Allopurinol CAS 315-30-0
Introduction：Basic information about Allopurinol CAS 315-30-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Allopurinol Basic information
| Product Name: | Allopurinol |
| Synonyms: | Hydroxypyrazolodpyrimidine;pyrazolo(3,4-d)pyrimidin-1-ol;AllopurinolBp2001;4-Oxopyrazolo[3,4-d]pyrimidine;NSC 101655;ALLOPURINOL,USP;1,5-DIHYDRO-4H-PYRAZOLO[3,4-D]PYRIMIDIN-4-ONE(ALLOPURINOL);ALLOPURINOL(P) |
| CAS: | 315-30-0 |
| MF: | C5H4N4O |
| MW: | 136.11 |
| EINECS: | 206-250-9 |
| Product Categories: | Miscellaneous Natural Products;Fused Ring Systems;Heterocyclic Compounds;Antitumors for Research and Experimental Use;Chemical Reagents for Pharmacology Research;Biochemistry;Nucleobases and their analogs;Nucleosides, Nucleotides & Related Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;PYRIMIDINE;API's;Other APIs;ZYLOPRIM;inhibitor;Miscellaneous Enzyme;Bases & Related Reagents;Nucleotides;315-30-0;john's |
| Mol File: | 315-30-0.mol |
Allopurinol Chemical Properties
| Melting point | >300 °C (lit.) |
| Boiling point | 250.36°C (rough estimate) |
| density | 1.4295 (rough estimate) |
| refractive index | 1.8500 (estimate) |
| storage temp. | 15-25°C |
| solubility | 1 M NaOH: soluble50mg/mL, clear to very slightly hazy, colorless to faintly yellow |
| pka | 10.2(at 25℃) |
| form | Powder |
| color | White or almost white |
| biological source | synthetic (organic) |
| Water Solubility | 0.35 g/L (25 ºC) |
| Merck | 14,279 |
| BCS Class | 3,1 |
| Major Application | pharmaceutical (small molecule) |
| InChI | 1S/C5H4N4O/c10-5-3-1-8-9-4(3)6-2-7-5/h1-2H,(H2,6,7,8,9,10) |
| InChIKey | OFCNXPDARWKPPY-UHFFFAOYSA-N |
| SMILES | O=C1NC=Nc2[nH]ncc12 |
| CAS DataBase Reference | 315-30-0(CAS DataBase Reference) |
| NIST Chemistry Reference | Allopurinol(315-30-0) |
| EPA Substance Registry System | Allopurinol (315-30-0) |
Safety Information
| Hazard Codes | T,Xi,Xn |
| Risk Statements | 25-43-36/37/38-20/21/22 |
| Safety Statements | 28-36/37-45-36/37/39-26-24-36 |
| RIDADR | UN 2811 6.1/PG 3 |
| WGK Germany | 2 |
| RTECS | UR0785000 |
| TSCA | TSCA listed |
| HazardClass | 6.1 |
| PackingGroup | III |
| HS Code | 29335990 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 3 Oral Skin Sens. 1 |
| Hazardous Substances Data | 315-30-0(Hazardous Substances Data) |
| Toxicity | LD50 oral in mouse: 78mg/kg |
| Chemical Properties | White to Off-White Solid |
| Originator | Zyloprim ,Burroughs-Wellcome ,US ,1966 |
| Uses | Xanthine oxidase inhibitor; decreases uric acid production. Used in treatment of hyperuricemia and chronic gout. Antiurolithic |
| Uses | antihyperuricemia, antigout, antiurolithic |
| Uses | Allopurinol does not reduce serum uric acid levels by increasing renal uric acid excretion; instead it lowers plasma urate levels by inhibiting the final steps in uric acid biosynthesis. Uric acid in humans is formed primarily by xanthine oxidase-catalyzed oxidation of hypoxanthine and xanthine to uric acid. Allopurinol (8) and its primary metabolite, alloxanthine (9) [CAS: 2465-59-0], are inhibitors of xanthine oxidase. Inhibition of the last two steps in uric acid biosynthesis by blocking xanthine oxidase reduces the plasma concentration and urinary excretion of uric acid and increases the plasma levels and renal excretion of the more soluble oxypurine precursors. Normally, in humans the urinary purine content is almost solely uric acid; treatment with allopurinol results in the urinary excretion of hypoxanthine, xanthine, and uric acid, each with its independent solubility. Lowering the uric acid concentration in plasma below its limit of solubility facilitates the dissolution of uric acid deposits. The effectiveness of allopurinol in the treatment of gout and hyperuricemia that results from hematogical disorders and antineoplastic therapy has been demonstrated. |
| Definition | ChEBI: Allopurinol is a bicyclic structure comprising a pyrazole ring fused to a hydroxy-substituted pyrimidine ring. It has a role as a radical scavenger, a gout suppressant, an antimetabolite and an EC 1.17.3.2 (xanthine oxidase) inhibitor. It is an organic heterobicyclic compound and a nucleobase analogue. It derives from a hydride of a 1H-pyrazolo[4,3-d]pyrimidine. |
| Indications | Allopurinol (Zyloprim) is the drug of choice in the treatmentof chronic tophaceous gout and is especially usefulin patients whose treatment is complicated by renal insufficiency. |
| Manufacturing Process | 3-Morpholino-2-cyanoacrylamide: A stirred mixture of cyanoacetamide (63 g),triethylorthoformate (134 g), morpholine (82.5 g) and acetonitrile (37.5 ml)was heated under reflux for 4 hours. The initial reflux temperature was 117°Cand the final reflux temperature was 82°C. At the end of the reflux period the mixture was cooled to 30°C and the heavy crystalline precipitate was collected and washed with 2 x 75 ml of ethanol.The product was dried in vacuum at 30°C. Wt = 111 g. Yield = 82%, MP 173-175°C. 3-Aminopyrazole-4-carbxamide hemisulfate: To water (253 ml) at 60°C wasadded 3-morpholino-2-cyanoacrylamide (63.4 g) and 85% technical hydrazinehydrate (22.7 g). The mixture was rapidly heated to 95°C and thetemperature was maintained at >90°C for 20 minutes. The mixture was thencooled to 60°C and the pH carefully adjusted to 1.5 by the addition of amixture of sulfuric acid (45.7 g) and ice. The acidified reaction was cooled to5°C and the crystalline product collected and washed with cold water (2 x 100ml) and acetone (2 x 50 ml). The product was dried in vacuum at 80°C. Wt=5.8 g. Yield =95%, MP 237-239°C. 4-Hydroxypyrazolo[3,4-d]pyrimidine: A suspension of 3-aminopyrazole-4-carboxamide hemisulfate (113 g) in formamide (325 g) was stirred andheated to 145°C. The reaction was held at 145°C for 5 hours. The reactionwas then cooled to 30°C and the product collected and washed withformamide (2 x 50 ml), water (2 x 150 ml) and acetone (2 x 100 ml). Wt ofcrude product = 79 g. The crude product was recrystallized by dissolution in asolution made from sodium hydroxide (25 g) in water (1,200 ml) withtreatment at 25°C with charcoal (8 g), followed by reprecipitation by theaddition of concentrated hydrochloric acid to pH 5. The product was collectedand washed with cold water (2 x 300 ml), acetone (2 x 200 ml) and dried invacuum at 60°C. Wt = 70 g. Yield = 80%. |
| Brand name | Lopurin(Abbott); Lopurin (BASF); Zyloprim (Promethus). |
| Therapeutic Function | Xanthine oxidase inhibitor, Gout therapy |
| General Description | Odorless tasteless white microcrystalline powder. |
| Air & Water Reactions | Insoluble in water. |
| Reactivity Profile | Allopurinol is an aminoalcohol. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. Allopurinol darkens above 572° F, and at an indefinite high temperature, Allopurinol chars and decomposes. At 221° F, maximum stability occurs at pH 3.1- 3.4. Allopurinol decomposes in acidic and basic solutions. |
| Fire Hazard | Flash point data for Allopurinol are not available; however, Allopurinol is probably combustible. |
| Biochem/physiol Actions | Inhibitor of xanthine oxidase and de novo pyrimidine biosynthesis. A classical agent in treatment of hyperuricemia and gout. |
| Mechanism of action | Allopurinol, in contrast to the uricosuric drugs, reducesserum urate levels through a competitive inhibition ofuric acid synthesis rather than by impairing renal uratereabsorption. This action is accomplished by inhibitingxanthine oxidase, the enzyme involved in the metabolismof hypoxanthine and xanthine to uric acid. Afterenzyme inhibition, the urinary and blood concentrationsof uric acid are greatly reduced and there is a simultaneousincrease in the excretion of the more solubleuric acid precursors, xanthine and hypoxanthine. Allopurinol itself is metabolized by xanthine oxidaseto form the active metabolite oxypurinol, whichtends to accumulate after chronic administration of theparent drug.This phenomenon contributes to the therapeuticeffectiveness of allopurinol in long-term use.Oxypurinol is probably responsible for the antigout effectsof allopurinol. Oxypurinol itself is not administeredbecause it is not well absorbed orally. |
| Pharmacokinetics | Allopurinol was synthesized in 1956 as part of a study of purine antagonists. It is well absorbed on oraladministration, with peak plasma concentrations appearing within 1 hour. Decreases of uric acid can be observedwithin 24 to 48 hours. Excretion of allopurinol and its metabolite occurs primarily in the urine, with approximately 20%of a dose being excreted in the feces. |
| Clinical Use | Allopurinol is especially indicated in the treatment ofchronic tophaceous gout, since patients receiving it showa pronounced decrease in their serum and urinary uricacid levels. Because it does not depend on renal mechanismsfor its efficacy, allopurinol is particularly beneficialfor patients who already have developed renal uric acidstones, patients with excessively high urate excretion(e.g., above 1,200 mg in 24 hours), patients with a varietyof blood disorders (e.g., leukemia, polycythemia vera),patients with excessive tophus deposition, and patientswho fail to respond well to the uricosuric drugs. Allopurinol also inhibits reperfusion injury. This injuryoccurs when organs that either have been transplantedor have had their usual blood perfusion blockedare reperfused with blood or an appropriate buffer solution.The cause of this injury is local formation of freeradicals, such as the superoxide anion, the hydroxyl freeradical, or peroxynitrite. These substances are strongoxidants and are quite damaging to tissues. |
| Side effects | Common toxicities associated with allopurinol administrationinclude a variety of skin rashes, gastrointestinalupset, hepatotoxicity, and fever. These reactions are oftensufficiently severe to dictate termination of drugtherapy. It is advised that therapy not be initiated duringan acute attack of gouty arthritis. As with the uricosuricdrugs, therapy with allopurinol should be accompaniedboth by a sufficient increase in fluid intake toensure water diuresis and by alkalinization of the urine.Prophylactic use of colchicine also helps to preventacute attacks of gout that may be brought on during theinitial period of allopurinol ingestion. |
| Safety Profile | Human poison byingestion. Poison experimentally byintraperitoneal and subcutaneous routes. Anexperimental teratogen. Human systemiceffects by ingestion: blood leukopenia,dermatitis, jaundice, muscle weakness,thrombocytopenia. When heated todecomposition it emits toxic fumes of NOx.An FDA proprietary drug used as a xanthineoxidase inhibitor. |
| Veterinary Drugs and Treatments | The principle veterinary uses for allopurinol are for the prophylactictreatment of recurrent uric acid uroliths and hyperuricosuric calciumoxalate uroliths in small animals. It has also been used in anattempt to treat gout in pet birds and reptiles. Allopurinol has been recommended as an alternative treatmentfor canine Leishmaniasis. Althoughit appears to have clinical efficacy,it does not apparently clear the parasite in most dogs at usual dosages.Allopurinol may also be useful for American Trypanosomiasis. |
| Drug interactions | Potentially hazardous interactions with other drugs ACE inhibitors: increased risk of toxicity with captopril. Antivirals: concentration of didanosine increased - avoid. Ciclosporin: isolated reports of raised ciclosporin levels (risk of nephrotoxicity). Cytotoxics: effects of azathioprine and mercaptopurine enhanced with increased toxicity; avoid with capecitabine and ideally azathioprine. |
| Metabolism | Allopurinol is rapidly metabolized via oxidation and the formation of numerous ribonucleoside derivatives. The major oxidation metabolite, alloxanthine or oxypurinol, has a much longer half-life(18–30 hours versus 2–3 hours) than the parent drug and is an effective, although less potent, inhibitor of xanthineoxidase. The longer plasma half-life of alloxanthine results in an accumulation in the body during chronicadministration, thus contributing significantly to the overall therapeutic effects of allopurinol. |
| Precautions | Since allopurinol is metabolized by the hepatic microsomaldrug-metabolizing enzymes, coadministration ofdrugs also metabolized by this system should be donewith caution. Because allopurinol inhibits the oxidationof mercaptopurine and azathioprine, their individualadministered doses must be decreased by as much as75% when they are given together with allopurinol.Allopurinol may also increase the toxicity of other cytotoxicdrugs (e.g., vidarabine). The actions of allopurinolare not antagonized by the coadministration of salicylates. |
Allopurinol Preparation Products And Raw materials
| Raw materials | Hydrazinium hydroxide solution-->Ethyl cyanoacetate-->2-Cyanoacetamide-->Ethyl (ethoxymethylene)cyanoacetate-->Ethyl 3-amino-4-pyrazolecarboxylate-->Morpholine-->Hydrazine hydrate-->Triethyl orthoformate |
| Preparation Products | 1H-Pyrazolo[3,4-d]pyrimidin-4-amine, N-methyl- (9CI) |
