27035-30-9

Usage

Uses

Used in Pharmaceutical Industry:
Oxametacin is used as an anti-inflammatory agent for reducing inflammation, pain, and fever. It works by inhibiting the cyclooxygenase (COX) enzymes, which are responsible for the production of prostaglandins that cause inflammation and pain.
Used in Orthopedic Applications:
In the orthopedic field, oxametacin is used as a pain reliever for patients undergoing surgeries or experiencing musculoskeletal disorders. Its analgesic properties help in managing postoperative pain and improving patient recovery.
Used in Veterinary Medicine:
Oxametacin is also utilized in veterinary medicine as an anti-inflammatory and analgesic agent for the treatment of various conditions in animals, such as arthritis, soft tissue injuries, and postoperative pain management.

Originator

Flogar, A.B.C. , Italy ,1976

Manufacturing Process

1 g of 1-p-chlorobenzoyl-2-methyl-5-methoxy-3-indoleacetic acid [J. Am. Chem. Soc. 85, 488-489 (1963)] is treated in a nitrogen stream with 10 ml thionyl chloride in which it promptly dissolves. The solution is quickly evaporated in vacuum and the residue (which typically is of a deep browngreen color) is distempered, twice or three times, with a few ml anhydrous benzene which is removed in vacuum each time. The resulting residue is thoroughly distempered with 5 ml anhydrous ether which dissolves most of the color impurities, and separated by filtering, purified by crystallizing from plenty of anhydrous ether, yielding a crystalline mass of needles of strawyellow color, melting point 124°C to 127°C. Yield: 0.700 g. Found: Cl % 18.62 (calculated 18.84). The product is relatively stable towards water and aqueous alkalies in which it proves to be insoluble even after dwelling therein several hours at room temperature. It reacts, better if at elevated temperature, with lower alcohols with which it forms the corresponding esters, and with ammonia under suitable conditions for forming the amide (melting point 219°C to 221°C). A solution of 1.330 g sodium hydroxide in 20 ml water is slowly admixed with 2.330 g hydroxylamine hydrochloride while cooling, whereupon 1 g chloride of 1-p-chlorobenzoyl-2-methyl-5-methoxy-3-indoleacetic acid is distempered in this neutral or slightly alkaline solution by vigorously stirring during a few minutes. The acid chloride reacts with the free hydroxylamine with considerable rapidity apparently without dissolving. The reaction is completed when a sample of the suspension shows to become clear on adding aqueous alkali. The crystalline pale-yellow mass of product is separated by filtering, lavishly washed with water and dried in vacuum. The crude product yield is actually quantitative. The product is purified with excellent yields by repeatedly crystallizing from hot dioxane and washing with ether: melting point 181°C to 182°C (dec.).

Therapeutic Function

Antiinflammatory

Safety Profile

Poison by ingestion and intraperitoneal routes. An anti-inflammatory agent. When heated to decomposition it emits toxic fumes of Clí and NOx.

InChI:InChI=1/C19H17ClN2O4/c1-11-15(10-18(23)21-25)16-9-14(26-2)7-8-17(16)22(11)19(24)12-3-5-13(20)6-4-12/h3-9,25H,10H2,1-2H3,(H,21,23)

Upstream product

• 1601-18-9 indomethacin methyl ester 
• 20357-37-3 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetyl chloride 
• 53-86-1 [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid 

Relevant academic research and scientific papers

P(III)-Assisted Electrochemical Access to Ureas via in situ Generation of Isocyanates from Hydroxamic Acids

An external oxidant-free protocol for the generation of isocyanates from hydroxamic acids assisted by trivalent phosphine under mild electrochemical conditions was reported. The process started with the anodic oxidation of hydroxamic acids, followed by reacting with phosphine to form corresponding alkoxyphosphoniums and subsequent rearrangement with the release of tri-substituted phosphine oxide as the driving force to give isocyanates, which were trapped by N-based nucleophiles to produce various ureas. This method provides a broadly applicable procedure to access isocyanate intermediates under mild electrochemical conditions.

Thioether-Directed NiH-Catalyzed Remote γ-C(sp3)-H Hydroamidation of Alkenes by 1,4,2-Dioxazol-5-ones

A NiH-catalyzed thioether-directed cyclometalation strategy is developed to enable remote methylene C-H bond amidation of unactivated alkenes. Due to the preference for five-membered nickelacycle formation, the chain-walking isomerization initiated by the NiH insertion to an alkene can be terminated at the γ-methylene site remote from the alkene moiety. By employing 2,9-dibutyl-1,10-phenanthroline as the ligand and dioxazolones as the reagent, the amidation occurs at the γ-C(sp3)-H bonds to afford the amide products in up to 90% yield (>40 examples) with remarkable regioselectivity (up to 24:1 rr).

Molecular simulation and activity studies of oxametacin as an HDAC inhibitor

Background: Oxametacin is a non-steroidal anti-inflammatory drug with pharmacophores of classic histone deacetylase inhibitors. To evaluate the histone deacetylase enzymatic inhibition and antitumor potential of Oxametacin, molecular docking, molecular dynamic simulation and in vitro activity assay processes were performed in the present study. Methods: In the docking study, multiple π - π stacking and H-bond interactions were discovered to play significant roles in the Oxametacin-HDAC3 bindings. Results: Such interactions were proved to be stable by the molecular dynamic simulation. Enzymatic inhibition assay showed potent inhibitory activity of Oxametacin (IC50 value of 0.18 μM) against Hela cell nucleus extract compared with SAHA (0.21 μM). Conclusion: In the isoform selectivity assay, Oxametacin exhibited selectivity for HDAC3 (0.13 μM) over HDAC6 (0.46 μM). In the antiproliferative test, Oxametacin exhibited leukemic cell lines selectivity against the solid tumor cell lines. Current studies reveal that Oxametacin can be used as a lead compound in further development of histone deacetylase inhibitors for the anticancer therapy.

2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-2-hydrogen-indole-3-yl)-N-hydroxyacetamide adopted as histone deacetylase inhibitor and preparation method and application thereof

The invention belongs to the technical field of medicinal chemistry, particularly relates to a histone deacetylase inhibitor and a preparation method and application thereof, provides an efficient histone deacetylase inhibitor, relates to a compound of the formula (I), further relates to a pharmaceutical acceptable salt, a solvate and a prodrug of the compound, and further relates to a pharmaceutical composition containing the compound of the formula (I) and pharmaceutical application of the pharmaceutical composition. The histone deacetylase inhibitor can effectively treat diseases caused by histone deacetylase abnormal activity expression.

Structure-based design, synthesis, and biological evaluation of indomethacin derivatives as cyclooxygenase-2 inhibiting nitric oxide donors

Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.

2-METHYL INDOLE CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE

The invention describes compositions and kits comprising 2-methyl indole cyclooxygenase 2 (COX-2) selective inhibitors or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The 2-methyl indole cyclooxygenase 2 selective inhibitors can be optionally substituted with at least one nitric oxide enhancing group. The invention also provides methods for (a) treating inflammation, pain and fever; (b) treating gastrointestinal disorders and/or improving the gastrointestinal properties of COX-2 selective inhibitors; (c) facilitating wound healing; (d) treating renal and/or respiratory toxicities; (e) treating disorders resulting from elevated levels of cyclooxygenase-2; (f) improving the cardiovascular profile of COX-2 selective inhibitors; (g) treating diseases resulting from oxidative stress; (h) treating endothelial dysfunctions; (j) treating diseases caused by endothelial dysfunctions; (k) treating inflammatory disease states and/or disorders; (1) treating ophthalmic disorders; and (m) treating peripheral vascular diseases. The nitric oxide enhancing groups are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.

METHOD FOR THE PROPHYLAXIS OR TREATMENT OF CARCINOMAS

There are described methods for the prophylaxis or treatment of carcinomas in a mammalian subject comprising administering a metal complex having anti-inflammatory activity to the mammal. Typically, the complex is a complex of at least one metal and at least one non-steroidal anti-inflammatory drug (NSAID). Suitable complexes include a complex of a metal and a carboxylate, or a derivative of a carboxylate, having anti-inflammatory activity.