MIRODENAFIL DIHYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H37N5O5S.2ClH
Molecular Weight	604.589
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of MIRODENAFIL DIHYDROCHLORIDE

Structure Search

SMILES

Cl.Cl.CCCOC1=CC=C(C=C1C2=NC(=O)C3=C(N2)C(CCC)=CN3CC)S(=O)(=O)N4CCN(CCO)CC4

InChI

InChIKey=CKPHITUXXABKDL-UHFFFAOYSA-N

InChI=1S/C26H37N5O5S.2ClH/c1-4-7-19-18-30(6-3)24-23(19)27-25(28-26(24)33)21-17-20(8-9-22(21)36-16-5-2)37(34,35)31-12-10-29(11-13-31)14-15-32;;/h8-9,17-18,32H,4-7,10-16H2,1-3H3,(H,27,28,33);2*1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27034723
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17640490

The inhibition of cyclic nucleotide Phosphodiesterase type 5 (PDE5) has been clinically validated as an effective treatment for erectile dysfunction. One of them is mirodenafil (formerly known as SK-3530) approved only in Korea. This drug was developed by SK Chemicals and marketed under the trade name Mvix.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 5A 31 Target ID: CHEMBL1827 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27034723	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Erectile dysfunction 35 Sources: https://www.skchemicals.com/page/ls/eng/product/info4_01.do	Primary	Approved 8583	Mvix Approved Use Treatment of erectile dysfunction(ED)
Urologic diseases 2 Sources: https://clinicaltrials.gov/ct2/show/NCT01232010	Primary	Phase I 438	Unknown Approved Use Unknown
Kidney disease 6 Sources: https://clinicaltrials.gov/ct2/show/NCT01232010	Primary	Phase I 438	Unknown Approved Use Unknown
Renal insufficiency 40 Sources: https://clinicaltrials.gov/ct2/show/NCT01232010	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
331.1 ng/mL EXPERIMENT https://www.scirp.org/pdf/PP_2014012316183810.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
373.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20110038/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.135 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.079 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	SK-3541 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
122 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	SK-3541 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
404 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
976.5 ng × h/mL EXPERIMENT https://www.scirp.org/pdf/PP_2014012316183810.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
931.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20110038/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.272 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.184 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	SK-3541 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
514 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	SK-3541 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
888 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.81 h EXPERIMENT https://www.scirp.org/pdf/PP_2014012316183810.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.96 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20110038/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.44 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	SK-3541 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.39 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	SK-3541 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.32 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390072/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MIRODENAFIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/	Other AEs: Facial flushing, Headache... Other AEs: Facial flushing (16.22%) Headache (10.81%) Nausea (2.70%) Eye rednes (4.05%) Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/

AEs

AE	Significance	Dose	Population
Headache	10.81%	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/
Facial flushing	16.22%	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/
Nausea	2.70%	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/
Eye rednes	4.05%	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18638004/

PubMed

Title	Date	PubMed
Crystal forms of SK-3530.	2010-12	21191770
The effect of mirodenafil on the penile erection and corpus cavernosum in the rat model of cavernosal nerve injury.	2010-09-24	20861845
Efficacy and Safety of Tadalafil 5 mg Administered Once Daily in Korean Men with Erectile Dysfunction: A Prospective, Multicenter Study.	2010-09	20856651
Efficacy and safety of mirodenafil in men taking antihypertensive medications.	2010-09	20649936
Efficacy and safety of oral mirodenafil in the treatment of erectile dysfunction in diabetic men in Korea: a multicenter, randomized, double-blind, placebo-controlled clinical trial.	2010-08	20626604
Pharmacokinetics of mirodenafil and its two metabolites, SK3541 and SK3544, after intravenous and oral administration of mirodenafil to streptozotocin-induced diabetes mellitus rats.	2010-02	19929308
Pharmacokinetics of mirodenafil, a new erectogenic, and its metabolite, SK3541, in rats: involvement of CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 for the metabolism of both mirodenafil and SK3541.	2010	20456834
The effects of ketoconazole and rifampicin on the pharmacokinetics of mirodenafil in healthy Korean male volunteers: an open-label, one-sequence, three-period, three-treatment crossover study.	2009-12	20110038
Hormonal testing and pharmacologic treatment of erectile dysfunction: a clinical practice guideline from the American College of Physicians.	2009-11-03	19884625
Faster clearance of mirodenafil in rats with acute renal failure induced by uranyl nitrate: contribution of increased protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2.	2009-10	19814864
Dose-dependent pharmacokinetics and first-pass effects of mirodenafil, a new erectogenic, in rats.	2009-09	19639551
Influence of alcohol on the hemodynamic effects and pharmacokinetic properties of mirodenafil: a single-dose, randomized-sequence, open-label, crossover study in healthy male volunteers in Korea.	2009-06	19695390
Determination of mirodenafil and sildenafil in the plasma and corpus cavernous of SD male rats.	2009-02-20	19095395
The penile erection efficacy of a new phosphodiesterase type 5 inhibitor, mirodenafil (SK3530), in rabbits with acute spinal cord injury.	2008-11	19057138
Efficacy and safety of mirodenafil, a new oral phosphodiesterase type 5 inhibitor, for treatment of erectile dysfunction.	2008-11	18638004
Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group clinical trial.	2008-09	18645683
Editorial comment on: chronic treatment with a type 5 phosphodiesterase inhibitor suppresses apoptosis of corporal smooth muscle by potentiating Akt signalling in a rat model of diabetic erectile dysfunction.	2008-06	18243512
Chronic treatment with a type 5 phosphodiesterase inhibitor suppresses apoptosis of corporal smooth muscle by potentiating Akt signalling in a rat model of diabetic erectile dysfunction.	2008-06	18243503
Identification of cytochrome P450 enzymes responsible for N -dealkylation of a new oral erectogenic, mirodenafil.	2008-01	18098061
Development of LC/MS/MS assay for the determination of 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one (SK3530) in human plasma: application to a clinical pharmacokinetic study.	2007-09-21	17689219
Pharmacokinetics and tissue distribution of a novel PDE5 inhibitor, SK-3530, in rats.	2007-08	17640490
Formation of supramolecular hydrogels with controlled microstructures and stability via molecular assembling in a two-component system.	2007-03-01	17141263
Validation of a HPLC method for the quantification and purity determination of SK3530 in drug substance and tablet.	2007-02-19	17134866
Metabolism and excretion of 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydropyrrolo[3,2-d]-pyrimidin-4-one (SK3530) in rats.	2007	17318927

Sample Use Guides

In Vivo Use Guide

One tablet (Mirodenafil 50mg or 100mg) recommended dosing frequency is once per day. Taken orally approximately 60 minutes before sexual activity. Sexual stimulation is required for a response to treatment.

Route of Administration: Oral

In Vitro Use Guide

The in vitro incubation of [14C]SK-3530 (MIRODENAFIL )with rat and human plasma samples resulted in high protein binding rates of more than 97%; binding was concentration-independent over the range tested (1–100 µmol/L), with no difference between the species show.

Name

Type

Language

MIRODENAFIL DIHYDROCHLORIDE

Systematic Name

English

SK-3530

Preferred Name

English

1-PIPERAZINEETHANOL, 4-((3-(5-ETHYL-4,5-DIHYDRO-4-OXO-7-PROPYL-1H-PYRROLO(3,2-D)PYRIMIDIN-2-YL)-4-PROPOXYPHENYL)SULFONYL)-, DIHYDROCHLORIDE

Systematic Name

English

5-ETHYL-3,5-DIHYDRO-2-(5-((4-(2-HYDROXYETHYL)-1-PIPERAZINYL)SULFONYL)-2-PROPOXYPHENYL)-7-PROPYL-4H-PYRROLO(3,2-D)PYRIMIDIN-4-ONE HYDROCHLORIDE (1:2)

Systematic Name

English

4H-PYRROLO(3,2-D)PYRIMIDIN-4-ONE, 5-ETHYL-3,5-DIHYDRO-2-(5-((4-(2-HYDROXYETHYL)-1-PIPERAZINYL)SULFONYL)-2-PROPOXYPHENYL)-7-PROPYL-, HYDROCHLORIDE (1:2)

Systematic Name

English

Mirodenafil hydrochloride [WHO-DD]

Common Name

English

MIRODENAFIL HYDROCHLORIDE

Systematic Name

English

Code System Code Type Description

PUBCHEM

135564928