Mini Reviews in Medicinal Chemistry - Volume 2, Issue 3, 2002

5-Aryl-pyrrolo[2,3-d]pyrimidines incorporating different N7-substituents have been prepared and evaluated for their inhibitory potency towards the tyrosine kinase c-Src. Optimization of these compounds resulted in highly potent c-Src inhibitors, some (e.g. 4g, 6g, 7h, 8l ) with excellent specificity towards other receptor and nonreceptor tyrosine kinases. In addition compounds 4g, 5b and 5c are characterized by a good pharmacok Read More

Ecadotril and dexecadotril are powerful and selective inhibitors of neprilysin (NEP, EC 3.4.24.11) and are being developed as therapeutic agents, since they behave as prodrugs of the enantiomers of thiorphan. They exhibit different pharmaceutical profiles (intestinal antisecretatory action for the (R) enantiomer, i.e. dexecadotril, and cardiovascular activity for the (S) enantiomer, i.e. ecadotril). Fasidotril is a related compound Read More

Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogues against different viral diseases. The basic idea is to achieve nucleotide delivery into cells bypassing limitations encountered during the intracellular formation of nucleotides. The cycloSal-concept is one of several pronucleotide systems reported so far. For some nucleoside analogues, the cycloSal-approach improv Read More

Cross-resistance development against most peptidic HIV-1 protease inhibitors (PI) forces the development of nonpeptidic alternatives. The classes of nonpeptidic protease inhibitors was limited so far to cyclic ureas and 4-hydroxy-2-pyrones with problems of limited bioavailability by extensive metabolism and protein binding. Cage dimeric 4-aryl-1,4-dihydropyridines have been developed as third class of nonpeptidic PIs. In the f Read More

The involvement of the 20S proteasome in the degradation of critical intracellular regulatory proteins has suggested the potential use of proteasome inhibitors as novel anti-inflammatory agents and for the treatment of cancer and auto-immune diseases. Early inhibitors of the 20S proteasome were relatively nonspecific compounds and used for in vitro studies of the ubiquitin / proteasome-dependent degradation p Read More

Retinoids play a crucial role in cellular differentiation and proliferation of epithelial tissue and their utility in oncology and dermatology is well documented. This mini review focuses on the role of all-trans-retinoic acid (ATRA or RA), the principal endogenous retinoid and its metabolism in cancer therapy.ATRA has been used successfully in differentiating therapy of acute promyelecytic leukemia and other types of cancers. Read More

Not only a high level of low-density lipoprotein (LDL) cholesterol, but also a low level of highdensity lipoprotein (HDL) cholesterol, is a critical risk factor for atherosclerosis and coronary heart disease. Although fibrates and niacin can be used to improve low HDL cholesterol levels, their effect is not wholly satisfactory, so better drugs for the elevation of HDL cholesterol are desired. Among the many methods that may be used to Read More

Retinoids are a group of synthetic compounds designed to refine the numerous biological activities of retinoic acid into pharmaceuticals for several diseases, including cancer. Designs that conformationallyrestricted the rotation of the structures resulted in arotinoids that were biologically active, but with increased toxicity. Incorporation of a heteroatom in one cyclic ring of the arotinoid structures drastically reduced the toxicity, w Read More

Ecdysteroids are known insect moulting hormones, regulating the insects'metamorphosis. At the same time, ecdysteroids reveal beneficial effects on humans and animals alike. Medicinal plants have been subjected to an intensive research, addressing the presence of ecdysteroids. The possible utilization of medicinal plant deals with their use as raw materials for health preparations and also for the isolation of new phytoecdyster Read More