Bioisostere

Bioisosterism is a term used in medicinal chemistry. Two molecules are referred to as bioisoster if they have a similar biological effect in vivo (ie in the living system ) and show are isosteric. An example would be the opiates, in which most are mutually bioisostere, as they have almost the same biological effect. The term is used especially in connection with the so-called rational drug design. The literal translation of bioisosterism means about biologically same effect with the same shape ( isos = equal, steros = Location, shape).

As a bioisosterism a key - lock principle is usually a basis as for mimetics terms bioisosteric agents and mimics overlap.

When considering the bioisosterism the similarity between molecules and their functional groups plays the largest role in terms of their biological effects. A. Burger defined bioisosteric agents as follows:

" Include compounds or groups of molecules with nearly identical shape and volume of the molecule, as well as about the same distribution of electrons, the similar physical properties. "

This definition is broader than about the approach of Langmuir (1919), which requires the same number and the same arrangement of electrons and equally includes the Grimms' hybrid displacement law (1925 ). A similar concept is also the Isolobalkonzept (R. Hoffmann, Nobel Prize in Chemistry in 1981) is based, mainly the shape and energy of the frontier orbitals of the zoom pulls next to the number of electrons to compare molecular fragments.

A distinction that are sterically and electronically very similar ( eg, the halides -F,- Cl, -Br, - I, and the cyano group -CN which each have a binding free show ) and non-classical bioisosters between classical bioisosters. In the latter, the substitutions can be much more complex, such as a cyclic structure ( ring system ) against an acyclic ( open-chain radical).

The importance of bioisosters is particularly evident in the context of metabolic and toxicological considerations. While a benzene ring is easily epoxidized, the bioisosteric Methylthiophengruppe is metabolically stable.

By replacing a carboxylic acid group against a tetrazole ring, the bioavailability is increased significantly with comparable acidity.

In this way, bioisosteric replacements allow the fine tuning of drug properties. A prominent example is the phosphodiesterase -5 inhibitors sildenafil and vardenafil, whereby the patent protection could be circumvented with the latter.