Va-rdenafil is a new PDE5 inhibitor launched for oral treatment of male erectile dysfunction and it has significant structural similarity with sildena-fil (Via-gra?), which was the first PDE5 inhibitor introduced in 1998 for this indication. Var-denafil is synthesized in three steps starting with a cyclization reaction of 2-ethyoxybenzamidine with 2-butyramidopropionic acid and ethoxyallyl chloride to construct the imidazotriazine ring system, followed by sulfonation to the corresponding sulfonyl chloride and subsequent condensation with 1-ethylpiperazine. The potency of PDE5 inhibition by vardena-fil (IC50=0.7 nM) is ～10 times greater than that of sildena-fil (IC50=6.6 nM). Var-denafil is typically administered in single doses of 10 and 20 mg. The time to reach maximum plasma concentration is 0.75 h, which is slightly shorter than those of silde-nafil (tmax=1.16 h) and ta-dalafil (tmax=2h), and the half-life is 4–5 h. Although it is almost completely absorbed following oral administration, the mean absolute bioavailability of a 10 mg dose is ～15%, resulting from extensive first pass metabolism. Va-rdenafil is metabolized in the liver primarily by CYP3A4 and is eliminated mainly in feces. In clinical studies, 10–20 mg doses of var-denafil was well tolerated and efficacious in patients with ED of various severities, including subjects with comorbidities such as diabetes mellitus or hypertension or hyperlipidemia. The side-effect profile of vardena-fil is similar to that of sildena-fil, with headache, flushing, dyspepsia and nasal congestion being the most common adverse events. Vardena-fil has systemic vasodilatory properties, which can cause transient decrease in supine blood pressure; however, it does not appear to translate into clinical effects. The mean maximum decreases in supine systolic blood pressure following 20 and 40 mg vardena-fil were 6.9 and 4.3 mmHg, respectively, when compared to placebo. However, single and multiple oral doses of var-denafil up to 40 mg produced no clinically relevant changes in the ECGs of normal male volunteers.

CAS:	224785-90-4
MF:	C23H32N6O4S
MW:	488.6
EINECS:	607-088-5
Product Categories:	API;Levitra;Erectile Dysfunction;Inhibitor
Mol File:	224785-90-4.mol

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