Rational drug discovery

FIGURE 28.4 The rational drug discovery paradigm directed at a molecular target. 

HIV protease inhibitors/ of metoprolol as an antihypertensive/ and of methotrexate as an antifolate antitumor therapy. 

In addition to biological and retroactive approaches to molecular target definition, one can also return to classical approaches of cell metabolism and biochemistry. Since these suggest single targets, they can be inefficient. Chemical genetics approaches have recently been explored with libraries of molecules and precisely defined organisms. 

FIGURE 28.6 Stmcture of tw O compounds in the geldanamycin class. Cancer Chemotherapy National Service Center (NSC) numbers are showni wdth structural details. 

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Rating programs Rational design Rational drug discovery Rauwolfia serpentina Rauwolscine [131-03-3]... 

Theil FP, Guentert TW, Haddad S, Poulin P. Utility of physiologically based pharmacokinetic models to drug development and rational drug discovery candidate selection. Toxicol Lett 2003 Feb 18 138(l-2) 29-49. Review. 

Bajorath, J. (2001) Rational drug discovery revisited Interfacing experimental programs with bio- and chemo-informatics. Drug Discov. Today 6, 989-995. 

Saragovi, H. et al. (1992). Loops and secondary structure mimetics development and applications in basic science and rational drug discovery. Bio j Technology 10, 1131-111. 

This expense is a strong motivation for medical researchers to develop a more efficient means of drug discovery than the old trial-and-error method. Rational drug discovery is the name given to techniques that employ the principles of chemistry and physics, or are guided by experimental data, to aid in the search for new drugs. 

In Table 3 the different models are listed with regard to their potential contribution to a rational drug discovery and development process. 

Noble, D. and Colatsky, T. J. A return to rational drug discovery computer-based models of cells, organs and systems in drug target identification. Emerging Therapeutic Targets 2000, 4 39 49. 

Even in today s more rational drug discovery environment, it may be said that serendipity is one of the medicinal chemist s best friends. Of course, serendipity alone cannot provide a drug it requires someone to recognize the opportunity and capitalize on it. As demonstrated by Sternbach and his colleagues, when chance discoveries fall into the hands of open-minded and persistent scientists, the results can be remarkable. 

Kalvass JC, Maurer TS (2002) Influence of nonspecific brain and plasma binding on CNS exposure implications for rational drug discovery. Biopharm Drug Dispos 23(8) 327-338... 

The core of any rational drug discovery program is medicinal chemistry. Although the synthesis of modified nucleic acids has been a subject of interest for some time, the intense focus on the medicinal chemistry of oligonucleotides dates perhaps to no more than 5 years before the preparation of this chapter. 

Figure 3.2 The basic steps of the rational drug discovery process...

NMR spectroscopy is a powerful tool for chemistry and structural biology, especially when NMR is applied to study protein-ligand interactions. In the drug discovery process, NMR is used to study whether a compound binds to a protein up to the determination of the full three-dimensional structure of the complex.Rational drug discovery requires an early appraisal of all factors impacting on the likely success of a drug candidate in the subsequent preclinical, clinical and commercial phases of dug development. Tlie study of absorption, distribution, metabohsm and excretion/pharmacokinetics (ADME/PK) has de-... 

K. Kuwata, Rational Drug Discovery for Prion Disease , Tanpakushitsu Kakusan Koso, 2008, 53, 727. 

The following conclusions can be offered when comparing reverse pharmacology with rational drug discovery and manufacturing ... 

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