China Largest Manufacturer factory sales Allopurinol CAS 315-30-0

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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;PYRIMIDINE;Nucleobases and their analogs;Nucleosides, Nucleotides & Related Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;API's;Other APIs;Miscellaneous Enzyme;Bases & Related Reagents;Nucleotides;ZYLOPRIM;inhibitor 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 form  Powder pka 10.2(at 25℃) color  White or almost white Water Solubility  0.35 g/L (25 ºC) Merck  14,279 InChIKey OFCNXPDARWKPPY-UHFFFAOYSA-N 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  Yes HazardClass  6.1 PackingGroup  III HS Code  29335990 Hazardous Substances Data 315-30-0(Hazardous Substances Data) Toxicity LD50 oral in mouse: 78mg/kg MSDS Information Provider Language 1H-Pyrazolo[3,4-d]pyrimidin-4-ol English ACROS English SigmaAldrich English ALFA English   Allopurinol Usage And Synthesis 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. Indications Allopurinol (Zyloprim) is the drug of choice in the treatment of chronic tophaceous gout and is especially useful in 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°C and 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 was added 3-morpholino-2-cyanoacrylamide (63.4 g) and 85% technical hydrazine hydrate (22.7 g). The mixture was rapidly heated to 95°C and the temperature was maintained at >90°C for 20 minutes. The mixture was then cooled to 60°C and the pH carefully adjusted to 1.5 by the addition of a mixture of sulfuric acid (45.7 g) and ice. The acidified reaction was cooled to 5°C and the crystalline product collected and washed with cold water (2 x 100 ml) 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 and heated to 145°C. The reaction was held at 145°C for 5 hours. The reaction was then cooled to 30°C and the product collected and washed with formamide (2 x 50 ml), water (2 x 150 ml) and acetone (2 x 100 ml). Wt of crude product = 79 g. The crude product was recrystallized by dissolution in a solution made from sodium hydroxide (25 g) in water (1,200 ml) with treatment at 25°C with charcoal (8 g), followed by reprecipitation by the addition of concentrated hydrochloric acid to pH 5. The product was collected and washed with cold water (2 x 300 ml), acetone (2 x 200 ml) and dried in vacuum 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, reduces serum urate levels through a competitive inhibition of uric acid synthesis rather than by impairing renal urate reabsorption. This action is accomplished by inhibiting xanthine oxidase, the enzyme involved in the metabolism of hypoxanthine and xanthine to uric acid. After enzyme inhibition, the urinary and blood concentrations of uric acid are greatly reduced and there is a simultaneous increase in the excretion of the more soluble uric acid precursors, xanthine and hypoxanthine. Allopurinol itself is metabolized by xanthine oxidase to form the active metabolite oxypurinol, which tends to accumulate after chronic administration of the parent drug.This phenomenon contributes to the therapeutic effectiveness of allopurinol in long-term use. Oxypurinol is probably responsible for the antigout effects of allopurinol. Oxypurinol itself is not administered because 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 oral administration, with peak plasma concentrations appearing within 1 hour. Decreases of uric acid can be observed within 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 of chronic tophaceous gout, since patients receiving it show a pronounced decrease in their serum and urinary uric acid levels. Because it does not depend on renal mechanisms for its efficacy, allopurinol is particularly beneficial for patients who already have developed renal uric acid stones, patients with excessively high urate excretion (e.g., above 1,200 mg in 24 hours), patients with a variety of blood disorders (e.g., leukemia, polycythemia vera), patients with excessive tophus deposition, and patients who fail to respond well to the uricosuric drugs. Allopurinol also inhibits reperfusion injury. This injury occurs when organs that either have been transplanted or have had their usual blood perfusion blocked are reperfused with blood or an appropriate buffer solution. The cause of this injury is local formation of free radicals, such as the superoxide anion, the hydroxyl free radical, or peroxynitrite. These substances are strong oxidants and are quite damaging to tissues. Side effects Common toxicities associated with allopurinol administration include a variety of skin rashes, gastrointestinal upset, hepatotoxicity, and fever. These reactions are often sufficiently severe to dictate termination of drug therapy. It is advised that therapy not be initiated during an acute attack of gouty arthritis. As with the uricosuric drugs, therapy with allopurinol should be accompanied both by a sufficient increase in fluid intake to ensure water diuresis and by alkalinization of the urine. Prophylactic use of colchicine also helps to prevent acute attacks of gout that may be brought on during the initial period of allopurinol ingestion. Safety Profile Human poison by ingestion. Poison experimentally by intraperitoneal and subcutaneous routes. An experimental teratogen. Human systemic effects by ingestion: blood leukopenia, dermatitis, jaundice, muscle weakness, thrombocytopenia. When heated to decomposition it emits toxic fumes of NOx. An FDA proprietary drug used as a xanthine oxidase inhibitor. Veterinary Drugs and Treatments The principle veterinary uses for allopurinol are for the prophylactic treatment of recurrent uric acid uroliths and hyperuricosuric calcium oxalate uroliths in small animals. It has also been used in an attempt to treat gout in pet birds and reptiles. Allopurinol has been recommended as an alternative treatment for canine Leishmaniasis. Although it 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 xanthine oxidase. The longer plasma half-life of alloxanthine results in an accumulation in the body during chronic administration, 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

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Leader Biochemical Group is a large leader incorporated industry manufacturers and suppliers of advanced refined raw materials From the year of 1996 when our factory was put into production to year of 2020, our group has successively invested in more than 52 factories with shares and subordinates.We focus on manufacture Pharm & chemicals, functional active ingredients, nutritional Ingredients, health care products, cosmetics, pharmaceutical and refined feed, oil, natural plant ingredients industries to provide top quality of GMP standards products.All the invested factories' product lines cover API and intermediates, vitamins, amino acids, plant extracts, daily chemical products, cosmetics raw materials, nutrition and health care products, food additives, feed additives, essential oil products, fine chemical products and agricultural chemical raw materials And flavors and fragrances. Especially in the field of vitamins, amino acids, pharmaceutical raw materials and cosmetic raw materials, we have more than 20 years of production and sales experience. All products meet the requirements of high international export standards and have been recognized by customers all over the world. Our manufacture basement & R&D center located in National Aerospace Economic & Technical Development Zone Xi`an Shaanxi China. Now not only relying on self-cultivation and development as well as maintains good cooperative relations with many famous research institutes and universities in China. Now, we have closely cooperation with Shanghai Institute of Organic Chemistry of Chinese Academy of Science, Beijing Institute of Material Medical of Chinese Academy of Medical Science, China Pharmaceutical University, Zhejiang University. Closely cooperation with them not only integrating Science and technology resources, but also increasing the R&D speed and improving our R&D power. Offering Powerful Tech supporting Platform for group development. Keep serve the manufacture and the market as the R&D central task, focus on the technical research.  Now there are 3 technology R & D platforms including biological extract, microorganism fermentation and chemical synthesis, and can independently research and develop kinds of difficult APIs and pharmaceutical intermediates. With the strong support of China State Institute of Pharmaceutical Industry (hereinafter short for CSIPI), earlier known as Shanghai Institute of Pharmaceutical Industry (SIPI), we have unique advantages in the R & D and industrialization of high-grade, precision and advanced products.  Now our Group technical force is abundant, existing staff more that 1000 people, senior professional and technical staff accounted for more than 50% of the total number of employees, including 15 PhD research and development personnel, 5 master′ S degree in technical and management personnel 9 people. We have advanced equipment like fermentation equipment and technology also extraction, isolation, purification, synthesis with rich production experience and strict quality control system, According to the GMP required, quickly transforming the R&D results to industrial production in time, it is our advantages and our products are exported to North and South America, Europe, Middle East, Africa, and other five continents and scale the forefront in the nation, won good international reputation.  We believe only good quality can bring good cooperation, quality is our key spirit during our production, we are warmly welcome clients and partner from all over the world contact us for everlasting cooperation, Leader will be your strong, sincere and reliable partner in China.

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