71125-38-7

Basic information

• Product Name: Meloxicam
• Synonyms: 2H-1,2-benzothiazine-3-carboxamide, 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-, 1,1-dioxide, sodium salt (1:1); Sodium 2-methyl-3-[(5-methyl-1,3-thiazol-2-yl)carbamoyl]-2H-1,2-benzothiazin-4-olate 1,1-dioxide; 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide; 4-HYDROXY-2-METHYL-N-(5-METHYL-2-THIAZOLYL)-2H-1,2-BENZOTHIAZINE-3-CARBOXAMIDE 1,1-DIOXIDE
• CAS NO: 71125-38-7
• Molecular Formula: C₁₄H₁₃N₃O₄S₂
• Molecular Weight: 351.4007
• EINECS: 615-253-8
• Product Categories: Other APIs;AVAPRO;Lipid signaling;API's;Active Pharmaceutical Ingredients;API;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Health & Beauty
• Mol File: 71125-38-7.mol

Chemical Properties

• Melting Point: 255 °C
• Density: 1.614g/cm³
• Refractive Index: 1.72
• Storage Temp.: 0-6°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)
• Water Solubility: Soluble in water (22 mg/ml), DMSO (25 mg/ml), DMF, acetone(slightly soluble), ethanol(slightly soluble), and methanol(slightly soluble).
• Stability: Stable. Incompatible with strong oxidizing agents.
• Merck: 14,5826
• CAS DataBase Reference: Meloxicam(CAS DataBase Reference)
• NIST Chemistry Reference: Meloxicam(71125-38-7)
• EPA Substance Registry System: Meloxicam(71125-38-7)

Safety Data

• Hazard Codes: Xn,T
• Statements: 22-36/37/38-25
• Safety Statements: 26-45-60-36/37
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: DL0702000
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 71125-38-7(Hazardous Substances Data)

Usage

Uses

1. Used in Pharmaceutical Industry:
Meloxicam is used as an anti-inflammatory agent for the symptomatic treatment of arthritis and osteoarthritis. It functions by inhibiting prostaglandin synthetase (cyclooxygenase 1 and 2), leading to a decrease in the synthesis of prostaglandins, which are chemicals that contribute to inflammation, particularly within joints.
2. Used in Pharmaceutical Industry as a Preferential COX-2 Inhibitor:
Meloxicam is used as a preferential cyclooxygenase (COX-2) inhibitor, which results in an improved gastrointestinal safety profile compared to other NSAIDs such as naproxen, diclofenac, and prioxicam.
3. Used in Pharmaceutical Industry as an Angiotensin 2 Receptor Antagonist:
Meloxicam is also used as an angiotensin 2 receptor antagonist, which may contribute to its anti-inflammatory effects.
4. Used in Veterinary Medicine:
Meloxicam formulations have been used in the treatment of osteoarthritis and rheumatoid arthritis in animals, such as in a canine model of unilateral osteoarthritis of the right stifle joint.
5. Used in Ophthalmology:
Meloxicam (0.03%) has been shown to reduce croton oil-induced increases in TNF-α and IL-1β mRNA levels and increase IL-10 mRNA levels in the cornea in a rabbit model of acute ocular inflammation.

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

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.).

Therapeutic Function

Antiinflammatory

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.

Synthetic route

meloxicam potassium salt monohydrate (892395-40-3) → meloxicam (71125-38-7)

Conditions	Yield
Stage #1: meloxicam potassium salt monohydrate With potassium hydroxide; pyrographite In ethanol; water at 40 - 45℃; for 0.666667h; Stage #2: With acetic acid In ethanol; water at 10 - 30℃; for 2.5h; pH=3 - 5; Product distribution / selectivity;	98.5%
Stage #1: meloxicam potassium salt monohydrate With potassium hydroxide; pyrographite In ethanol; water at 40 - 45℃; for 0.666667h; Stage #2: With hydrogenchloride In ethanol; water at 10 - 30℃; for 2.5h; pH=3 - 5; Product distribution / selectivity;	97.1%
Stage #1: meloxicam potassium salt monohydrate With potassium hydroxide In ethanol; water at 50 - 55℃; Large scale reaction; Stage #2: With hydrogenchloride In ethanol; water at 65 - 70℃; Reflux; Large scale reaction;	91%

5-methyl-2-thiazol-2-amine (7305-71-7) + ethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (24683-26-9) → meloxicam (71125-38-7)

Conditions	Yield
In o-xylene for 24h; Product distribution / selectivity; Heating / reflux;	95%
In xylene at 139 - 140℃; for 32 - 37h; Product distribution / selectivity; Heating / reflux; Molecular sieve;	92.48%

5-methyl-2-thiazol-2-amine (7305-71-7) + methyl 2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (35511-15-0) → meloxicam (71125-38-7)

Conditions	Yield
In o-xylene at 25 - 145℃; for 33.5 - 38h; Industry scale;	88.8%
In xylene for 48h; Heating;

N-methylglucamine salt of meloxicam (244241-52-9) → meloxicam (71125-38-7)

Conditions	Yield
Stage #1: N-methylglucamine salt of meloxicam In water at 70℃; for 0.5h; CN1 carbon; Stage #2: With water; acetic acid at 70℃; for 0.25h; pH=4.6; Product distribution / selectivity;	87%

5-methyl-2-thiazol-2-amine (7305-71-7) + ethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (24683-26-9) + 1,2-dichloro-benzene (95-50-1) → meloxicam (71125-38-7)

Conditions	Yield
With 1,2-dichloro-ethane	76%

5-methyl-2-thiazol-2-amine (7305-71-7) + 4-hydroxy-2-methyl-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide (24683-25-8) → meloxicam (71125-38-7)

Conditions	Yield
With toluene-4-sulfonic acid; 1,2-dichloro-ethane	48%

methyl 3-oxo-2,3-dihydrobenzo[d][1,2]thiazol-2-acetate 1,1-dioxide (6639-62-9) → meloxicam (71125-38-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 25percent MeONa/MeOH / toluene / 4 h / 80 °C 2: 1M aq.NaOH / ethanol / 24 h / Ambient temperature 3: xylene / 48 h / Heating View Scheme

methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (35511-14-9) → meloxicam (71125-38-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1M aq.NaOH / ethanol / 24 h / Ambient temperature 2: xylene / 48 h / Heating View Scheme

saccharin (81-07-2) → meloxicam (71125-38-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) NaH / 1.) DMF, 50 deg C, 30 min, 2.) DMF, 4 h 2: 25percent MeONa/MeOH / toluene / 4 h / 80 °C 3: 1M aq.NaOH / ethanol / 24 h / Ambient temperature 4: xylene / 48 h / Heating View Scheme

5-methyl-2-thiazol-2-amine (7305-71-7) + ethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (24683-26-9) → 4-hydroxy-2-methyl-N-ethyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide + meloxicam (71125-38-7)

Conditions	Yield
In xylene at 139 - 140℃; for 32 - 37h;

Reaxys ID: 11649320 → meloxicam (71125-38-7)

Conditions	Yield
Stage #1: With sodium methylate In methanol for 0.166667h; Stage #2: With pyrographite In methanol Stage #3: With hydrogenchloride In methanol; water pH=1.12 - 3.70; Purification / work up;

Reaxys ID: 11649324 → meloxicam (71125-38-7)

Conditions	Yield
Stage #1: With sodium methylate In methanol for 0.166667h; Stage #2: With pyrographite In methanol Stage #3: With hydrogenchloride In methanol; water pH=2.3 - 2.4; Purification / work up;

5-methyl-2-thiazol-2-amine (7305-71-7) + methyl 2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (35511-15-0) → methanol (67-56-1) + 4-hydroxy-2-methyl-N-methyl-(5-methyl-2-thiazolyl)-2H-l,2-benzothiazine-3-carboxamide-1,1-dioxide + meloxicam (71125-38-7)

Conditions	Yield
pyrographite In xylene at 170 - 180℃; for 24h; Product distribution / selectivity;

5-methyl-2-thiazol-2-amine (7305-71-7) + ethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (24683-26-9) → methanol (67-56-1) + 4-hydroxy-2-methyl-N-methyl-(5-methyl-2-thiazolyl)-2H-l,2-benzothiazine-3-carboxamide-1,1-dioxide + meloxicam (71125-38-7)

Conditions	Yield
pyrographite In xylene at 170 - 180℃; for 24h; Product distribution / selectivity;

5-methyl-2-thiazol-2-amine (7305-71-7) + methyl 2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (35511-15-0) → N-[3,5-dimethyl-1,3-thiazol-2(3H)-ylidene]-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (1145656-36-5) + meloxicam (71125-38-7)

Conditions	Yield
With methane In 5,5-dimethyl-1,3-cyclohexadiene at 138 - 142℃; for 24h; Inert atmosphere; Large scale reaction;

ethene (74-85-1) → meloxicam (71125-38-7)

Conditions	Yield
In 5,5-dimethyl-1,3-cyclohexadiene; [(2)H6]acetone

(S)-Malic acid (97-67-6) + meloxicam (71125-38-7) → meloxicam:L-malic acid

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;

1,5-pentanedioic acid (110-94-1) + meloxicam (71125-38-7) → meloxicam glutaric acid (1246227-11-1)

Conditions	Yield
In chloroform for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;

meloxicam (71125-38-7) + maleic acid (110-16-7) → 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide maleic acid (1:1) (1174325-93-9)

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;
In ethyl acetate for 19h; Solvent;
In tetrahydrofuran at 20℃; for 24h;

meloxicam (71125-38-7) + benzoic acid (65-85-0) → meloxicam benzoic acid (1174325-83-7)

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;
Stage #1: meloxicam; benzoic acid for 0.25h; Milling; Stage #2: In acetone
In tetrahydrofuran at 20℃; for 0.5h; Solvent; Milling;

glycolic Acid (79-14-1) + meloxicam (71125-38-7) → meloxicam glycolic acid (1174325-97-3)

Conditions	Yield
In chloroform for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;

malonic acid (141-82-2) + meloxicam (71125-38-7) → meloxicam malonic acid (1174325-96-2)

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;

succinic acid (110-15-6) + meloxicam (71125-38-7) → 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide succinic acid (2:1)

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;
Stage #1: succinic acid; meloxicam for 0.25h; Milling; Stage #2: In acetone Solvent;
In ethyl acetate at 30℃; Solvent;

Adipic acid (124-04-9) + meloxicam (71125-38-7) → meloxicam:adipic acid

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;
Stage #1: Adipic acid; meloxicam for 0.25h; Milling; Stage #2: In acetone Solvent;

2,5-dihydroxybenzoic acid. (490-79-9) + meloxicam (71125-38-7) → meloxicam gentisic acid (1174325-98-4)

Conditions	Yield
for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;

meloxicam (71125-38-7) + 4-hydroxy-benzoic acid (99-96-7) → meloxicam 4-hydroxybenzoic acid (1174325-95-1)

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran

malic acid (617-48-1) + meloxicam (71125-38-7) → meloxicam:DL-malic acid

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;

meloxicam (71125-38-7) + salicylic acid (69-72-7) → 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide salicylic acid (1:1) (1174325-91-7)

Conditions	Yield
In ethyl acetate for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;
Stage #1: meloxicam; salicylic acid for 0.25h; Milling; Stage #2: In acetone

meloxicam (71125-38-7) + 3-Phenylpropionic acid (501-52-0) → meloxicam hydrocinnamic acid (1174326-03-4)

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran

meloxicam (71125-38-7) + 1-hydroxy-2-naphthoic acid (86-48-6) → 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide 1-hydroxy-2-naphthoic acid (1:1) (1174325-92-8)

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%
In tetrahydrofuran Product distribution / selectivity;
In dimethylsulfoxide-d6; water at 25 - 90℃; Solvent;	71 g

D-(+)-camphoric acid (124-83-4) + meloxicam (71125-38-7) → meloxicam (+)-camphoric acid (1246227-13-3)

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%

meloxicam (71125-38-7) + (2E)-but-2-enedioic acid (110-17-8) → C4H4O4*2C14H13N3O4S2

Conditions	Yield
In tetrahydrofuran for 0.5h;	100%

1-deoxy-1-(methylamino)-D-glucitol (6284-40-8) + meloxicam (71125-38-7) → N-methylglucamine salt of meloxicam (244241-52-9)

Conditions	Yield
In ethanol at 60℃; for 0.5h;	93%

meloxicam (71125-38-7) → 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, acetic acid solvate

Conditions	Yield
With acetic acid	92%

D-(+)-camphoric acid (124-83-4) + meloxicam (71125-38-7) → meloxicam:(+)-camphoric acid

Conditions	Yield
In chloroform at 20℃;	91%
In tetrahydrofuran Product distribution / selectivity;

methyl 2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (35511-15-0) + meloxicam (71125-38-7) → 5-methyl-2-thiazol-2-amine (7305-71-7)

Conditions	Yield
With montmorillonite MK10 impregnated with ZnCl2 In o-xylene for 24h; Reagent/catalyst; Reflux; Green chemistry;	90%

iron(II) acetate tetrahydrate + meloxicam (71125-38-7) → [bis(4-oxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide)iron(II)] tetrahydrate

Conditions	Yield
In methanol N2, mixed a hot solns., refluxed for 0.5 h; ppt. filtered, washed (hot methanol under N2), dried (vac., room temp.);elem. anal.;	88%

[osmium(II)dichloride(η6-p-cymene)]2 + meloxicam (71125-38-7) → dichlorido(4-hydroxy-2-methyl-1,1-dioxo-1,2-dihydro-λ'6-benzo[e][1,2]thiazine-3-carboxylic acid(5-methyl-thiazol-2-yl)amide)(η6-p-cymene)osmium(II)

Conditions	Yield
In dichloromethane at 20℃; for 12h; Inert atmosphere;	81%

ethanol (64-17-5) + zinc(II) acetate dihydrate (5970-45-6) + meloxicam (71125-38-7) → trans-[Zn(Hmel)2(EtOH)2]

Conditions	Yield
for 2h; Reflux;	80%

[ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 (52462-29-0) + meloxicam (71125-38-7) → dichlorido(4-hydroxy-2-methyl-1,1-dioxo-1,2-dihydro-λ'6-benzo[e][1,2]thiazine-3-carboxylic acid(5-methyl-thiazol-2-yl)amide)(η6-p-cymene)ruthenium(II)

Conditions	Yield
In dichloromethane at 20℃; for 12h; Inert atmosphere;	80%

copper(II) choride dihydrate + meloxicam (71125-38-7) → [Cu(meloxicam)2]

Conditions	Yield
In ethanol for 24h; Reflux;	79%

di-μ-bromo-bis[bromo(η(6)-para-cymene)ruthenium(II)] (90591-13-2) + meloxicam (71125-38-7) → bromido(4-hydroxy-2-methyl-1,1-dioxo-1,2-dihydro-λ'6-benzo[e][1,2]thiazine-3-carboxylic acid(5-methyl-thiazol-2-yl)amide)(η6-p-cymene)ruthenium(II)

Conditions	Yield
Stage #1: meloxicam With sodium methylate In methanol at 20℃; for 0.5h; Stage #2: di-μ-bromo-bis[bromo(η(6)-para-cymene)ruthenium(II)] In methanol at 20℃; for 4h;	79%

Upstream product

• 81-07-2 saccharin 
• 6639-62-9 methyl 3-oxo-2,3-dihydrobenzo[d][1,2]thiazol-2-acetate 1,1-dioxide 
• 35511-14-9 methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide 
• 7305-71-7 5-methyl-2-thiazol-2-amine 
• 35511-15-0 methyl 2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide 
• 74-85-1 ethene 
• 244241-52-9 N-methylglucamine salt of meloxicam 
• 24683-25-8 4-hydroxy-2-methyl-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide 
• 24683-26-9 ethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide 
• 95-50-1 1,2-dichloro-benzene 
• 892395-40-3 meloxicam potassium salt monohydrate 

Downstream Products

• 1145656-36-5 N-[3,5-dimethyl-1,3-thiazol-2(3H)-ylidene]-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide 
• 7305-71-7 5-methyl-2-thiazol-2-amine 
• 130262-93-0 5'-carboxy meloxicam 
• 1174326-03-4 meloxicam hydrocinnamic acid 
• 1174325-88-2 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide acetylsalicylic acid (1:1) 
• 1174325-91-7 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide salicylic acid (1:1) 
• 1174325-95-1 meloxicam 4-hydroxybenzoic acid 
• 1174325-98-4 meloxicam gentisic acid 
• 1174325-83-7 meloxicam benzoic acid 

Relevant articles and documents

Manufacture of high-purity meloxicam via its novel potassium salt monohydrate

An improved procedure for the manufacture of 4-hydroxy-2- methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (meloxicam) is described. The key intermediate of this protocol is the new potassium salt monohydrate of meloxicam, which makes possible the efficient removal of impurities, resulting in an environmentally friendly manufacturing process of the high-purity (>99.90%) drug substance.

USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS MELOXICAM AND PIROXICAM, ADMINISTERED INTRAVAGINALLY, FOR INTERRUPTION OF A WOMAN'S OVULATION PROCESS

The invention relates to the use of the non-steroidal anti-inflammatory compounds meloxicam and piroxicam to inhibit ovulation in women, the medication being administered by topically vaginal delivery.

Process for the Purification of Meloxicam

A process for purifying meloxicam form I from a crude meloxicam, which comprises: i. contacting the crude meloxicam with an amine in a non-aqueous solvent to form a meloxicam salt;ii. isolating the meloxicam salt;iii. dissolving the meloxicam salt in an aqueous solvent to form a salt solution; andiv. adding an acid to the salt solution to precipitate free meloxicam.

PROCESS FOR PREPARATION OF HIGH-PURITY MELOXICAM AND MELOXICAM POTASSIUM SALT

The invention provides a process for the preparation of high purity meloxicam of the Formula (II). The meloxicam raw product is reacted with the solution of potassium hydroxide or potassium carbonate, whereby high purity meloxicam potassium sait monohydrate is produced. Said sait is subsequently treated with minerai or organic acid to yield high-purity meloxicam.

Process for the purification of meloxicam

Process for the purification of meloxicam and in particular of the impurity composed of 4-hydroxy-2-methyl-N-ethyl-N'-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide comprising the following steps: a) the meloxicam is treated in crude form with an alcohol solution of an alkaline alcoholate at a temperature between 25 and 35°C.b) the solution obtained in step (a) is acidified to a pH between 1.5 and 4.0 and the precipitated product composed of meloxicam is filtered, the wet filtered product obtained from the previous step is crushed in a polar aprotic solvent and the product of the crushing is isolated by means of filtration and drying.

Process for the purification of meloxicam

The present invention relates to a process for the purification of meloxicam and in particular of the impurity composed of 4-hydroxy-2-methyl-N-ethyl-N′-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide and to meloxicam containing a quantity of less than 0.05% of the above-mentioned impurity (“ethylamide”).

Process for the preparation of crystalline form-1 of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide

The present invention is related to an improved process for preparing crystalline Form I of meloxicam, which produces the Form I in high yield.

Method for the treatment and prevention of cachexia

Cachexia, including anorexia and other forms of weight loss, is a frequent complication of acute and chronic infections, and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. The present invention includes methods for the treatment or prevention of cachexic conditions while maintaining the production of factors essential for infection control through the administration of an effective amount of a cyclooxygenase-2 selective inhibiting compound.

Effect of structural modification of enol-carboxamide-type nonsteroidal antiinflammatory drugs on COX-2/COX-1 selectivity

Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3- carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothiazines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4- dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.

4-HYDROXY-2H-1,2-BENZOTHIAZINE-3-CARBOXAMIDE-1,1,-DIOXIDES AND SALTS THEREOF

Compounds of the formula wherein R1 is hydrogen, methyl or ethyl; R2 is methyl, ethyl or n-propyl; and Y is hydrogen, methyl, methoxy, fluorine or chlorine; and non-toxic, pharmacologically acceptable salts thereof formed with an inorganic or organic base. The compounds as well as their salts are useful as antiphlogistics.