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3-Oxo-1,2-benzisothiazole-2-acetic acid methyl ester 1,1-dioxide (2) 1000 ml three-necked flask was added DMF (410 ml), under magnetic stirring was added sodium saccharin (241 g, 1.0 mol, commercially available, containing water of crystallisation), basically dissolved, and then added methyl chloroacetate (162.8 g, 1.5 mol). The mixture was gradually heated to reflux (bath temperature 130-140°C) and reacted for 3 h. Cooled to room temperature, the reaction mixture was added to cold water (820 ml) under stirring, and a white solid was precipitated immediately. Filtered, washed with water (100ml×3). Vacuum drying (60°C) gave a white solid 2. 4-Hydroxy-2H-2H-2H-2H-2H-2H-2H-2H-2H-2H-2H-2H2).
.4-Hydroxy-2H-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxide (3) 250 ml three-necked flask was added with anhydrous methanol (60 ml), and then sodium metal (6.5 g, 0.28 mol) was added in batches until the sodium was completely dissolved (can be slightly heated), then stirred electrically and heated to a bath temperature of 110-120°C. Immediately, one-time rapid addition of powder 2 ( Immediately add powder 2 ( 18g, 0.07mol) quickly, while stirring vigorously (pay attention to prevent wash out), instant reaction to get orange-yellow slurry. Remove the oil bath, then add ice (72g)-concentrated hydrochloric acid (28ml) mixture, stirring, at the same time with an ice-water bath cooled to below 10 ° C, precipitation of white solid, filtration, washing, vacuum drying (60 ° C) to obtain a white solid 3.
4-Hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxide (4) 250 ml three-necked flask was charged with ethanol (72 ml), stirred magnetically, and then 3 (14.4 g, 56.47 mmol) was added, and then aqueous (72 ml) solution of sodium hydroxide (3.16 g) was added. The reaction was exothermic and after complete dissolution of the solid, the temperature was lowered to below 20°C, then dimethyl sulphate (11.81 g, 93.74 mmol) was added dropwise (keeping the internal temperature not exceeding 25°C). A large amount of solid precipitated after a few minutes and reacted at about 25°C for 15 h. Cooled to below 10°C, filtered and washed with 50% ethanol to give white solid 4.
Uses and functions of Levosulpiride.
Used for rheumatoid arthritis, rheumatoid arthritis, osteoarthritis, and painful soft tissue injuries
Non-steroidal anti-inflammatory drugs. Used for osteoarthritis, rheumatoid arthritis
Cyclooxygenase-2 inhibitor, used for rheumatoid arthritis, painful osteoarthritis symptoms treatment.
Pharmacological Effects of Meloxicam Raw.
1.Analgesic effect Like other non-steroidal anti-inflammatory drugs, meloxicam is mainly used for mild and moderate chronic dull pain, such as neuralgia, arthralgia, etc. It has a strong and long-lasting analgesic effect on experimental inflammatory pain in rats. It has a strong and long-lasting analgesic effect on inflammatory pain in experimental rats. In male Lewis rats suffering from experimental RA, the dose of 0.063-0.5mg-kg-1, once a day, orally administered for 21d, was not only effective on the redness and swelling of the hind paw and bone and cartilage damage, but also had a strong and long-lasting analgesic effect on the inflammatory pain, and the oral dose of up to 10mg-kg-1 had no effect on the central nervous system, which was similar to that of indomethacin, and the effect of meloxicam on visceral pain was similar to that of indomethacin. Meloxicam has no analgesic effect on visceral pain.
2.Antipyretic effect Meloxicam can reduce the body temperature of febrile patients, but it has almost no effect on the normal body temperature. For example, in the anti-inflammatory dose range, meloxicam has no effect on the normal body temperature of rats, but can reduce the yeast-induced fever. In rats with endotoxin-induced fever given intravenously, Meloxicam was injected 0.1, 0.3 or 0.5 mg-kg-1, twice a week, respectively, and found to have a significant hypothermic effect, with the optimal antipyretic dose being 0.3 mg-kg-1. twice a week.
3.Anti-inflammatory effect in animal inflammation models (mainly including carrageenan gum, white clay-induced murine hind paw oedema model implanted cotton wool murine granuloma model; carrageenan gum-induced pleurisy and liquid paraffin as an adjuvant to Mycobacterium tuberculosis-induced arthritis model), Meloxicam have shown strong anti-inflammatory activity. In keratine-induced pleurisy, unlike indomethacin, meloxicam reduced pleurisy secretion and inhibited leukocyte trafficking. In rat pleurisy, meloxicam inhibited prostaglandin E2 (PGE2) biosynthesis 2-fold as much as piroxicam and 8-fold as much as diclofenac.
Production method of Bulk Meloxicam Powder.
Refluxing of 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-amino-5-methylthiazole in xylene gave meloxicam in 74% yield.
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