Udenafil

Description

Udenafil is the fourth in a class of drugs targeting the inhibition of the enzyme phosphodiesterase 5 (PDE5) for the treatment of erectile dysfunction. Inhibition of PDE5 results in the increase in endogenous cyclic guanosine monophosphate (cGMP) concentrations in the penile corpus cavernosum. cGMP induces smooth muscle cell relaxation and subsequent increased blood flow leading to a sustainable erection. Udenafil is a potent antagonist of human PDE5 with an IC₅₀ of 8.25nM and a comparable selectivity profile as sildenafil for the other PDEs. Unlike tadalafil, it does not inhibit PDE11, which has been implicated in myalgia and testicular toxicity. Furthermore, udenafil produced up to a 91% vaginal penetration success rate and up to a 67% intercourse completion rate compared to a 29% completion rate by placebo. Overall patient satisfaction, measured by a standard global assessment question, was 86% compared to only 26% in the placebo group. The most frequently recorded adverse events were mild-to-moderate facial flushing and headache.

Description

Udenafil is an inhibitor of phosphodiesterase 5 (PDE5). In vivo, udenafil (1 and 5 mg/kg) increases lung cGMP levels, attenuates the development of compensatory right ventricular hypertrophy, and reduces pulmonary arterial wall thickening in a rat model of monocrotaline-induced pulmonary hypertension. It increases creatine clearance and decreases blood urea nitrogen (BUN) and serum malondialdehyde (MDA) levels in a rat model of renal ischemia-reperfusion injury. Udenafil (0.3 and 10 mg/kg) induces penile erections in conscious rabbits and in rabbits with acute spinal cord injury.

Chemical properties

Off-White Solid

Originator

Dong-A (South Korea)

The Uses of Udenafil

Udenafil is an oral phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction.

What are the applications of Application

Udenafil is an oral PDE5A (phosphodiesterase 5) inhibitor.

Background

Udenafil is a new phosphodiesterase type 5 (PDE5) inhibitor used to treat erectile dysfunction (ED). It has been approved in South Korea and will be marketed under the brand name Zydena. It is not yet approved for use in the U.S., E.U., or Canada.

Indications

Investigated for use/treatment in erectile dysfunction and hypertension.

Definition

ChEBI: Udenafil is a sulfonamide.

brand name

Zydena

Pharmacokinetics

Udenafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor.

Synthesis

Udenafil has a unique pharmacokinetic profile with a relatively rapid onset and sufficiently long duration (Tmax 1-1.5 hr, t1/2 11-13 hr) to make it effective for up to 24 hours. Synthesis of this racemic compound started with commercially available 2-propoxybenzoic acid (160). The free acid 160 was converted to it acyl chloride with thinoy chloride in refluxing dichloromethane, which was condensed with 4-amino-1-methyl-3- propyl-1H-pyrazole-5-carboxamide (161) with TEA and DMAP in dichloromethane to yield carboxamide 162 in 85% yield from 160. Compound 162 was sulfonated with chlorosulfonic acid to yield benzenesulfonyl chloride 163 in 67% yield, which was treated with racemic 2-(1-methylpyrrolidin- 2-yl)ethylamine (164) in dichloromethane to afford sulfonamide 165 in 80% yield. Finally, compound 165 was cyclized with tBuOK in refluxing tBuOH to give udenafil (XXII) in 81% yield.

Metabolism

Hepatic. Metabolized by CYP3A4 and CYP3A5.