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Identification
NameUdenafil
Accession NumberDB06267
TypeSmall Molecule
GroupsApproved, Investigational
Description

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.

Structure
Thumb
Synonyms
SynonymLanguageCode
DA-8159Not AvailableNot Available
UdenafilNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ZydenaNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number268203-93-6
WeightAverage: 516.656
Monoisotopic: 516.25187436
Chemical FormulaC25H36N6O4S
InChI KeyIYFNEFQTYQPVOC-UHFFFAOYSA-N
InChI
InChI=1S/C25H36N6O4S/c1-5-8-20-22-23(31(4)29-20)25(32)28-24(27-22)19-16-18(10-11-21(19)35-15-6-2)36(33,34)26-13-12-17-9-7-14-30(17)3/h10-11,16-17,26H,5-9,12-15H2,1-4H3,(H,27,28,32)
IUPAC Name
3-{1-methyl-7-oxo-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-5-yl}-N-[2-(1-methylpyrrolidin-2-yl)ethyl]-4-propoxybenzene-1-sulfonamide
SMILES
CCCOC1=C(C=C(C=C1)S(=O)(=O)NCCC1CCCN1C)C1=NC(=O)C2=C(N1)C(CCC)=NN2C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsPyrazolopyrimidines; Phenol Ethers; Alkyl Aryl Ethers; Pyrimidones; Pyrrolidines; Sulfonamides; Sulfonyls; Pyrazoles; Tertiary Amines; Polyamines
Substituentsphenol ether; alkyl aryl ether; pyrimidone; pyrimidine; sulfonamide; sulfonyl; sulfonic acid derivative; azole; pyrazole; pyrrolidine; tertiary amine; ether; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Pharmacology
IndicationInvestigated for use/treatment in erectile dysfunction and hypertension.
PharmacodynamicsUdenafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor.
Mechanism of actionUdenafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by udenafil enhances erectile function by increasing the amount of cGMP.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. Metabolized by CYP3A4 and CYP3A5.

SubstrateEnzymesProduct
Udenafil
N-desalkyludenafilDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.5
Caco-2 permeable - 0.8957
P-glycoprotein substrate Substrate 0.8093
P-glycoprotein inhibitor I Inhibitor 0.6138
P-glycoprotein inhibitor II Inhibitor 0.658
Renal organic cation transporter Non-inhibitor 0.784
CYP450 2C9 substrate Non-substrate 0.6694
CYP450 2D6 substrate Substrate 0.6391
CYP450 3A4 substrate Substrate 0.721
CYP450 1A2 substrate Non-inhibitor 0.8355
CYP450 2C9 substrate Inhibitor 0.5391
CYP450 2D6 substrate Non-inhibitor 0.8885
CYP450 2C19 substrate Non-inhibitor 0.8588
CYP450 3A4 substrate Inhibitor 0.8863
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5793
Ames test Non AMES toxic 0.5747
Carcinogenicity Non-carcinogens 0.5502
Biodegradation Not ready biodegradable 0.8961
Rat acute toxicity 2.6102 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8455
hERG inhibition (predictor II) Inhibitor 0.805
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0798ALOGPS
logP3.2ALOGPS
logP1.66ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)7.21ChemAxon
pKa (Strongest Basic)8.48ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area117.92 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity153.11 m3·mol-1ChemAxon
Polarizability56.34 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Chan-Ho Lee, Chang-Yong Shin, Seul-Min Choi, Kyung-Koo Kang, Dong-Seong Kim, Byoung-Ok Ahn, Moo-Hi Yoo, “ACID ADDITION SALT OF UDENAFIL, PREPARATION METHOD THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME.” U.S. Patent US20110306762, issued December 15, 2011.

US20110306762
General Reference
  1. Ji HY, Shim HJ, Yoo M, Park ES, Lee HS: Transport of a new erectogenic udenafil in Caco-2 cells. Arch Pharm Res. 2007 Sep;30(9):1168-73. Pubmed
  2. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. Epub 2008 Feb 28. Pubmed
External Links
ResourceLink
KEGG DrugD10027
PubChem Compound6918523
PubChem Substance99443240
ChemSpider5293720
Therapeutic Targets DatabaseDAP000960
PharmGKBPA164776753
WikipediaUdenafil
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Isosorbide DinitrateThe vasodilatory effects of Isosobide dinitrate may be increased by Udenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Isosorbide MononitrateThe vasodilatory effects of Isosobide mononitrate may be increased by Udenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
NitroglycerinThe vasodilatory effects of Nitroglycerin may be increased by Udenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Food InteractionsNot Available

Targets

1. cGMP-specific 3',5'-cyclic phosphodiesterase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cGMP-specific 3',5'-cyclic phosphodiesterase O76074 Details

References:

  1. Gur S, Sikka SC, Hellstrom WJ: Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress. Expert Opin Investig Drugs. 2008 Jun;17(6):855-64. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Ahn GJ, Chung HK, Lee CH, Kang KK, Ahn BO: Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis. Asian J Androl. 2009 Jul;11(4):435-42. Epub 2009 May 25. Pubmed
  4. Zhao C, Kim SH, Lee SW, Jeon JH, Kang KK, Choi SB, Park JK: Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. BJU Int. 2010 Nov 5. Pubmed
  5. Kouvelas D, Goulas A, Papazisis G, Sardeli C, Pourzitaki C: PDE5 inhibitors: in vitro and in vivo pharmacological profile. Curr Pharm Des. 2009;15(30):3464-75. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Ji HY, Lee HW, Kim HH, Kim DS, Yoo M, Kim WB, Lee HS: Role of human cytochrome P450 3A4 in the metabolism of DA-8159, a new erectogenic. Xenobiotica. 2004 Nov-Dec;34(11-12):973-82. Pubmed
  2. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. Epub 2008 Feb 28. Pubmed

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. Epub 2008 Feb 28. Pubmed

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Drug created on March 19, 2008 10:20 / Updated on September 16, 2013 18:03