53164-05-9 Usage
Description
Acemetacin, also known as a carboxylic ester, is the carboxymethyl ester of indometacin. It is a non-steroidal anti-inflammatory drug (NSAID) characterized by its light yellow solid appearance. Acemetacin is known for its potent inhibition of cyclooxygenase-2 (COX-2) enzyme, which contributes to its anti-inflammatory, analgesic, and anti-tumor properties.
Uses
Used in Pharmaceutical Industry:
Acemetacin is used as an analgesic and anti-inflammatory agent for the treatment of various conditions such as rheumatoid arthritis, osteoarthritis, and low back pain. It helps alleviate pain and reduce inflammation by inhibiting the COX-2 enzyme, which is responsible for the production of prostaglandins that cause inflammation and pain.
Used in Postoperative Care:
Acemetacin is used as a postoperative analgesic and anti-inflammatory drug to manage pain and inflammation following surgical procedures. Its effectiveness in reducing postoperative pain and inflammation contributes to faster recovery and improved patient outcomes.
Used in Oncology:
Acemetacin is used as an anti-tumor agent, particularly in the treatment of colon cancer. Its anti-tumor activity is attributed to its ability to inhibit the COX-2 enzyme, which plays a role in tumor growth and progression. Additionally, it may have potential synergistic effects when combined with other chemotherapeutic drugs, enhancing their efficacy and chemo-sensitivity in resistant cases.
Used in Drug Delivery Systems:
To improve the bioavailability and therapeutic outcomes of Acemetacin, various drug delivery systems have been developed. These systems, including organic and metallic nanoparticles, serve as carriers for Acemetacin, enhancing its delivery to target tissues and cells, and potentially reducing side effects associated with traditional administration methods.
Originator
Rantudil ,Bayer ,W. Germany ,1980
Manufacturing Process
25.4 g (0.050 mol) of [1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-
indoleacetoxy]-benzyl acetate were dissolved in 400 ml of glacial acetic acid
and hydrogenated on 2.0 g of palladium carbon at room temperature. After
the absorption of hydrogen had finished (1 hour), the catalyst was filtered off,
the filtrate was concentrated by evaporation under vacuum and the compound
was caused to crystallize by adding petroleum ether. The compound melted at
149.5-150.5°C (determined on the micro-Kofler bench); the yield was 19.4 g
which corresponds to 93% of the theoretical yield.
The starting material for the above step may be prepared as follows: 5 g
(0.016 mol) of N1-(p-methoxyphenyl)-p-chlorobenzhydrazide hydrochloride
and 4.75 g (0.018 mol) of benzyl levulinoyloxyacetate were heated in 25 ml of
glacial acetic acid for 3 hours at 80°C. The solvent was then evaporated off
under vacuum. The residue was taken up in chloroform and the solution was
washed neutral by shaking with sodium bicarbonate solution and thereafter
with water. After drying the chloroform solution, this was subjected to
chromatography on aluminium oxide, the eluate was concentrated by
evaporation and the viscous oil remaining as residue was crystallized by
adding ether. The compound melted at 94-95°C. The yield was 4.1 g which
corresponds to 50.7% of the theoretical yield.
Therapeutic Function
Antiinflammatory
Safety Profile
Poison by ingestion, subcutaneous,intraperitoneal, intravenous, and intramuscular routes. Anexperimental teratogen. Other experimental reproductiveeffects. When heated to decomposition it emits toxic fumesof Cl?? and NOx. An anti-inflammatory agent.
Check Digit Verification of cas no
The CAS Registry Mumber 53164-05-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,3,1,6 and 4 respectively; the second part has 2 digits, 0 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 53164-05:
(7*5)+(6*3)+(5*1)+(4*6)+(3*4)+(2*0)+(1*5)=99
99 % 10 = 9
So 53164-05-9 is a valid CAS Registry Number.
InChI:InChI=1/C21H18ClNO6/c1-12-16(10-20(26)29-11-19(24)25)17-9-15(28-2)7-8-18(17)23(12)21(27)13-3-5-14(22)6-4-13/h3-9H,10-11H2,1-2H3,(H,24,25)
53164-05-9Relevant articles and documents
Preparation method of acemetacin
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Paragraph 0002; 0011-0014, (2020/12/05)
The invention discloses a preparation method of acemetacin. The preparation method comprises the following steps: (1) introducing hydrogen chloride into glacial acetic acid to prepare an acetic acid solution of hydrogen chloride; (2) adding acetic anhydride into the acetic acid solution of hydrogen chloride prepared in the step (1); (3) adding acemetacin tert-butyl ester into the hydrogen chloride-acetic acid-acetic anhydride mixed acidolysis solution obtained in the step (2), and stirring at a constant temperature; (4) after the reaction is finished, cooling, carrying out standing crystallization, filtering, and carrying out top-washing to obtain a crude product acemetacin; and (5) refining the crude product acemetacin to obtain the finished product acemetacin. The invention provides a preparation method of acemetacin, wherein the influence of moisture in raw materials on an acidolysis reaction of acemetacin tert-butyl ester is eliminated on the premise of adopting the existing equipment, so that the product yield is increased, the production cost is lowered, and the economic benefit is improved.
Preparation method of acemetacin
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Paragraph 0023-0028; 0030-0035; 0037-0042; 0044-0049; 0051-0, (2018/09/12)
The invention discloses a synthesis method of acemetacin. The synthesis method includes the steps that A, acemetacin benzyl ester is prepared according to the patent US4600783; B, the acemetacin benzyl ester is dissolved in a solvent, wherein the solvent is one of acetonitrile, methylbenzene and dichloromethane, a benzyl kation scavenging agent is added, the scavenging agent is one of anisole, phenol and N,N-dimethylaniline, and a solution A is obtained; C, aluminum chloride is added into the solvent, the prepared solution A is added at zero temperature, and the materials are stirred at normaltemperature; D, after the reaction is completed, a reaction mixture is poured into ice water, the materials are stirred and then filtered, and crude acemetacin is obtained; E, the obtained crude acemetacin is recrystallized according to the volume ratio of acetone to water being 2:1, vacuum drying is carried out, and the pure acemetacin is obtained. The method is easy to carry out, easy and convenient to operate and suitable for large-scale preparation, the price of aluminum chloride is low, no dechlorinated byproducts are generated, the purity of the acemetacin can reach and be larger than 99.8% only through one step of simple recrystallization, and no heavy metal residues are generated.
Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats
Gynther, Mikko,Ropponen, Jarmo,Laine, Krista,Lepp?nen, Jukka,Haapakoski, Paula,Peura, Lauri,J?rvinen, Tomi,Rautio, Jarkko
supporting information; experimental part, p. 3348 - 3353 (2010/03/05)
The brain uptake of solutes is efficiently governed by the blood-brain barrier (BBB). The BBB expresses a number of carrier-mediated transport mechanisms, and new knowledge of these BBB transporters can be used in the rational targeted delivery of drug molecules for active transport. One attractive approach is to conjugate an endogenous transporter substrate to the active drug molecule to utilize the prodrug approach. In the present study, ketoprofen and indomethacin were conjugated with glucose and the brain uptake mechanism of the prodrugs was determined with the in situ rat brain perfusion technique. Two of the prodrugs were able to significantly inhibit the uptake of glucose transporter (GluT1)-mediated uptake of glucose, thereby demonstrating affinity to the transporter. Furthermore, the prodrugs were able to cross the BBB in a temperature-dependent manner, suggesting that the brain uptake of the prodrugs is carrier-mediated.