome Read More

The cellular mechanism of action of tedisamil (KC-8857) (TED), a novel antiarrhythmic / antifibrillatory compound, was studied on transmembrane currents in guinea pig, rabbit and dog ventricular myocytes by applying the patch-clamp and the conventional microelectrode technique. In guinea pig myocytes the rapid component of the delayed rectifier potassium current (IKr) was largely diminished by 1 μM TED (from 0.88±0.17 Read More

In recent years several mutations and sequence polymorphisms of the glucocorticoid receptor gene have been described. The majority of mutations have been found in patients with a rare endocrinological abnormality, the glucocorticoid resistance syndrome. In addition, some sequence polymorphisms have been considered to contribute to various diseases, but unambiguous correlations have not been establis Read More

The scope of this review encompasses the importance of furocoumarins and the most important developments in this field that have been made in recent years, with particular emphasis placed on the aspects related to medicinal chemistry. A concise and exhaustive overview is given regarding the methods used for the synthesis of these compounds, new furocoumarins isolated from natural sources, and the most significant biol Read More

The replacement of peptide bond is an important segment in the synthesis of peptidomimetics, because this modification may result in the preparation of biologically active analogues with improved properties, especially regarding bioavailability and metabolical stability. The introduction of sulfonamide group increases polarity of a molecule and the hydrogen-bond donor properties as a sulfonamide N-H is more acidic (pK Read More