Tadalafil analogs

Figure 9.13 Tadalafil analogs without an indole ring, and related compounds.

Figure 9.17 Tadalafil analogs leading to novel antiplasmodial compounds.

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).

Other compounds, such as 51 and 52, seem to also bear some resemblance to the structural topology found in tadalafil, although the analogy is much less clear... 

Although the trimethoxyphenyl part shows some similarity to the methylene-dioxyphenyl group in tadalafil and both are connected to a hydrophobic aromatic core residue, the H-bond donor function is lacking. On the other hand, for the analogs of 51, the presence of the carbonyl groups was also found to be important, another parallel to the SAR in the tadalafil series. 

Gratz SR, Gamble BM, Flurer RA. Accurate mass measurement using Fourier transform ion cyclotron resonance mass spectrometry for structure elucidation of designer drug analogs of tadalafil, vardenafil and sildenafil in herbal and pharmaceutical matrices. Rapid Commun Mass Spectrom 2006 20 2317-2327. 

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