Chemistry Reference
In-Depth Information
acid sensibility, the phenoxymetyl group, a more electron-withdrawing isoster
than the benzyl group, is used in Penicillin V (Fig.
16
), reducing the
nucleophilicity of the carbonyl and, consequently, its susceptibility to the acid
attack, allowing the Penicillin V to be taken orally [40].
Another approach already used in penicillins is the change or modification of the
benzilic system by a bulkier group to avoid the enzimatic beta lactamase
degradation induced for some bacteria as an antibiotic resistance mechanism.
Nafcillin and oxacillin (Fig.
17
) are interesting examples of beta-lactamic drugs
with bulkier groups acting as steric shields, making them resistant to bacterial
beta-lactamases [40].
Figure 17:
Structures of beta-lactamic antibiotics Nafcillin and Oxacillin.
Burimamide (Fig.
18
) is a compound developed as a histamine H2-receptor
antagonist to the treatment of gastric ulcer. Despite the good inhibitory activity,
it's not absorbed by the gut wall and lacks oral bioavailability. This stimulated the
development of methiamide (Fig.
18
) by adding a methyl group in the position 4
of the imidazolic ring and the change of a carbon atom by a sulfur atom in the side
chain, reducing the ionization of the imidazol ring and giving methiamide a good
oral bioavailability and 10 times more potency. Unfortunately, the metabolism of
the thiourea group causes toxicity and methiamide wasn't approved in phase I
