Sildenafil, discovery

In 1985, the story of sildenafil discovery (159) started when two chemists at Pfizer s site in Kent, U.K. proposed to look for antihypertensive and antianginal compounds that... 

Very often, drugs are discovered through persistent work and continual optimization and many tests and trials. This is exemplified by the history behind the discovery of sildenafil (Viagra, Pfizer), a drug for the treatment of erectile dysfunction, and the AIDS drug zidovidine (Retrovir, GlaxoSmithKline) (Exhibits 3.18 and 3.19). 

The long, tortuous path from drug discovery to commercialization is amply demonstrated by the sildenafil (Viagra) story. 

Discovery and synthesis of sildenafil 13.3 Synthesis of vardenafil 13.4 Synthesis of tadalafil 13.5 References... 

The chemical development of the commercial route to sildenafil also serves as an excellent example of the different issues that need to be considered when moving from drug discovery to commercial quantities. This problem is therefore based on the commercial synthesis of sildenafil as published by the Pfizer research group around P. J. Dunn ... 

Another recent example is provided by the discovery of the use of sildenafil (Viagra Fig. 1.15), a phosphodiesterase type 5 (PDE5) inhibitor, as an efficacious, orally active agent for the treatment of erectile dysfunction [25,26]. Initially, this compound was brought to the clinic as an hypotensive and cardiotonic substance, but its usefulness in erectile dysfunction resulted unexpectedly from clinical observations made during a 10-day toleration study in Wales [27]. 

Campbell, S.F., Science art and drug discovery a personal perspective. Clinical Science, 99,255, 2000. Brock, G., Sildenafil citrate (Viagra ), Drugs of Today, 36, 125, 2000. 

Figure 19.4 Examples of drugs that were derived from translational chemistry, translational research and translational medicine, respectively (1) d-tubocurarine (2) propranolol and (3) esmolol. Also shown is sildenafil, (4), which is probably best considered to have been derived from a composite of all three of these drug discovery starting points. See text for details.

Dr David Brown, Managing Director of Alchemy Biomedical Consulting, Ltd., co-inventor of Viagra (sildenafil), and former Global Head of Discovery Research at Roche, when asked whether the downturn in NDA approvals is a concern for pharmaceutical profitability in the long term replied, Yes, both in numbers and quality. ... 

Since the discovery of sildenafil for the treatment of ED in 1993, two additional products, vardenafil and tadalafil, have been introduced to the market [6, 7]. All these three drugs work by inhibiting type 5 phosphodiesterase (PDE5). This inhibition increases the amount of cyclic guanosine monophosphosphate (cGMP), which... 

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