Indole-type PDE5 Inhibitors

Since most standard medicinal chemistry issues (potency, selectivity, pK, etc.) have been addressed with various inhibitor classes and since three compounds are already on the market, new PDE5 inhibitors in the future may be especially relevant in indications distinct from male erectile dysfunction, as dual (or multiple)-specificity PDE inhibitors, or as templates for the synthesis of other PDE or kinase inhibitors. 

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Figure 9.11 Indole-type PDE5 inhibitors. In contrast to the substrate-analogous inhibitors, the key glutamine residue is engaged in only a single - not a bidentate - H bond to the indole NH of tadalafil (see inset).

Figure 9.12 Indole type PDE5 inhibitors lacking the diketopiperazine ring.

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