Allopurinol
[CAS# 315-30-0]

Identification

• Classification: API >> Antipyretic analgesics >> Anti-gout medicine
• Name: Allopurinol
• Synonyms: 4-Hydroxypyrazolo[3,4-d]pyrimidine; 1H-Pyrazolo[3,4-d]pyrimidin-4-ol; HPP
• Molecular Formula: C₅H₄N₄O
• Molecular Weight: 136.11
• CAS Registry Number: 315-30-0
• EC Number: 206-250-9
• SMILES: C1=NNC2=C1C(=O)NC=N2

Properties

• Density: 1.7±0.1 g/cm³ Calc.^*
• Melting point: 384 °C (Expl.), 384 °C (Expl.)
• Solubility: DMSO: 27 mg/mL (Expl.), DMSO: 27 mg/mL, water: 0.35 g/L (25 °C) (Expl.)
• Index of refraction: 1.816 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H301-H317
• Safety Statements: P261-P264-P270-P272-P280-P301+P316-P302+P352-P321-P330-P333+P317-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin sensitization	Skin Sens.	1	H317
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Reproductive toxicity	Lact.	-	H362
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Reproductive toxicity	Repr.	1A	H360
Skin irritation	Skin Irrit.	2	H315
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - single exposure	STOT SE	3	H335
Reproductive toxicity	Repr.	1B	H360
Eye irritation	Eye Irrit.	2	H319
Skin sensitization	Skin Sens.	1A	H317
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Specific target organ toxicity - repeated exposure	STOT RE	2	H373

• Transport Information: UN 2811

Discovery and Applications

Allopurinol is a pharmaceutical compound primarily used as a xanthine oxidase inhibitor to manage hyperuricemia and prevent gout attacks. Chemically, it is a structural analogue of hypoxanthine and belongs to the class of purine derivatives. Allopurinol functions by inhibiting xanthine oxidase, the enzyme responsible for converting hypoxanthine and xanthine into uric acid, thus reducing serum and urinary uric acid levels.

The discovery of allopurinol dates back to the early 1960s when it was developed as a treatment for gout and other diseases associated with excess uric acid production. The compound's efficacy in decreasing uric acid levels made it a significant advancement over previous therapies, as it directly targets the enzyme catalyzing uric acid formation rather than merely increasing uric acid excretion.

Pharmacologically, allopurinol undergoes conversion in the body to oxypurinol (alloxanthine), an active metabolite that also inhibits xanthine oxidase, contributing to its therapeutic effects. The drug is administered orally, absorbed well from the gastrointestinal tract, and excreted primarily via the kidneys.

Clinically, allopurinol is widely prescribed for the prevention of gout flares, management of uric acid nephrolithiasis, and to reduce uric acid levels in patients undergoing chemotherapy or radiotherapy, where rapid cell turnover may elevate uric acid. It is also used in conditions such as Lesch-Nyhan syndrome and certain types of kidney stones.

The compound’s mechanism involves competitive inhibition of xanthine oxidase, which decreases the production of uric acid and reduces the formation of urate crystals that cause gout symptoms. This enzymatic inhibition also helps prevent renal damage caused by uric acid accumulation.

Allopurinol’s safety profile has been well-established through decades of clinical use. Common side effects include rash and gastrointestinal discomfort, whereas rare but severe adverse reactions involve hypersensitivity syndromes. Dose adjustments are necessary in patients with renal impairment to prevent toxicity.

Analytical characterization of allopurinol involves nuclear magnetic resonance (¹H and ¹³C NMR) spectroscopy confirming its purine structure, infrared (IR) spectroscopy displaying characteristic functional group vibrations such as amine and imidazole ring stretches, and mass spectrometry validating molecular weight.

Physically, allopurinol is a white to off-white crystalline powder, soluble in slightly alkaline aqueous solutions but sparingly soluble in water and organic solvents. Its chemical stability allows for various formulation types including tablets and injectable preparations.

In summary, allopurinol is a purine analog xanthine oxidase inhibitor widely used to manage hyperuricemia and prevent gout by reducing uric acid synthesis. Its discovery marked an important advancement in gout treatment, and its clinical applications have since expanded to include other hyperuricemia-related conditions.

References

1979. Behavior of N-methylated allopurinols and related 4-thioxopyrazolo [3,4-d]pyrimidines towards bovine milk xanthine oxidase. Biochimica et Biophysica Acta (BBA) - Enzymology, 568(2).
DOI: 10.1016/0005-2744(79)90217-1

1979. Effect of allopurinol (Zyloric) on patients undergoing open heart surgery. Japanese Circulation Journal, 43(5).
DOI: 10.1253/jcj.43.395

1979. Kidney stone disease: evaluation and medical management. Postgraduate Medicine, 66(4).
DOI: 10.1080/00325481.1979.11715275