224785-90-4 Usage
Description
Vardenafil is a new PDE5 inhibitor launched for oral treatment of male erectile
dysfunction and it has significant structural similarity with sildenafil (Viagra?), which
was the first PDE5 inhibitor introduced in 1998 for this indication. Vardenafil 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
vardenafil (IC50=0.7 nM) is ～10 times greater than that of sildenafil (IC50=6.6 nM).
Vardenafil 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 sildenafil
(tmax=1.16 h) and tadalafil (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. Vardenafil is
metabolized in the liver primarily by CYP3A4 and is eliminated mainly in feces. In
clinical studies, 10–20 mg doses of vardenafil 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 vardenafil
is similar to that of sildenafil, with headache, flushing, dyspepsia and nasal congestion
being the most common adverse events. Vardenafil 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 vardenafil were 6.9 and 4.3 mmHg, respectively, when compared to placebo. However, single and multiple oral doses of vardenafil up to 40 mg
produced no clinically relevant changes in the ECGs of normal male volunteers.
Originator
Bayer AG (Germany)
Uses
Different sources of media describe the Uses of 224785-90-4 differently. You can refer to the following data:
1. erectil dysfunction;PDE5 inhibitor
2. Vardenafil Hydrochloride Trihydrate (cas# 330808-88-3) has therapeutic applications and used in cosmetics and personal care products.
Definition
ChEBI: The sulfonamide resulting from formal condensation of the sulfo group of 4-ethoxy-3-(5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(1H)-one-2-yl)benzenesulfonic acid and the secondary amino group of 4-ethylpiperazine.
Brand name
Levitra
Flammability and Explosibility
Nonflammable
Clinical Use
Treatment of erectile dysfunction
Drug interactions
Potentially hazardous interactions with other drugs
Alpha-blockers: enhanced hypotensive effect - avoid
for 6 hours after alpha-blockers (max dose 5 mg).
Antifungals: concentration increased by
ketoconazole, and itraconazole - avoid concomitant
use.
Antivirals: concentration increased by fosamprenavir,
indinavir and ritonavir- avoid with indinavir and
ritonavir; increased risk of ventricular arrhythmias
with saquinavir - avoid; avoid with telaprevir, use
tipranavir with caution.
Cobicistat: concentration of vardenafil possibly
increased - reduce dose of vardenafil.
Grapefruit juice: concentration possibly increased -
avoid concomitant use.
Nicorandil: possibly enhanced hypotensive effect -
avoid concomitant use.
Nitrates: possibly enhanced hypotensive effect -
avoid concomitant use.
Riociguat: enhanced hypotensive effect - avoid
concomitant use.
Metabolism
Vardenafil is metabolised in the liver primarily by
cytochrome P450 isoenzymes CYP3A4 (the major route)
as well as CYP3A5 and CYP2C isoforms. The major
metabolite produced by desethylation of vardenafil also
has some activity.
Vardenafil is excreted as metabolites mainly in the faeces
(91 to 95%), and to a lesser extent in the urine.
Check Digit Verification of cas no
The CAS Registry Mumber 224785-90-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,2,4,7,8 and 5 respectively; the second part has 2 digits, 9 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 224785-90:
(8*2)+(7*2)+(6*4)+(5*7)+(4*8)+(3*5)+(2*9)+(1*0)=154
154 % 10 = 4
So 224785-90-4 is a valid CAS Registry Number.
InChI:InChI=1/C23H32N6O4S.ClH.3H2O/c1-5-8-20-24-16(4)21-23(30)25-22(26-29(20)21)18-15-17(9-10-19(18)33-7-3)34(31,32)28-13-11-27(6-2)12-14-28;;;;/h9-10,15H,5-8,11-14H2,1-4H3,(H,25,26,30);1H;3*1H2
224785-90-4Relevant articles and documents
A METHOD FOR THE PREPARATION AND ISOLATION OF SALTS OF VARDENAFIL WITH ACIDS
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Page/Page column 17, (2013/06/06)
The subject of this invention provides a method of preparation and isolation of water-insoluble or partially soluble salts of vardenafil of formula 1, in particular its salts with acids in the ratio of components 1 : 1 (of formula 2a, HA stands for any acid), and of crystalline hydrates of said salts. These solid forms, in particular crystalline vardenafil hydrochloride trihydrate of formula 4, can be directly, without additional purification, used in preparation of a medicine for the therapy of erectile dysfunction. The present solution is based on using water as a suitable medium both for obtaining of extracts of the water-soluble forms of vardenafil, and for isolation and subsequent crystallization of solid water-insoluble or partially soluble salts of vardenafil with acids (1 : 1). Crystallization of the isolated salts takes place after adjustment of pH of the aqueous solutions by means of aqueous solutions of bases or acids, wherein no organic solvent or a mixture thereof with water is needed for the crystallization. The method according to this invention reduces costs for organic solvents, increases efficiency of isolation of the vardenafil salts with acids, and facilitates preparation of poorly stable hydrates of these salts.
PROCESSES FOR THE PREPARATION OF VARDENAFIL
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, (2011/02/24)
The present invention provides processes for the preparation of vardenafil, its pharmaceutically acceptable salts, hydrates and intermediates.
A PROCESS FOR THE PREPARATION AND ISOLATION OF VARDENAFIL AND SALTS THEREOF
-
, (2011/07/30)
A new process for the preparation of vardenafil and isolation of its salts, in particular a citric acid salt and a crystalline form of the salt is disclosed.
