Active-analog approach

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. 

Marshall GR, Barry CD, Bosshard HE, Dammkoehler RA, Dunn DA. The conformational parameter in drug design The active analog approach. Computer-assisted drug design. ACS Symposium Series 112. Washington DC American Chemical Society, 1979. p. 205-26. 

Fig. 1.3 Analysis of TRH (a) analogs by the active-analog approach by Font and Marshall led to a proposal for the receptor-bound conformation compatible with internal cyclization to generate polycyclic analogs (b).

Validation of the Active-Analog Approach and Active-Site Modeling... 

Inhibitors of the angiotensin-converting enzyme (ACE) served as a test bed for the active-analog approach in which one tries to deduce the receptor-bound conformation... 

Marshall, G.R., Barry, C.D., Bosshard, H.E., Dammkoehler, R.A., Dunn, D.A. The conformational parameter in drug design the active analog approach. In Computer-Assisted Drug Design, Olson, E.C. Christoffersen, R.E. (eds). American Chemical Society, Washington, DC, 1979, 205-226. 

Selecting chemical feature types for the construction of pharmacophores is the most important step towards pharmacophore creation. In early pharmacophore modeling techniques such as the active analog approach described by Marshall et al. [34], pharmacophore features could contain any fragment or atom type. Later techniques such as the software package Catalyst [35], however, use a... 

The active analog approach in general, whereby a set of compounds is synthesized so as to mimic features of a chosen natural compound, has been successful [1]. The active analog approach includes the pharmacophore. The concept of the pharmacophore is to look at features common to a set of drugs or compounds binding to and acting on the same receptors. 

F ure 3.29. The use of active-site models in the Active Analog Approach. The structure shown is one of a series of ACE inhibitors analyzed. The thick gray lines are noncovalent interactions between the inhibitor and active-site points in the enzyme. The dashed lines correspond to the six interatomic distances monitored for each of the inhibitors analyzed... 

Figure 3.46. The flow of information in the Active Analog Approach (111, 399).Sterically allowed conformations (represented by filled circles on the o, torsional grid) of a molecule are determined...

Flexible peptides can be conformationally restricted by a variety of methods other than macrocyclization of the peptide. For example, Marshall et al. introduced a-methyl amino acid substituents into peptides as a way to decrease the conformational space available to the resulting peptide (42) these types of approaches led to his "Active Analog" approach for determining bioactive conformations of flexible molecules (43). Some other traditional... 

D. A. The conformational parameter in drug design the active analog approach. In Computer-assisted Drug Design. (Eds., Olson, E, C., and Christofferson, R. 

The Conformational Parameter in Drug Design The Active Analog Approach... 

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