Drug designs overview

GR Marshall, CD Barry, HE Bosshard, RA Dammkoehler, DA Dunn. The conformational parameter m drug design The active analog approach. ACS Symp Ser 112 205-226, 1979. YC Martin. Overview of concepts and methods in computer-assisted rational drug design. Methods Enzymol 203 587-613, 1991. 

The previous sections have described methods to obtain 2-pyridone scaffolds. Both in the construction of new materials and especially in drug design and development, there is a desire to be able to derivatize and optimize the lead structures. In the following sections, some recent developments using MAOS to effectively substitute and derivatize 2-pyridone heterocycles are described. The reaction types described range from electrophilic-, and nucleophilic reactions to transition metal-catalyzed transformations (Fig. 7). To get an overview of how these systems behave, their characteristics imder conventional heating is first described in brevity. 

M. R. Reddy and A. Parrill, Overview of rational drug design in Rational Drug Design ... 

Grossman, S.J., Overview drug metabolism in the modem pharmaceutical industry. In Drug Metabolism in Drug Design and Development, Zhang, D., Zhu, M. and Humphreys, W.G. (eds). J. Wiley Sons, Inc., 2008, pp. 3-13. 

It should be pointed out that one is focused on properties of molecules in the absence of the receptor in contrast to the detailed focus on the complex in drug design studies. Many approaches to similarity fail to even consider chirality, a common discriminator of receptors. For a recent overview of the current status of virtual screening in lead discovery, see the review by Oprea and Matter [82]. 

K.L. Kirk, Selective fluorination in drug design and development, an overview of biochemical rationales, Curr. Top. Med. Chem. 6 (2006) 1447-1456. 

These seven groups of compounds, and the diversity of compounds within each group, are the molecular building blocks that enable structure and function. A brief overview of the relevant biochemistry for each class is pertinent to an appreciation of their role in medicinal chemistry and drug design. 

Jain, S. K., Agrawal, A. (2004) De novo drug design an overview. Lndia J Phar Sci 66, 721-728. 

In this overview of fragment-based drug design, we will expand on the application of NMR and X-ray crystallography as the tools for biophysical screening. Common protocols will be presented, as well as the strengths and limitations of each approach. 

Fig. 1. Overview of the role of NMR in drug design and development. NMR methods are indicated in dark boxes. Screening-based approaches are shaded grey.

Figure 1. Overview of structure-based drug design If the three dimensional structure of the target macromolecule is known by X-ray crystallography, NMR, or even homology modeling [7], this can serve as a starting point for what has been termed direct structure-based drug design [8]. This class of problems is usually referred to as receptor-based...

Blood Pressure Lowering Treatment Trialists Collaboration 2000. Effects of ACE inhibitors, calcium antagonists, and other blood-pressurelowering drugs results of prospectively designed overviews of randomised trials. Lancet 355 1955-1964... 

M. R. Reddy and A. Parrill, Overview of rational drug design in Rational Drug Design Novel Methodology and Practical Applications, ACS Symposium Series 719, A. Parrill and M.R. Reddy, eds., Oxford University Press, Washington, DC (1999), pp. 1-11. 

A number of excellent review articles exist, including several that explain MR spectroscopy and detail the impact of MR spectroscopy in drug design and in preclinical studies, and others that provide overviews of human in vivo metabolism and pharmacokinetics measured by 19F MR in fluoropyrimidine compounds as well as in psychotropic compounds [1, 3-5, 7-10, 59, 60-63], In keeping with other facets of drug development, the number of 19F MR clinical investigations is much smaller than the number of animal model, specimen, cell line, or solution experiments. 

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