36322-90-4 Usage
Uses
Used in Musculoskeletal Diseases:
Piroxicam is used as an anti-inflammatory agent for inflammatory and degenerative diseases of the musculoskeletal system that are accompanied by painful symptoms. It is effective in treating conditions such as rheumatic heart disease, nonspecific infectious polyarthritis, gouty arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, arthrosis, back pain, neuralgia, myalgia, and other diseases associated with inflammation.
Used as a Prostaglandin Synthesis Inhibitor:
Piroxicam is an effective and potent inhibitor of prostaglandin synthesis, acting as a Cox-1 and Cox-2 inhibitor. Studies have shown that Piroxicam blocks the release of platelet ADP and inhibits Cox-1 more potently than Cox-2, making it a valuable drug for managing inflammation and pain.
Used in Clinical Medicine:
As a non-steroidal anti-inflammatory with a long half-life, Piroxicam is a cyclooxygenase inhibitor and a clinically useful NSAID. Its once-daily dosing schedule and extensive hepatic metabolism make it a widely used medication for various inflammatory conditions.
Used in Particular Diseases
Acute Gouty Arthritis:
Dosage and Frequency:?20 mg once daily or 10 mg twice daily
Originator
Amida, Euphoric Pharmaceuticals
Indications
Piroxicam
(Feldene) is indicated for the treatment of rheumatoid
arthritis and osteoarthritis. Piroxicam is a nonspecific
COX inhibitor that has a much higher affinity for
COX-1 than COX-2. This may account for the large
proportion (over 30%) of patients receiving long-term
therapy who have reported side effects.Adverse GI reactions
have been the most frequently reported side effect,
but edema, dizziness, headache, rash, and changes
in hematological parameters have also occurred in 1 to
6% of patients. Piroxicam can cause serious GI bleeding,
ulceration, and perforation, particularly in the elderly, if
the recommended dosage is exceeded or if aspirin is being
taken concurrently.
Manufacturing Process
189.6 g (3.51 mol) of sodium methoxide in 1.4 L of dry dimethylsulfoxide was stirred at room temperature (~ 25°C), while under a dry nitrogen atmosphere. To the stirred slurry, there were then added in one complete portion 300 g (1.17 moles) of methyl 3-oxo-1,2-benzoisothyazolin-2-acetate 1,1-dioxide (Chemische Berichte, vol. 30, p. 1267 (1897)) and flask containing the system was then immediately immersed in an ice-methanol bath. The resulting deep red solution was cooled to 30°C and the ice bath removed. The solution was then stirred under dry nitrogen at 30°C for 4 min, cooled quickly to 18°C and then immediately poured into 4.8 L of 3 N hydrochloric acid solution admixed with ice. The resulting slurry was stirred for 15 min, filtered, then washed with water to give 250 g of crude product. Recrystallization from a chloroform-ethanol mixture (1:1) in the presence of charcoal, then afforded a 61% yield of methyl 3,4-dihydro-4-oxo-2H-1,2benzothiazine-3-carboxylate 1,1-dioxide, melting point 173-174°C after two recrystallizations from isopropanol.A 22 L round-bottomed flask charged with 800 g (3.13 moles) of methyl 3,4dihydro-4-oxo-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide, 3.2 l of water, 9.6 l of 95% ethanol, 673 ml of methyl iodide (1.53 kg, 10.87 moles) and 3.14 L of 1 N aqueous sodium hydroxide. The reaction mixture was then stirred for 30 min at room temperature, under nitrogen atmosphere and then solution was stored for 23 h. The slurry was then chilled at 0°C and filtered. After washing the filter cake twice with water, ethanol and then diethyl ether there were obtained 537 g of methyl 3,4-dihydro-2-methyl-4-oxo-2H-1,2benzothiazine-3-carboxylate 1,1-dioxide, melting point 165°-168°C after recrystallization from 1.25 L of acetonitrile.In 3 L round-bottomed flask there were placed methyl 3,4-dihydro-2-methyl4-oxo-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide, 2-aminopyridin and dry xylene. Nitrogen gas was then bubbled into the suspension for 5 min, then the reaction mixture was heated to begin a period of slow distillation, with complete solution effected during the first 10 min of heating. After 5.5 h, the period of slow distillation was discontinued and reaction mixture was allowed to heat at reflux for approximately 16 h. After that the reaction mixture was cooled to room temperature and filtered. The solid material was crystallized from chloroform with methanol and againe from methanol and then there were obtained piroxicam, melting point 197°-200°C, dec.
Therapeutic Function
Antiinflammatory, Analgesic
Biological Activity
Anti-inflammatory; highly selective inhibitor of COX-1 (ratio of IC 50 values for COX-2/COX-1 ~ 600).
Biochem/physiol Actions
Cyclooxygenase inhibitor.
Clinical Use
NSAID and analgesic
Synthesis
Piroxicam, 1,1-dioxid-4-hydroxy-2-methyl-N-2-pyradyl-2H-1,2-benzothiazine- 3-carboxamide (3.2.78), is synthesized from saccharin (3.2.70). Two methods for saccharin synthesis are described. It usually comes from toluene, which is sulfonated by chlorosulfonic acid, forming isomeric 4- and 2-toluenesulfonyl chlorides. The isomeric products are separated by freezing (chilling). The liquid part, 2-toluenesulfonyl chloride (3.2.68) is separated from the crystallized 4-toluenesulfochloride and reacted with ammonia, giving 2-toluenesulfonylamide (3.2.69). Oxidation of the product with sodium permanganate or chromium (VI) oxide in sulfuric acid gives saccharin—o-sulfobenzoic acid imide (3.2.70).
An alternative way for making saccharin is from methyl ester o-aminobenzoic (anthranylic acid). This undergoes diazotization using nitrous acid, and the resulting diazonium salt (3.2.71) is reacted with sulfur dioxide in the presence of copper dichloride, forming the methyl ester o-sulfobenzoic acid (3.2.72). Reaction of the resulting product with chlorine gives o-chlorosulfonylbenzoic acid methyl ester (3.2.73), which upon reaction with ammonium gives o-sulfonylamidobenzoic acid methyl ester (3.2.74). In the presence of hydrogen chloride, the resulting product undergoes cyclization into saccharin (3.2.70).
Veterinary Drugs and Treatments
In dogs, piroxicam may be beneficial in reducing the pain and inflammation
associated with degenerative joint disease, but there are
safer alternatives available. Its primary use is in dogs as adjunctive
treatment of bladder transitional cell carcinoma. It may also be of
benefit in squamous cell carcinomas, mammary adenocarcinoma,
and transmissible venereal tumor (TVT). There is some use of it
in cats for its anti-tumor effects, but it must be used with extreme
caution in this species.
Drug interactions
Potentially hazardous interactions with other drugs
ACE inhibitors and angiotensin-II antagonists:
antagonism of hypotensive effect; increased risk of
nephrotoxicity and hyperkalaemia. Analgesics: avoid concomitant use of 2 or more
NSAIDs, including aspirin (increased side effects);
avoid with ketorolac (increased risk of side effects
and haemorrhage).
Antibacterials: possibly increased risk of convulsions
with quinolones.
Anticoagulants: effects of coumarins and
phenindione enhanced; possibly increased risk of
bleeding with heparins, dabigatran and edoxaban -
avoid long term use with edoxaban.
Antidepressants: increased risk of bleeding with
SSRIs and venlaflaxine.
Antidiabetic agents: effects of sulphonylureas
enhanced.
Antiepileptics: possibly increased phenytoin
concentration.
Antivirals: increased risk of haematological toxicity
with zidovudine; concentration increased by ritonavir.
Ciclosporin: may potentiate nephrotoxicity.
Cytotoxics: reduced excretion of methotrexate;
increased risk of bleeding with erlotinib.
Diuretics: increased risk of nephrotoxicity;
antagonism of diuretic effect; hyperkalaemia with
potassium-sparing diuretics.
Lithium: excretion decreased.
Pentoxifylline: increased risk of bleeding.
Tacrolimus: increased risk of nephrotoxicity.
Metabolism
Piroxicam metabolism is mainly via cytochrome P450
CYP 2C9 in the liver by hydroxylation of the pyridyl ring
of the piroxicam side-chain, followed by conjugation with
glucuronic acid.
It is excreted mainly in the urine with smaller amounts in
the faeces. Enterohepatic recycling occurs. Less than 5% of
the dose is excreted unchanged in the urine and faeces.
Check Digit Verification of cas no
The CAS Registry Mumber 36322-90-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,6,3,2 and 2 respectively; the second part has 2 digits, 9 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 36322-90:
(7*3)+(6*6)+(5*3)+(4*2)+(3*2)+(2*9)+(1*0)=104
104 % 10 = 4
So 36322-90-4 is a valid CAS Registry Number.
InChI:InChI=1/C15H13N3O4S/c1-18-13(15(20)17-12-8-4-5-9-16-12)14(19)10-6-2-3-7-11(10)23(18,21)22/h2-9,19H,1H3,(H,16,17,20)
36322-90-4Relevant articles and documents
Synthetic method of piroxicam
-
, (2018/10/27)
The invention belongs to the field of chemical synthesis, and more specifically relates to a synthetic method of piroxicam. The synthetic method of piroxicam comprises following steps: 1, sodium saccharin and ethyl chloroacetate are taken as initial raw materials, and condensation reaction is carried out so as to obtain 3-oxo-1,2-benzoisothiazoline-2-methyl acetate-1,1-dioxide; 2, sodium methylateis added into the product in step 1, reaction is carried out under catalytic effect of potassium iodide, and 2-methyl-3,4- dioxo-4-oxo-2H-1,-2- benzothiazine-3-carboxylic acid methyl ester-1, 1-dioxide is obtained under the effect of DMSO; 3, the above product is reacted with 2-aminopyridine at 130 DEG C for 10h so as to obtain a high purity finished product. According to the synthetic method, potassium iodide is taken as a catalyst to increase the reaction conversion rate of step 2 obviously, impurity content is controlled effectively; and the total yield is increased to 69%.
Solid Pharmaceutical Preparations Containing Copolymers Based On Polyethers Combined With Poorly Water-Soluble Polymers
-
, (2012/03/12)
The invention relates to dosage forms which contain preparations of poorly water-soluble substances in a polymer matrix of polyether copolymers, said polyether copolymers being obtained by the radically initiated polymerization of a mixture from 30 to 80% by weight of N-vinyl lactam, 10 to 50% by weight of vinyl acetate and 10 to 50% by weight of a polyether, and at least one poorly water-soluble polymer, the poorly water-soluble substance being present in the polymer matrix as an amorphous substance.
New quaternary ammonium oxicam derivatives targeted toward cartilage: Synthesis, pharmacokinetic studies, and antiinflammatory potency
Nicolas, Colette,Verny, Michel,Giraud, Isabelle,Ollier, Monique,Rapp, Maryse,Maurizis, Jean-Claude,Madelmont, Jean-Claude
, p. 5235 - 5240 (2007/10/03)
Analogues of nonsteroidal antiinflammatory drugs (NSAIDs) oxicams, in which the active group was linked to a quaternary ammonium function [(4- hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide-3-carboxamido)2- methylpyridinium iodide or piroxicam-N+ and [3-(4-hydroxy-2-methyl-2H-1,2- benzothiazine-1,1-dioxide-3-carboxamido)propyl]trimethylammonium iodide or propoxicam-N+] were synthesized. Compounds were labeled with tritium for piroxicam-N+ and carbon-14 for propoxicam-N+. Pharmacokinetic studies conducted on rats showed that these molecules were able to highly concentrate in joint cartilages but their bioavailability by the oral way was low. Only propoxicam-N+ exhibited a sufficient water solubility to be administered intravenously. This molecule was able to restore proteoglycans biosynthesis in cultured articular chondrocytes treated with Interleukin-1β with an efficiency identical to that of indomethacin. These results suggest that the functionalization of oxicam derivatives by a quaternary ammonium group greatly increases their affinity toward articular cartilage without eliminating their pharmacological activity. New drugs synthesized according to this scheme could be useful to obtain a significant decrease of the efficient administered dose and consequently an attenuation of adverse effects such as digestive toxicity.
Topical and transdermal delivery system utilizing submicron oil spheres
-
, (2008/06/13)
The present invention relates to a delivery system which includes a bioactive drug or cosmetic substance presented in the form of submicron oil spheres alone, or drugs or cosmetic substances in a combination with the oil spheres in an aqueous suspension or emulsion. Optionally, a skin penetration enhancer may be included in such formulations. Such preparations achieve improved bioavailability and exert larger pharmacological effects than an equivalent dose of the drug or cosmetic formulated in conventional creams, lotions or oleaginous bases.
Anti-inflammatory analgesic plaster
-
, (2008/06/13)
An anti-inflammatory analgesic plaster carries thereon a base which comprises piroxicam and a polyoxyethylene nonionic surfactant having 5-15 moles of added ethylene oxide.
Reactions of Piroxicam with Alkyl Iodides
Hammen, Philip D.,Berke, Helen,Bordner, Jon,Braisted, Andrew C.,Lombardino, Joseph G.,Whipple, Earl B.
, p. 11 - 16 (2007/10/02)
Alkylation of piroxicam with a homologous series of alkyl iodides gave reversibly formed O-alkyl products 1 as well as unexpected, irreversibly formed zwitterionic compounds 2, alkylated on the pyridine nitrogen, and O,N-bis-alkyl products 3.Proof of structure was accomplished by nmr and X-ray crystal analysis.Product distribution ratios were determined by hplc and are explained by the Hard-Soft Acid-Base principle.
Process for obtaining 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
-
, (2008/06/13)
A process for obtaining 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, which may be used as a non-steroidal analgesic and anti-inflammatory drug. The process comprises reacting saccharin sodium with isopropyl chloroacetate in dimethylformamide, reacting the resultant isopropyl 3-oxo-1,2-benzoisothiazoline-2-acetate 1,1-dioxide with sodium isopropylate in isopropanol to produce an intermediate which, when methylated in an aqueous-alcoholic basic medium with dimethyl sulfate, gives an intermediate compound which when condensed with 2-aminopyridine in xylene, yields 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazone-3-carboxamide 1,1-dioxide.
Pharmaceutical preparation for the therapeutic treatment of rheumatic diseases
-
, (2008/06/13)
Pharmaceutical preparation containing phospholipids for the therapeutic treatment of rheumatic diseases which contain in addition to the antiphlogistically acting oxicam derivatives of the general formula STR1 special 1,2-diacyl-glycero-3-phosphocholines wherein 75-86% by weight of the acyl radicals are unsaturated fatty acid radicals, and the preparation thereof.
Process for the preparation of 3,4-dihydro-2-substituted-2H-1,2-thiazine-carboxylic acid 1,1-dioxide derivatives
-
, (2008/06/13)
Process for the preparation of 3,4-dihydro-2-substituted-4(or 3)-oxo-2H-1,2-thiazine-3(or 4)-carboxylic acid 1,1,-dioxide magnesium chelate derivatives and its acids by reacting appropriately 3,4-dihydro-2-substituted-4(or 3)-oxo-2H-1,2-thiazine 1,1-dixoides with alkylmagnesiumcarbonate and then hydrolyzing and its use as intermediates for the preparation of N-substituted-2-substituted-2H-1,2-thiazine-3(or 4)-carboxamide-1,1-dioxide derivatives, effective antiinflammatory agents.
