Introduction

When Evans et al. [44] were looking for new cholecystokinin (CCK) antagonists in 1988, they introduced the concept of ''privileged structures'' for structural motifs which are capable of providing useful ligands for more than one single target. As shown in Fig. 25.5, the benzodiazepine skeleton is a recurring structural motif addressing not only CCK but the structurally similar Trifluadom 2 shows high affinity to the opiate receptor [45] and 3 is an NK-1 antagonist [46].

This finding contradicts the common principles of individuality and selectivity of biological receptors. According to Evans et al., a possible explanation for this phenomenon might be that these G-protein-coupled receptors descend from the same ancestral genes and that they still remain structurally related. Similarly, Wiley and Rich [47] have reasoned that the similar structure of G-protein-coupled receptors which are characterized by seven transmembrane a-helices might favor a recurring binding element. These hydrophobic pockets might be complementary to the different conformations of privileged structures [47]. Therefore, libraries of such privileged structures can give rise to a number of lead compounds in new screening assays [26, 48, 49].

Fig. 25.6. Biphenyltetrazoles as privileged substructures.

Fig. 25.6. Biphenyltetrazoles as privileged substructures.

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Do Not Panic

Do Not Panic

This guide Don't Panic has tips and additional information on what you should do when you are experiencing an anxiety or panic attack. With so much going on in the world today with taking care of your family, working full time, dealing with office politics and other things, you could experience a serious meltdown. All of these things could at one point cause you to stress out and snap.

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