34552-84-6

Basic information

• Product Name: ISOXICAM
• Synonyms: )-,1,1-dioxide;2h-1,2-benzothiazine-3-carboxamide,4-hydroxy-2-methyl-n-(5-methyl-3-isoxazolyl;pacyl(antiinflammatory);ISOXICAM;4-Hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide;Pacyl;Vectren;W 8495
• CAS NO: 34552-84-6
• Molecular Formula: C₁₄H₁₃N₃O₅S
• Molecular Weight: 335.34
• EINECS: 252-084-5
• Product Categories: OCTOPIROX
• Mol File: 34552-84-6.mol
• Article Data: 9

Chemical Properties

• Melting Point: 265-271℃
• Boiling Point: 518.8°Cat760mmHg
• Flash Point: 267.5°C
• Appearance: /
• Density: 1.588
• Refractive Index: 1.686
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly, Heated), DMSO (Slightly), Methanol (Slightly, Heated, Soni
• PKA: 4.50±1.00(Predicted)
• CAS DataBase Reference: ISOXICAM(CAS DataBase Reference)
• NIST Chemistry Reference: ISOXICAM(34552-84-6)
• EPA Substance Registry System: ISOXICAM(34552-84-6)

Safety Data

• WGK Germany: 2
• RTECS: DL0703000
• Hazardous Substances Data: 34552-84-6(Hazardous Substances Data)

Usage

Description

Isoxicam is a non-steroidal antiinflammatory agent useful in the treatment of various forms of rheumatoid arthritis, osteoarthritis and musculoskeletal disorders. It is about one-tenth as potent as its structural relative sudoxicam; its similar long T1/2 (>30 hrs.) allows once-daily dosing.

Originator

Warner-Lambert (USA)

Uses

Different sources of media describe the Uses of 34552-84-6 differently. You can refer to the following data:
1. antiseborrheic
2. Isoxicam is used for the same indications as piroxicam. Synonyms for isoxicam are floxicam and maxicam.
3. Isoxicam is a potent, orally active, nonsteroidal anti-inflammatory drug.

Definition

ChEBI: A monocarboxylic acid amide that is piroxicam in which the pyrid-2-yl group is replaced by a 5-methyl-1,2-oxazol-3-yl group. A non-steroidal anti-inflammatory drug, it was withdrawn from the market in the 1980s following its association with cases of Steve s-Johnson syndrome.

Manufacturing Process

A mixture of 40.5 g (0.15 mol) of 3-carbethoxy-4-hydroxy-2-methyl-2H-1,2- benzothiazine 1,1-dioxide, 20.6 g (0.21 mol) of 3-amino-5-methylisoxazole, and 2,500 ml of xylene was refluxed for 24 hours in a Soxhlet apparatus, the thimble of which contained 60 g of Linde type 4A molecular sieve. The mixture was cooled to 25°C and the resulting crystalline precipitate was collected and washed with ether to give 44 g of crude product. Recrystallization from 1,600 ml of 1,4-dioxan gave 34.7 g of material, MP 265°C to 271°C dec.

Brand name

Maxicam (Parke-Davis);Floxicam;PACYL.

Therapeutic Function

Antiinflammatory

World Health Organization (WHO)

Isoxicam, a nonsteroidal anti-inflammatory agent, was introduced in 1983 for the treatment of rheumatic disorders. By 1985 its use had been associated with serious adverse effects, including four deaths from rare skin reactions. This led to its withdrawal in France followed immediately by the voluntary suspension of marketing worldwide by the major manufacturer.

Synthesis

Isoxicam, 1,1-dioxide 4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-1,2- benzothiazine-3-carboxamide (3.2.80), is synthesized analogous to piroxicam, using amidation of 1,1-dioxide 3-methoxycarbonyl-3,4-dihydro-2-H-1,2-benzothiazine-4-one (3.2.78) in the last stage with 3-amino-5-methylisoxazole, instead of 2-aminopyridine [127–130].

InChI:InChI=1/C14H13N3O5S/c1-8-7-11(16-22-8)15-14(19)12-13(18)9-5-3-4-6-10(9)23(20,21)17(12)2/h3-7,18H,1-2H3,(H,15,16,19)

Upstream product

• 59826-56-1 1-{[5-(4-Hydroxy-2-methyl-2H-1,2-benzothiazin-3-yl)-1,2,4-oxadiazol-3-yl]methyl}ethanone S,S,-dioxide 
• 80201-72-5 (1,1,3-Trioxo-1,3-dihydro-1λ⁶-benzo[d]isothiazol-2-yl)-acetic acid 2-methoxy-ethyl ester 
• 107124-72-1 Bis(2-methoxyethyl) 2-(N-carboxymethylsulfamoyl)benzoate 
• 80201-73-6 2-methoxyethyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide 
• 61680-15-7 methyl 2-<<<2-<(5-methyl-3-isoxazolyl)amino>-2-oxoethyl>amino>sulfonyl>benzoate 
• 5510-10-1 2-methyl-2H-1,2-benzothiazine-4-(3H)-one-1,1-dioxyde 
• 24683-21-4 4-hydroxy-2H-1,2-benzothiazine-3-carboxylic acid ethyl ester 1,1-dioxide 
• 40713-75-5 2-methyl-4-(1-pyrrolidinyl)-2H-1,2-benzothiazine 1,1-dioxide 
• 55387-64-9 2-Methyl-1,1-dioxo-4-pyrrolidin-1-yl-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carbonyl chloride 
• 128-44-9 saccharin sodium salt 
• 59826-55-0 1-{[5-(4-hydroxy-2H-1,2-benzothiazin-3-yl)-1,2,4-oxadiazol-3-yl]methyl}ethanone S,S-dioxide 
• 59826-54-9 N-(5-methyl-3-isoxazolyl)-3-oxo-1,2-benzisothiazole-2(3H)-acetamide 1,1-dioxide 
• 59826-53-8 α-chloro-N-(5-methylisoxazol-3-yl)acetamide 
• 38938-73-7 4-Hydroxy-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid (5-methyl-isoxazol-3-yl)-amide 

Relevant articles and documents

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.

Pharmaceutical preparation for the therapeutic treatment of rheumatic diseases

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 4-hydroxy-3-(heterocyclocarbamoyl)-2H-1,2-benzothiazine-1,1-dioxides

The present invention provides a process for the preparation of 4-hydroxy-3-(heterocyclocarbamoyl)-2H-1,2-benzothiazine-1,1-dioxides of the general formula: STR1 wherein R1 is a hydrogen atom or a methyl radical, R2 is a nitrogen-containing heterocyclic radical and R3 is a hydrogen or halogen atom or a methyl radical, and of the alkali metal, alkaline earth metal and amine salts thereof, by the reaction of an amine-substituted, nitrogen-containing heterocyclic compound with a halo-acetyl halide, reaction of the intermediate thus obtained with sodium benzoic acid sulphimide, ring expansion of the benzoisothiazole ring to give a benzothiazine ring and, in case R2 is to be an isoxazolyl radical, reverse rearrangement of the oxadiazole-ring formed by ring expansion to the isoxazolyl ring, wherein (in a one-pot reaction A) the reaction of an amine-substituted, nitrogen-containing heterocyclic compound with a halo-acetyl halide is carried out, without the addition of a base, in boiling ethyl acetate, the intermediate formed is, without isolation, reacted with sodium benzoic acid sulphimide and the reaction product isolated, whereafter, in a one-pot reaction B, the reaction product from the one-pot reaction A is reacted in a dipolar aprotonic solvent under an atmosphere of a protection gas with a strongly basic alkali-alkohole and thereafter with so much acid that about 2 equivalents of base remained unneutralized in the reaction solution and, if desired, the benzothiazine ring is N-methylated in the usual manner and the product obtained is, if desired, converted in known manner into an alkali metal, alkaline earth metal or amine salt.