A Sildenafil

FIGURE 8.16 Left panel showed the chromatogram of mixed standards. Peak identification sildenafil (tR = 7.9), vardenafil (tR = 8.8) and tadalafil (tR = 14.8). The concentration of the three compounds in the mixture was 16, 45, and 22 g/mL, respectively. Right panel showed the mass spectrum of examined analytes. (A) Sildenafil, (B) vardenafil, and (C) tadalafil. 

Fig. 7.16 Hydrophilicity index (a) and cumulative imprinting factors (b) measured for a Sildenafil imprinted poly(MAA-co-HEMA-co-EDMA) library produced using toluene as poro-gen. The arrows indicate a composition leading simultaneously to a high HI and IF...

Langtry HD, Markham A. Sildenafil A review of its use in erectile dysfunction. Drugs 1999 57 967-989. 

Fig. 7. Comparison of the chemical structures of (a) sildenafil (5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonyl-phenyl]-1-methyl-3-propyl-4H-pyrazolo[5,4-e]pyrimidin-7-one) and (b) vardenafil (2-[2-ethoxy-5-(4-ethylpiperazin-1-yl) sulfonylphenyl]-5-methyl-7-propyl-1 H-imidazo[5,1 -f][1,2,4]triazin-4-one) illustrates that these retain the bicyclic guanine core, but differ in the arrangement of nitrogen atoms. Comparison of the cocrystal structures of PDE5 in complex with sildenafil (PDB ID 2H42) and vardenafil (PDB ID 1UHO) shows that the binding mode of both sildenafil and vardenafil is similar to the binding mode of the guanine ring in the 5 -GMP complex. The interaction with the conserved Gln817 is shown.

On December 3, 2004, Pfizer filed for approval to market a sildenafil citrate formulation under the trade name Revatio for the treatment of pulmonary hypertension. The FDA granted priority review and again the drug was approved within 6 months on June 3, 2005, adding yet another twist to the sildenafil citrate story. 

A heterocycle is a cyclic compound that contains atoms of two or more elements in its ring, usually carbon along with nitrogen, oxygen, or sulfur. Heterocyclic amines are particularly common, and many have important biological properties. Pyridoxal phosphate, a coenzyme sildenafil (Viagra),... 

Erectile dysfunction is treated by local or systemic application of vasodilator drugs. The most effective is sildenafil, a phosphodiesterase-type 5 inhibitor. 

Inhaled NO has been used for treatment of persistent pulmonary hypertension of newborn infants, critical respiratory failure of preterm infants, and acute hypertension of adult cardiac surgery patients. PDE-5 inhibitors such as sildenafil are also effective for treatment of pulmonary hypertension. The combination of PDE-5 and NO inhalation yields additive beneficial effects on pulmonary hemodynamics. On the other hand, measurement of exhaled NO is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with bronchial asthma. 

Gibson A (2001) Phosphodiesterase 5 inhibitors and nitrergic transmission—from zaprinast to sildenafil. Eur J Pharmacol 411 1-10... 

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

Even on a relatively small subset of reused data, it is possible to license old medicines for new therapeutic applications and greatly reduce the costs of clinical development—many of these reused medicines have already passed muster for pharmacokinetic safety, so smaller-scale clinical trials are possible, saving considerable money (e.g., Arakis—soon to become Sosei). Even Sildenafil may have new indications [39]. There are huge potential reserves of information to mine in each and every large pharmaceutical company ... 

Involved in penile erection sildenafil citrate (Viagra) affects this process by inhibiting a cGMP phosphodiesterase... 

In Malaysia, interference from the outside, political or otherwise, regarding decisions of the regulatory authority is rare. A recent exception was the debate over the registration of sildenafil (Viagra ), for the treatment of erectile dysfianction. 

Khan KM et al. (2005) A facile and improved synthesis of sildenafil (Viagra) analogs through solid support microwave irradiation possessing tyrosinase inhibitory potential, their conformational analysis and molecular dynamics simulation studies. Mol Divers 9(l-3) 15-26... 

Recent use (within 24 h of sildenafil or vardenafil or within 48 h of tadalafil) of a phosphodiesterase-5 inhibitor for erectile dysfunction (or pulmonary hypertension)... 

The most dramatic difference between the three agents is tadalahl s extended duration of action, earning it the nickname the weekender drug. While sildenafil and vardenafil have average half-lives of 3 to 4 hours, tadalafil s half life is approximately 18 hours.18 The extended half-life allows for more spontaneous sexual activity over a couple of days, but may increase the duration of adverse effects and liklihood of drug interactions or sildenafil. 

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