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139755-83-2 molecular structure
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5-{2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-7-one

ChemBase ID: 88
Molecular Formular: C22H30N6O4S
Molecular Mass: 474.5764
Monoisotopic Mass: 474.20492447
SMILES and InChIs

SMILES:
S(=O)(=O)(N1CCN(CC1)C)c1cc(c2[nH]c3c(nn(c3c(=O)n2)C)CCC)c(OCC)cc1
Canonical SMILES:
CCCc1nn(c2c1[nH]c(nc2=O)c1cc(ccc1OCC)S(=O)(=O)N1CCN(CC1)C)C
InChI:
InChI=1S/C22H30N6O4S/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29)
InChIKey:
BNRNXUUZRGQAQC-UHFFFAOYSA-N

Cite this record

CBID:88 http://www.chembase.cn/molecule-88.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
5-{2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-7-one
IUPAC Traditional name
revatio
Brand Name
Viagra
Revatio
Synonyms
Sildenafil Citrate
Sildenafil
CAS Number
139755-83-2
PubChem SID
160963551
46508371
PubChem CID
5212

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID
DrugBank DB00203 external link
PubChem 5212 external link
Data Source Data ID Price

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 7.2715216  H Acceptors
H Donor LogD (pH = 5.5) 1.248865 
LogD (pH = 7.4) 1.4989928  Log P 1.6464821 
Molar Refractivity 139.4405 cm3 Polarizability 48.495518 Å3
Polar Surface Area 109.13 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P 2.35  LOG S -3.04 
Solubility (Water) 4.33e-01 g/l 

PROPERTIES

PROPERTIES

Physical Property Bioassay(PubChem)
Solubility
3.5 mg/mL expand Show data source
Hydrophobicity(logP)
1.9 expand Show data source

DETAILS

DETAILS

DrugBank DrugBank
DrugBank - DB00203 external link
Item Information
Drug Groups approved; investigational
Description Sildenfail is a vasoactive agent used to treat erectile dysfunction and reduce symptoms in patients with pulmonary arterial hypertension (PAH). Sildenafil elevates levels of the second messenger, cGMP, by inhibiting its breakdown via phosphodiesterase type 5 (PDE5). PDE5 is found in particularly high concentrations in the corpus cavernosum, erectile tissue of the penis. It is also found in the retina and vascular endothelium. Increased cGMP results in vasodilation which facilitates generation and maintenance of an erection. The vasodilatory effects of sildenafil also help reduce symptoms of PAH.
Indication For the treatment of erectile dysfunction and to relieve symptoms of pulmonary arterial hypertension (PAH).
Pharmacology Erections are controlled by the parasympathetic nervous system. Upon sexual stimulation, a decrease in vascular resistance is mediated by acetylcholine and nitric oxide resulting in vasodilation. The hemodynamic mechanism of an erection is comprised of five stages. During the latent stage, arterial and carvernous smooth muscle relaxation occurs. Vasodilation results in high levels of blood flow causing the penis to grow to its full size. This stage is called tumescence. During the full-erection stage, blood flow fills penis sinusoids and outflow is restricted. This is followed by the rigid-erection phase during which the cavernous muscles contract causing the penis to become rigid. Little blood flow occurs during this stage. During the final stage, detumescence, the cavernous muscles relax and blood flows out of the penis. Erectile dysfunction may occur when there is insufficient blood supply to the penis or when the penis is unable to prevent outflow of blood from the penis. Sildenafil is a specific inhibitor of PDE5, an enzyme responsible for the breakdown of cGMP to 5’-GMP. Increased levels of cGMP stimulate vasodilation and facilitate the generation and maintenance of erections. These vasodilatory effects also help decrease symptoms of PAH. Sildenfail also exhibits some activity against PDE6 (10 times less potentcy compared to PDE5), a PDE isoform found predmoninantly in the retina. This activity is responsible for the blue tinged vision experienced by users of sildenafil.
Affected Organisms
Humans and other mammals
Biotransformation Sildenafil appears to be completely metabolized in the liver to 16 metabolites. Its metabolism is mediated mainly by cytochrome P450 microsomal isozymes 3A4 (major route) and 2C9 (minor route). The major circulating metabolite, N-demethylated metabolite, has PDE selectivity similar to the parent drug and ~50% of its in vitro potency. The N-demethylated metabolite is further metabolized to an N-dealkylated N,N-de-ethylated metabolite. Sildenafil also undergoes N-dealkylation followed by N-demethylation of the piperazine ring.
Absorption >90% absorbed with ~40% reaching systemic circulation unchanged following first-pass metabolism
Half Life 4 hours
Protein Binding 96%
Elimination Sildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose).
Distribution * 105 L
References
Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C: Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996 Jun;8(2):47-52. [Pubmed]
Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM: ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999 Jan;33(1):273-82. [Pubmed]
Fries R, Shariat K, von Wilmowsky H, Bohm M: Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005 Nov 8;112(19):2980-5. [Pubmed]
External Links
Wikipedia
RxList
PDRhealth
Drugs.com

REFERENCES

REFERENCES

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  • • Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C: Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996 Jun;8(2):47-52. Pubmed
  • • Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM: ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999 Jan;33(1):273-82. Pubmed
  • • Fries R, Shariat K, von Wilmowsky H, Bohm M: Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005 Nov 8;112(19):2980-5. Pubmed
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PATENTS

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