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| | Meloxicam Chemical Properties |
| Melting point | 255 °C | | density | 1.613±0.06 g/cm3(Predicted) | | storage temp. | 2-8°C | | solubility | DMSO: soluble | | pka | 4.08 in water; 4.24 ± 0.01 in water/ethanol (1:1); 4.63 ± 0.03 in water/ethanol (1:4) | | form | Off-white solid | | color | yellow | | Water Solubility | practically insoluble in water(0.154 mg/mL), with higher solubility observed in strong acids and bases. | | Merck | 14,5826 | | BCS Class | 2(CLogP),
4 (LogP) | | Stability: | Stable. Incompatible with strong oxidizing agents. | | InChI | InChI=1S/C14H13N3O4S2/c1-8-7-15-14(22-8)16-13(19)11-12(18)9-5-3-4-6-10(9)23(20,21)17(11)2/h3-7,18H,1-2H3,(H,15,16,19) | | InChIKey | ZRVUJXDFFKFLMG-UHFFFAOYSA-N | | SMILES | S1(=O)(=O)C2=CC=CC=C2C(O)=C(C(NC2=NC=C(C)S2)=O)N1C | | EPA Substance Registry System | 2H-1,2-Benzothiazine-3-carboxamide, 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-, 1,1-dioxide (71125-38-7) |
| | Meloxicam Usage And Synthesis |
| Description | Known as a nonsteroidal anti-inflammatory drug (NSAID), Meloxicam is commonly used to treat pain or inflammation caused by rheumatoid arthritis and osteoarthritis in adults. It is also used to treat juvenile rheumatoid arthritis in children who are at least 2 years old. It is effective to reduce pain, inflammation, swelling, and stiffness of the joints. Developed by Boehringer-Ingelheim, Meloxicam is a derivative of oxicam that can relieve the symptoms of arthritis, primary dysmenorrhea, fever with analgesic and antipyretic properties. Meloxicam was approved for use in April 2000.
Anti-inflammatory effects of meloxicam function by inhibiting the prostaglandin synthetase (cyclooxygenase 1 and 2) which results in a decrease of the synthesis of prostaglandins. As prostaglandins are chemicals that contribute to inflammation especially within joints, which leads to the common symptoms of pain, tenderness, and swelling associated with arthritis, inhibition of their synthesis can be associated with the analgesic and antipyretic effects of meloxicam. As a result, inflammation and its accompanying symptoms are reduced. Meloxicam starts to relieve pain about 30 to 60 minutes after administration.
| | References | https://en.wikipedia.org/wiki/Meloxicam
https://www.drugbank.ca/drugs/DB00814
https://www.drugs.com/meloxicam.html
http://www.medicinenet.com/meloxicam/article.htm
| | Description | Mobec was launched in Columbia, Denmark, France, Germany, Ireland,
Italy, Netherlands, S. Africa, Sweden, and the UK for osteo- and rheumatoid arthritis
as an NSAID. It can be synthesized in four steps from benzisothiazolo-3(2H)-one-
1,1-dioxide. By shutting down prostaglandin synthesis, it has antiinflammatory,
antipyretic and analgesic properties. This is accomplished by preferentially inhibiting
the COX-2 system relative to the COX-I which also leads to an improved GI safety
profile relative to naproxen, diclofenac and prioxicam. It can also interfere with
neutrophil function like degranulation. Meloxicam did not inhibit proteoglycan
synthesis in osteroarthitic cartilage or chondrocytes and had no effect on platelet
aggregation. It is metabolized by the P450 2C9 system into four metabolites which
are all inactive. | | Description | Viramune was launched in the US for use in combination with nucleoside
analogs to treat HIV-infected adults who have experienced clinical and/or immulogic
deterioration. It can be prepared in four steps from 2chloro-4-methyl-3-nitropyridine.
It is a potent inhibitor of HIV-1 reverse transcriptase with no rnuscarinic or
benzodiazepine activity. Mechanistically, it is a non-competitive non-nucleoside
inhibitor. It has a low toxicity for uninfected cells most likely due to its specificity, i.e.,
it does not inhibit eukaryotic DNA polymerase α, β, γ and δ. HIV-2, SIV and FeLV are
not affected by nevirapine and monotherapy is limited by the rapid onset of
resistance. | | Description | Meloxicam is a selective inhibitor of COX-2 (IC50s = 11.8 and 143 μM for COX-2 and COX-1, respectively, in an enzyme activity assay) and a non-steroidal anti-inflammatory drug (NSAID). Meloxicam (0.03%) reduces croton oil-induced increases in TNF-α and IL-1β mRNA levels and increases IL-10 mRNA levels in cornea in a rabbit model of acute ocular inflammation. It inhibits pleural plasma exudation in a carrageenan-induced rat model of pleurisy when administered at a dose of 3 mg/kg. In a canine model of unilateral osteoarthritis of the right stifle joint, meloxicam reduces prostaglandin E2 (PGE2) levels in plasma and right stifle joint synovial fluid when administered at a dose of 0.2 mg/kg. Formulations containing meloxicam have been used in the treatment of osteoarthritis and rheumatoid arthritis. | | Chemical Properties | Light Yellow Solid | | Originator | Boehringer Ingelheim (Germany) | | Originator | Boehringer lngelheim (Germany) | | Uses | Preferential cyclooxygenase (COX-2) inhibitor. Sudoxicam and Meloxicam are nonsteroidal anti-inflammatory drugs (NSAIDs) from the enol-carboxamide class. | | Uses | angiotensin 2 receptor antagonist | | Uses | For symptomatic treatment of arthritis and osteoarthritis. | | Uses | An inhibitor of Cox-1 and Cox-2, selective for Cox-2. | | Uses | Preferential cyclooxygenase (COX-2) inhibitor. Used as an anti-inflammatory. | | Definition | ChEBI: A benzothiazine that is piroxicam in which the pyridin-2-yl group is replaced by a 5-methyl-1,3-thiazol-2-yl group. A non-steroidal anti-inflammatory drug and selective inhibitor of COX-2, it is used particularly for the management of rheumatoid arthritis. | | Indications | Meloxicam (Mobic), recently introduced for the
treatment of osteoarthritis, is also used for rheumatoid
arthritis and certain acute conditions. Although meloxicam
is sometimes reported to be a selective COX-2 inhibitor,
it is considerably less selective than celecoxib or
rofecoxib. Its adverse effects are similar to those of
piroxicam and other NSAIDs; however, the frequency
of GI side effects is lower for meloxicam than for piroxicam
and several other NSAIDs. | | Manufacturing Process | A mixture of 26.9 g (0.1 mol) of the 1,1-dioxide of methyl 4-hydroxy-2- methyl-2H-1,2-benzothiazine-3-carboxylate and 12.5 g (0.11 mol) of 2- amino-5-methylthiazole was refluxed in 4 liters of xylene for 24 hours in a nitrogen atmosphere. The methanol formed by the reaction was removed by means of a 4-A-molecular sieve mounted in a Soxhlet-extractor. The hot reaction solution was filtered. Upon cooling and standing overnight, the crude product separated out of the filtrate in the form of crystals (32.0 g, 91% of theory). After recrystallization from ethylene chloride 26.0 g (74% of theory) of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3- carboxamide-1,1-dioxide were obtained; M.P.: 254°C (decomp.). | | Brand name | Mobic
(Boehringer Ingelheim). | | Therapeutic Function | Antiinflammatory | | General Description | Meloxicam (Mobic) is a selective COX-2 inhibitor amongoxicams indicated for use in RA and OA. It also has a relativelylong half-life of 15 to 20 hours and has a much lowerrate of serious GI side effects and a lower than average riskof nephropathy when compared with other conventionalNSAIDs.196 The recommended dose is 7.5 mg once dailywith a maximum of 15 mg/d. Meloxicam is metabolized inhumans mainly by CYP2C9 (with a minor contribution viaCYP3A4) to 5'-hydroxymethylmeloxicam and 5 carboxymeloxicam.
In large-scale comparative trials, meloxicam was foundto be at least as effective as most conventional NSAIDs inthe treatment of rheumatic disease or postoperative pain, buthas demonstrated a more favorable GI tolerability profile. | | Clinical Use | In April 2000, the U.S. FDA approved meloxicam for the treatment of osteoarthritis. When meloxicam was initially introduced in the United Kingdom, it was promoted as a selective COX-2 inhibitor. | | Veterinary Drugs and Treatments | Meloxicam is principally used for the symptomatic treatment of osteoarthritis
in dogs. Short-term (single dose injectable) use is also
approved (in the USA) for cats for the control of postoperative pain
and inflammation associated with orthopedic surgery, ovariohysterectomy
and castration when administered prior to surgery. | | Metabolism | Meloxicam, however, is less
selective than celecoxib and much less selective than rofecoxib in in vitro studies.
Meloxicam is readily absorbed when administered orally and is highly bound to plasma proteins. Meloxicam is
extensively metabolized in the liver, primarily by CYP2C9 and, to a lesser extent, by CYP3A4. The advantages of
meloxicam over celecoxib and rofecoxib in the treatment of osteoarthritis (or rheumatoid arthritis) are not readily
apparent. |
| | Meloxicam Preparation Products And Raw materials |
| Raw materials | thiazine-->2-Amino-5-methylthiazole-->D-Glucitol, 1-deoxy-1-(methylamino)-, compd. with 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (1:1)-->2H-1,2-Benzothiazine-3-carboxamide, 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-, 1,1-dioxide, potassium salt, hydrate (1:1:1)-->methyl 3-oxo1,2-benzisothiazole-2(3H)-acetate 1,1-dioxide-->Despyridyl Piroxicam (Piroxicam Impurity C)-->Methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide-->Ethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide |
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