Active analogue approach

Marshall GR, Barry CD, Bosshard HE, Dammkoehler RA, Dunn DA. The conformational parameter in drug design the active analogue approach. In Olson EC, Christoffersen RE, editors, Computer-assisted drug design. Washington, DC American Chemical Society, 1979. p.205-26. 

Active analogue approach In the absence of information regarding the receptor a medicinal chemist may modify known active structures from which one or several pharmacophoric patterns can be deduced. Then a set of possible (low energy) conformations for each compound known to activate the receptor is calculated. For each allowed conformation, the pharmacophoric pattern is determined. The intersection of all generated pharmacophoric patterns may then yield the pharmacophore embedded in all compounds of the set of active analogues. 

The preparation of optically active analogues of the natural amino acids has proven reasonable using the reaction of tris(trimethylsilyl) phosphite with chiral aldimines prepared from optically active amines.225 The asymmetric induction has been observed to be as high as 80%, a significant competitive process compared to the multistep approaches available.226227 An alternative one-step approach involving asymmetric induction upon addition to an aldimine derived from a chiral N-substituted urea provided a product with less desirable optical purity.228... 

Three-Dimensional Quantitative Structure-Activity Relationship Approaches An early study by Seidel et al. showed that a certain 3D feature, such as a torsion angle, can be used to help explain calcium channel activity of a series of DHPs [123], For a set of rigid analogues of nifedipine, their calcium channel affinities (log A)) were correlated with the deviation from 90° of the torsion angle between the two rings (Aa) ... 

In qualitative read-across the potential of a chemical to exhibit a property is inferred from the established potential of one or more analogues. The analogue approach could simply be regarded as the use of SAR. The process involves (1) the identification of a chemical substructure that is common to two substances (which are considered to be analogues) and (2) the assumption that the presence (or absence) of a property/activity for a substance can be inferred from the presence (or absence) of the same property/activity for the analogous substance. 

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