Isosterism ring equivalents

The substitution of —CH= by — N= in aromatic rings has been one of the most successful applications of classical isosterism (see following paragraph on ring equivalents). Aminopyrine and its isostere are about equally active as antipyretics (Fig. 13.5). 

Finally, ring equivalences are induded to permit isosteric matches between... 

It was with Erlenmeyer that the concept of bioisosterism was introduced to differentiate from classical isosteres, ensuring its relevance to medicinal chemistry. The introduction of ring equivalences is significant. This was the formalization of what we consider to be a bioisosteric comparison and is the first definition of most relevance to medicinal chemistry. 

Another particularly impressive example of ring bio-isosterism is found in the development of the antiulcer H2-receptor histamine antagonists in which the initial imidazole ring was changed to various other equivalents ... 

The imidazole ring or an isosteric equivalent is required to mimic the Hiss side chain of angiotensin II. 

The work of Snyder et al, together with other examples found in the literature, shows that several level of activity can be identified amongst the different isosteres. It has to be kept in mind that the replacement of a ring by its isosteres does not always lead to an iso-active or more active compound (Figure 15.18). But in general, it is possible to obtain at least one or more equivalent systems." ... 

The concept of isosterism was later broadened by Erlenmeyer in 1932 to include elements, ions, or molecules with the same number of electrons at the valence level (Table 2.3) [3]. Erlenmeyer stated that elements in the same column of the periodic table are isosteres among themselves and also introduced the concept of electronically equivalent rings. 

Isosteres are stmctural elements that are deemed to have more or less equivalent chemical or physical properties, and they have been used extensively in modification of lead compounds in order to enhance dmg action. Table 9.1 shows some classical isosteres. The definition of an isostere is an atom or a group in which the peripheral layers of electrons are identical. However, this definition is not adhered to and, for instance, F is often considered as a substitute for H although it has three lone pairs of electrons in its peripheral layer whereas H does not have any. Thus the strict definition of isosteres quite quickly breaks down and, for instance, benzene can be substituted for by a number of ring types and carbonyl and carboxylate substituted by groups which are not that dose to them in stmcture. Thus isosteric substitution is not an exact science. 

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