Editorial:Hot Topic: [Exploiting Multivalency in Drug Design(Executive Editor: Diego Munoz-Torrero)]

摘要

Structural manipulation of already marketed drugs, or in general, of known biologically active compounds as a means to get novel drug candidates with improved profiles constitutes a widespread practice in medicinal chemistry. In most cases, from this approach arise novel molecules with a degree of structural complexity similar to that of the parent compound and containing a single pharmacophoric moiety aimed at hitting a single biological target. Another way to get access to novel drug candidates from known drugs that is attracting an ever-expanding interest involves the combination of more than one identical or different pharmacophores rather than the structural modificacion of a single one. This approach results in, obviously more complex, dimeric or hybrid drug candidates with significantly distinct pharmacological profiles relative to the monomeric parent compounds from which they were designed. Thus, combination into a single framework of carefully selected different pharmacophoric moieties can endow the resulting hybrid molecule with the ability to interact with different biological targets, thereby leading to a sequential interference at different levels of a given pathogenic pathway or to a series of complementary pharmacological effects, and, consequently to an enhanced efficiency in the management of that particular disease. Also, hybrid and dimeric drug candidates can be rationally designed to provide multivalent interactions with biological targets having more than one binding site or even with targets which are themselves oligomeric, thus affording a dramatically increased affinity.nnIn this issue, the rationale for the design of representative examples of different classes of multivalent dimeric and hybrid drug candidates is discussed, as well as the advantages they provide over their monomeric counterparts in different therapeutic areas.