Mini Reviews in Medicinal Chemistry - Volume 5, Issue 6, 2005

Cell-surface G protein-coupled receptors (GPCRs) constitute nearly 5% of the human genome, making them the largest superfamily of all receptor proteins. Approximately 300 - 350 of a total of 700 - 1000 GPCRs are the “non-sensory” GPCRs, which represent the main drug targets for the majority of medicines currently available. In particular, the “rhodopsin-like” Class I (Family A) GPCRs are pre-eminent therapeutic targets Read More

The evaluation of allosteric ligands at muscarinic receptors is discussed in terms of the ability of the experimental data to be interpreted by the allosteric ternary complex model. The compilation of useful SAR information of allosteric ligands is not simple, especially for muscarinic receptors, where there are multiple allosteric sites and complex interactions.

Allosteric modulators for adenosine receptors (ARs) are of an increasing interest and may have potential therapeutic advantage over orthosteric ligands. Benzoylthiophene derivatives (including PD 81,723), 2-aminothiazolium salts, and related allosteric modulators of the A1 AR have been studied. The benzoylthiophene derivatives were demonstrated to be selective enhancers for the A1 AR, with little or no effect on other s Read More

Allosteric modulators allow for the fine-tuning of receptor responses to endogenous neurotransmitters and exogenous therapeutic agents. Different types of allosteric modulation of dopamine receptors are discussed as well as the significance of such modulation in the control of normal biological processes and in the treatment of disease.

During the last decade an increasing number of reports describe the roles of active oxygen species in the development or exacerbation of various kinds of diseases. Antioxidants are of great interest because of their involvement in important biological and industrial processes. They have been found to possess anticancer, anti-cardiovascular, anti-inflammatory and many other activities. Many attempts have been made to elucid Read More

The migration of leukocytes from the blood stream to sites of infection is a key event in cellular immune response, mediated by multiple types of molecules including several adhesion receptors. The inhibition of adhesion receptors holds great promise for novel therapeutical strategies to treat chronic inflammatory disorders or autoimmune diseases. This review reports on recent advances in adhesion-based therapeutics and fo Read More

One of the most important stages of the drug discovery process is the generation of lead compounds. Structure-activity relationships (SAR) are well-integrated in modern drug discovery and have been largely used for the finding of new leads, scaffold generation, the optimization of receptor or enzyme affinity, as well as of pharmacokinetic and physicochemical properties. This review highlights some SAR approaches that can Read More

Since the introduction of (+)-tubocurarine into anaesthetic and surgical practice (1942), a number of non-depolarizing neuromuscular blocking agents (NMBs) with improved pharmacological properties have been developed during the last sixty years. However, after withdrawal of rapacuronium from clinical use, there is still a need for an ultra-short acting non-depolarizing muscle relaxant with rapid onset as substit Read More