Conjunctive approaches

Cyclizing open structures or creating an additional ring system in a given structure represents one of the useful methods in the search for biologically active conformations. The end result is a more constraint molecule, with an imposed conformation. This strategy is related to the conjunctive approach developed further on in this chapter. 

The well-known angiotensin converting enzyme (ACE) inhibitor captopril has a relatively simple structure and therefore represents an excellent starting material for the conjunctive approaches (Figure 16.42). 

Finally, when additional moieties are grafted to the molecule, one speaks of conjunctive approaches. They can also consist in the attachment of additional structural elements as in the association of two separate drugs (associative synthesis, non-symmetrical twin drugs, the symbiotic approach or in the duplication of the parent drug (symmetrical twin drugs). 

Fig. 18.2 Conjunctive approach in drug design. The attachment of two benzylic groups and a hydroxyi in S-configuration changes a GABAb receptor agonist into a GABAb antagonist, similarly the H2-histaminergic agonist impromidine is the result of a conjunctive approach applied to histamine. ...

Trahelsi, S, Elouedi, Z, Mellouli, K, (2007) Pruning hehef decision tree methods in averaging and conjunctive approaches, hrtemational Journal of Approximate Reasoning, 46, pp. 568-595. 

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