16 – IDENTICAL AND NON-IDENTICAL TWIN DRUGS

Drugs containing two pharmacophoric groups covalently bounded in a single molecule are called twin drugs. The combination of two identical pharmacophoric entities will lead to an identical twin drug, whereas the association of two different drug entities will generate a nonidentical twin drug. The first strategy consists of molecular variations based on duplication, while the second one results from associative synthesis. Identical and nonidentical twin drugs may be combined by a linker, a no linker, or in overlap mode. The spacer group can be a single bond, a polymeric chain, or in somes cases, an aromatic or nonaromatic cycle. Identical twin drugs may have different modes of connection of the two drug entities. Referring to polymer chemistry nomenclature, each molecule can be formally represented with a head and a tail. Thus, a head-to-head, a tail-to-tail or a head-to-tail connection is possible. The first and the second modes generate symmetrical compounds, which represent the major part of the identical twin drugs described in the literature. However, nonsymmetrical drugs, such as amentoflavone, are not uncommon. Nonidentical twin drugs are also named dual acting drugs or hybrids because of the different pharmacological responses targeted by the two pharmacophoric moities. The design of dual acting drugs, called the symbiotic approach, can be accomplished according to two strategies.