Sildenafil citrate
[CAS# 171599-83-0]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism >> PDE inhibitor
• Name: Sildenafil citrate
• Synonyms: 1-[[3-(6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate
• Molecular Formula: C₂₈H₃₈N₆O₁₁S
• Molecular Weight: 666.70
• CAS Registry Number: 171599-83-0
• EC Number: 638-824-3
• SMILES: CCCC1=NN(C2=C1N=C(NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)C)OCC)C.C(C(=O)O)C(CC(=O)O)(C(=O)O)O

Properties

• Solubility: DMSO 23 mg/mL, Water $lessThan$1 mg/mL, Ethanol $lessThan$1 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H320-H335-H412
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Specific target organ toxicity - single exposure	STOT SE	1	H370
Carcinogenicity	Carc.	2	H351
Respiratory sensitization	Resp. Sens.	1	H334
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411

Discovery and Applications

Sildenafil citrate is a synthetic organic compound best known as the active pharmaceutical ingredient in the drug Viagra, developed for the treatment of erectile dysfunction and later approved for pulmonary arterial hypertension under the name Revatio. Chemically, it is the citrate salt of sildenafil, a pyrazolopyrimidinone derivative that acts as a potent and selective inhibitor of phosphodiesterase type 5 (PDE5). Its structure allows it to prevent the degradation of cyclic guanosine monophosphate (cGMP), thereby enhancing nitric oxide–mediated vasodilation in smooth muscle tissue.

The discovery of sildenafil citrate originated in the late 1980s and early 1990s at Pfizer laboratories in the United Kingdom. Initially, the compound was synthesized and studied as a potential treatment for angina pectoris, a condition characterized by reduced blood flow to the heart muscle. During early clinical trials, researchers observed only modest cardiovascular benefits, but participants reported a notable side effect: improved penile erections. This unexpected outcome led Pfizer scientists to redirect their focus, and by 1998, sildenafil citrate was approved by the U.S. Food and Drug Administration as the first oral treatment for erectile dysfunction. Its introduction marked a breakthrough in sexual medicine, offering a discreet, effective, and non-invasive alternative to existing therapies.

Applications of sildenafil citrate extend beyond erectile dysfunction. In 2005, it was also approved for the treatment of pulmonary arterial hypertension, a progressive disease marked by high blood pressure in the arteries of the lungs. By inhibiting PDE5 in pulmonary vascular smooth muscle, sildenafil reduces pulmonary arterial resistance and pressure, improving exercise capacity and delaying disease progression. Research has also investigated its potential use in other conditions such as Raynaud’s phenomenon, altitude sickness, and certain types of heart failure, although these remain secondary or experimental applications.

From a pharmaceutical manufacturing perspective, sildenafil citrate is produced through multi-step organic synthesis, beginning with heterocyclic intermediates that are functionalized to yield the pyrazolopyrimidinone core. The final product is crystallized as a citrate salt to improve stability, solubility, and bioavailability. Its pharmacokinetic profile allows oral administration with predictable absorption, though metabolism by hepatic enzymes, particularly CYP3A4, influences its activity and duration of effect.

The discovery and development of sildenafil citrate exemplify the importance of serendipity in drug research. What began as an attempt to address cardiovascular disease instead led to one of the most commercially successful and socially transformative medications of the late 20th century. Today, sildenafil citrate continues to play a central role in the management of erectile dysfunction and pulmonary arterial hypertension, while ongoing research explores whether its mechanism of action may be harnessed in new therapeutic areas.

References

2003. PDE5 Inhibitor Sildenafil Citrate Augments Endothelium-Dependent Vasodilation in Smokers. Hypertension.
DOI: 10.1161/01.hyp.0000068202.42431.cc

2005. Phosphodiesterase-5 Inhibition With Sildenafil Attenuates Cardiomyocyte Apoptosis and Left Ventricular Dysfunction in a Chronic Model of Doxorubicin Cardiotoxicity. Circulation.
DOI: 10.1161/01.cir.0000160359.49478.c2

2006. Quantitative Determination of Sildenafil Citrate in Herbal Medicinal Formulations by High-Performance Thin-Layer Chromatography. JPC – Journal of Planar Chromatography – Modern TLC.
DOI: 10.1556/jpc.19.2006.6.4

2025. Rapid detection and quantification of falsified Viagra using cloud-based portable NIR technology and machine learning. Journal of Pharmaceutical and Biomedical Analysis.
DOI: 10.1016/j.jpba.2025.116940