Synthetic medicinal chemistry

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Synthetic Medicinal Chemistry Aventis Pharma Deutschland Industriepark Hoechst 65926 Frankfurt am Main Germany... 

One of the goals of synthetic medicinal chemistry is to design potent inilibitors of clinically important proteases. Elastase inhibitors may be useful for treatment of emphysema, pancreatitis, and arthritis,a/b while inhibitors of the angiotensinogen-converting enzyme or of renin (Box 22-D) can help control blood pressure. Inhibition of thrombin, factor Xa, or other blood clotting factors (Fig. 12-17) may prevent blood clots and inhibition of the cytosolic tryptase may provide a new treatment for asthma. Inhibition of the cysteine protease cathepsin K may help combat osteoporosis and inhibition of cysteine proteases of corona viruses may fight the common cold. Cysteine proteases of schistosomes are also targets for protease inhibitors.c... 

Absorption - Much of the effort in synthetic medicinal chemistry involves attempts to confer oral activity to parenterally active drugs. Lack of oral activity due to inadequate concentrations in the systemic circulation... 

Synthetic medicinal chemistry can remain one of the major cornerstones to drug discovery since it is the very structure of a new drug which will ultimately determine its success in human therapy. Yet the optimum structure of a novel therapeutic agent must reflect the input from many allied disciplines besides organic chemistry. 

A large number of target-drug-molecules invariably contain cyclic skeletons that could be either aromatic or heterocyclic in nature. Therefore, such specific reactions that help in the formation cyclic structures play a vital role in synthetic medicinal chemistry. These ringforming reactions are usually referred to as annelation reactions. 

Enzymes, so often popular for explaining the mechanism of drug action and detoxification, form the subject matter of chapter 3. The present state of knowledge of the relationship of chemical structure of polycyclic hydrocarbons to the likelihood of carcinogenicity is reviewed in chapter 4. The recently developed application of free energy calculations to the action of chemicals on biological systems often leaves the average medicinal chemist bewildered, and chapter 5 aims to introduce and explain the physical chemical concepts involved so that the reader who is interested may be better equipped to read the specialised reviews which are available. In the last chapter, a very active facet of synthetic medicinal chemistry — the synthesis of nitriles - is reviewed. 

Fulvio Gualtieri. New Trends in Synthetic Medicinal Chemistry. New York Wiley-VCH 2000 98. 

In the early 1990s, combinatorial chemistry was a highly speculative and competitive arena. It is now beyond the proof of concept stage, and some people estimate that 50% of synthetic medicinal chemistry will be combinatorial by the year 2002. The interest in this field has been such that whole industries have grown up around it, for example, in synthesizers, resins, and special conferences and journals. It has also led to many research projects in polymer chemistry, in newer analytical chemistry techniques, and in computational chemistry. It is a field in which a chapter in an encyclopedia is, unfortunately, likely to become outdated very quickly. 

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