Approach medicinal chemistry

Perspectives of the cholinergic approach Anticholinesterases M/muscarinic agonists Nicotinic agents Glutamatergic approach Medicinal chemistry... 

Chemometrics. Statistics and Computer Application in Analytical Chemistry. New York, Wiley-VCH. yer D C and P D J Grootenhuis 1999. Recent Developments in Molecular Diversity nputational Approaches to Combinatorial Chemistry. Annual Reports in Medicinal Chemistry 187-296,... 

J S, I Morize, P R Menard, D L Cheney, C Hulme and R F Labaudiniere 1999. New 4-Point irmacophore Method for Molecular Similarity and Diversity Applications Overview of the thod and Applications, Including a Novel Approach to the Design of Combinatorial iraries Containing Privileged Substructures. Journal of Medicinal Chemistry 42 3251-3264. 

Sheridan R P, R Ndakantan, J S Dixon and R Venkataraghavan 1986. The Ensemble Approach to Distanc Geometry Application to the Nicotinic Pharmacophore. Journal of Medicinal Chemistry 29 899-906. 

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. 

Both approaches outlined deliver information that is best used in cycles of medicinal chemistry/computer aided drug design in order to refine the compounds. 

Medicinal Chemistry Approaches and the Role of Quantitative Structure... 

Kubinyi H. QSAR Hanch analysis and related approaches. In Mannhold R, Krogsgaard-Larsen P, Timmerman H, editors, Methods and principles in medicinal chemistry, Vol. 1. Weinheim VCH, 1993. 

In this review, general and efficient approaches to a diverse series of triazoles and coumarin derivatives have been developed and discussed. The obtained products have been characterized with the help of spectroscopic techniques and were screened for their antiviral and antitumor activity. The methods could provide valuable routes to various coumarin derivatives and enrich the organic and medicinal chemistry of coumarins. The synthesized triazoles and coumarin derivatives showed moderate to good antiviral and antitiunor activities. 

Kerns, E. H., Di, L. Physicochemical profiling overview of the screens. Drug Discov. Today Technol. 2004, 1, 343-348. Van de Waterbeemd, H. Physicochemical approaches to drug absorption. In Drug Eioavailability (Methods and Principles in Medicinal Chemistry), Van de Waterbeemd, H., Lennernas, H., Artursson, P. (eds.), Wiley-VGH, Weinheim, 2003, pp. 3-20. 

Of course, class 4 is not valuable in medicinal chemistry. Such compounds have to be excluded from drug discovery processes as early as possible. At present, there are computer alert programs based on the Rule-of-5 or similar approaches that are used in preliminary screening to select and exclude compounds of class 4 [71]. Van de Waterbeemd indicated in 1998 that the four BCS classes of drugs can be determined solely by considering physicochemical descriptors such as molecular weight and PSA [72]. However, as mentioned in this chapter, those descriptors are too crude for the quantitative description of molecular size and H-bonding ability. 

Ghose, A. K., Crippen, G. M. The distance geometry approach to modeling receptor sites In Comprehensive Medicinal Chemistry. The Rational Design, Mechanistic Study and Therapeutic Application of Chemical Compounds, Hansch, C.,... 

This is already the 37th volume in our series on Methods and Principles in Medicinal Chemistry which started in 1993 with a volume on QSAR Hansch Analysis and Related Approaches, written by Hugo Kubinyi. An average release of roughly three volumes per year indicates the increasing appreciation of the series in the MedChem world. 1 want to express my sincere thanks to my editor friends Hugo Kubinyi and Gerd Folkers for their continuous and precious contributions to the steady development of our series. 

The hepatitis C virus (HCV) is responsible for a world-wide epidemic with approximately 170 million people infected. It was identified only in the 1980s and since that time great efforts have been made in the search for treatments. Genetic analysis of the virus revealed coding for a serine protease (NS3) and the first clinical studies on inhibitors of the protease have recently been carried out. Chapter 2 presents a review of the medicinal chemistry approaches to this target. 

The cannabinoid field was reviewed in Progress in Medicinal Chemistry Volume 35. Since that time great advances have been made in our understanding of cannabinoid receptor pharmacology. Many novel ligands have been discovered and several are expected to have exciting clinical utility. Medicinal chemistry approaches to the modulation of cannabinoid receptors are extensively reviewed in Chapter 6. 

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