15307-79-6 Usage
Chemical Description
Diclofenac sodium is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation.
Description
Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID) and a COX inhibitor, derived from benzeneacetic acid. It exhibits analgesic, antipyretic, and anti-inflammatory activities. As a sodium salt form of diclofenac, it is a non-selective reversible and competitive inhibitor of cyclooxygenase (COX), blocking the conversion of arachidonic acid into prostaglandin precursors. This leads to an inhibition of the formation of prostaglandins that are involved in pain, inflammation, and fever. Diclofenac sodium is an off-white crystalline solid and has various brand names, such as Solaraze, Voltaren, and Flectoran.
Uses
1. Used in Pharmaceutical Industry:
Diclofenac sodium is used as a pharmaceutical secondary standard for quality control, providing a convenient and cost-effective alternative to the preparation of in-house working standards.
2. Used in Pain Management:
Diclofenac sodium is used as an analgesic for the treatment of acute pain and inflammation, effective in various acute forms of pain.
3. Used in Inflammation Treatment:
Diclofenac sodium is used as an anti-inflammatory agent, treating conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.
4. Used in Antipyretic Applications:
Diclofenac sodium is used to reduce fever by inhibiting the formation of prostaglandins involved in fever regulation.
5. Used in Transdermal Drug Delivery:
Diclofenac sodium is used in transdermal administration, inhibiting carrageenan-induced paw edema in rats, and providing a non-invasive method for pain relief.
6. Used in Stabilizing Transthyretin:
Diclofenac sodium is used to stabilize the native tetrameric conformation of transthyretin (TTR) fibrils, preventing the formation of insoluble amyloidogenic TTR deposits.
7. Used in Inhibiting Cyclooxygenase (COX):
Diclofenac sodium is used as an inhibitor of COX-1 and COX-2, suppressing prostaglandin E2 synthesis and producing anti-inflammatory and analgesic effects.
8. Used in Parenteral Formulation:
Due to its poor solubility, diclofenac sodium is used in parenteral formulations containing solvents like propylene glycol and benzyl alcohol, allowing for intramuscular and intravenous administration.
Mechanisms of action
Putative mechanisms of action of diclofenac may include inhibition of leukotriene synthesis, inhibition of phospholipase A2, modulation of free arachidonic acid levels, stimulation of adenosine triphosphate-sensitive potassium channels via the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway and centrally mediated and neuropathic mechanisms. Other emerging mechanisms of action may include inhibition of peroxisome proliferator activated receptor-c, reduction in plasma and synovial substance P and interleukin-6 levels, inhibition of the thromboxane-prostanoid receptor and inhibition of acid-sensing ion channels.
Clinical Application
Clinical trials have demonstrated the analgesic efficacy of diclofenac sodium in terms of relieving moderate to severe postoperative pain in patients undergoing dental surgery or minor orthopaedic surgery. Subcutaneous diclofenac sodium also effectively relieved moderate to severe neuropathic pain, related to cancer or not. Diclofenac sodium was generally well tolerated in clinical trials, with injection-site reactions among the most commonly reported adverse events.
Originator
Voltaren,Fujisawa,Japan,1974
Manufacturing Process
Four grams of N-chloroacetyl-N-phenyl-2,6-dichloroaniline and 4 grams of
aluminum chloride are well mixed together and heated for 2 hours at 160°C.
The melt is cooled and poured onto about 50 grams of ice while it is still
warm. The oil which separates is dissolved in 50 ml of chloroform, the
chloroform solution is washed with 10 ml of water, dried over sodium sulfate
and concentrated under 11 torr. The residue is distilled. The 1-(2,6-
dichlorophenyl)-2-indolinone melts at 126°-127°C.A solution of 186 grams of 1-(2,6-dichlorophenyl)-2-indolinone in 660 ml of
ethanol and 660 ml of 2 N sodium hydroxide solution is refluxed for 4 hours.
The solution is then cooled and left to stand for 4 hours at 0°-5°C. The
crystals which form are filtered off and recrystallized from water. The sodium
salt of 2-(2,6-dichloroanilino)-phenylacetic acid melts at 283°-285°C. The
yield is 97% of theoretical, according to US Patent 3,558,690.
Therapeutic Function
Antiinflammatory
World Health Organization (WHO)
The World Health Organization currently has no information to
suggest that diclofenac is less safe than other widely available non-steroidal
antiinflammatory substances of this type, or that children are particularly liable to
react adversely. It is registered in many countries in several dosage forms,
including a 12.5 mg suppository indicated for juvenile arthritis.
Biochem/physiol Actions
Standard NSAID and cyclooxygenase (COX) inhibitor. Major metabolites are 4′-hydroxydiclofenac and 5′-hydroxydiclofenac. Has been used as substrate selective for CYP2C9.
Clinical Use
Diclofenac sodium is indicated for the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.
Veterinary Drugs and Treatments
The equine topical cream (Surpass?) is labeled for the control of
pain and inflammation associated with osteoarthritis in tarsal, carpal,
metacarpophalangeal, metarsophalangeal, and proximal interphalangeal
(hock, knee, fetlock, pastern) joints for use up to 10 days
duration. While, theoretically, diclofenac could be used systemically
(orally) in other veterinary species, there are approved and safer
alternatives.
Drug interactions
Potentially hazardous interactions with other drugs
antagonism of hypotensive effect; increased risk of
nephrotoxicity and hyperkalaemia.Analgesics: avoid concomitant use of 2 or more
NSAIDs, including aspirin (increased side effects);
avoid with ketorolac (increased risk of side effects
and haemorrhage).Antibacterials: possibly increased risk of convulsions
with quinolones; concentration reduced by
rifampicin.Anticoagulants: effects of coumarins and
phenindione enhanced; possibly increased risk of
bleeding with heparins, dabigatran and edoxaban -
avoid long term use with edoxaban; increased risk of
haemorrhage with IV diclofenac - avoid.Antidepressants: increased risk of bleeding with
SSRIs and venlaflaxine.Antidiabetic agents: effects of sulphonylureas
enhanced.Antiepileptics: possibly increased phenytoin
concentration.Ciclosporin: may potentiate nephrotoxicity;
concentration increased by ciclosporin.Cytotoxics: reduced excretion of methotrexate;
increased risk of bleeding with erlotinib.
Metabolism
Diclofenac undergoes first-pass metabolism and is It is then excreted in the form of glucuronide and sulfate
conjugates, mainly in the urine (about 60%) but also in
the bile (about 35%).
then extensively metabolised to 4′-hydroxydiclofenac,
5-hydroxydiclofenac, 3′-hydroxydiclofenac, and
4′,5-dihydroxydiclofenac by glucuronidation of the intact
molecule or more commonly by single and multiple
hydroxylation followed by glucuronidation.
Check Digit Verification of cas no
The CAS Registry Mumber 15307-79-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,5,3,0 and 7 respectively; the second part has 2 digits, 7 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 15307-79:
(7*1)+(6*5)+(5*3)+(4*0)+(3*7)+(2*7)+(1*9)=96
96 % 10 = 6
So 15307-79-6 is a valid CAS Registry Number.
InChI:InChI=1/C12H9Cl2N.C2H4O2.Na/c13-10-7-4-8-11(14)12(10)15-9-5-2-1-3-6-9;1-2(3)4;/h1-8,15H;1H3,(H,3,4);/q;;+1/p-1
15307-79-6Relevant articles and documents
Synthesis method of diclofenac sodium
-
, (2021/09/21)
The invention discloses a synthesis method of diclofenac sodium, which comprises the following steps: (1) toluene. An oil layer is obtained by adding 2, 6 -dichlorophenol and sodium carbonate, keeping warm and refluxing, extracting the oil layer with water, and adding an alkali heat-preserving reaction in the oil layer to obtain 2, 6 -dichloroaniline. (2) 1, 2 Dichlorodimethylaniline prepared in step (6 -) is heated and melted, chloroacetyl chloride is added dropwise, and the heat is subjected to heat preservation reaction after being heated to crystallize to obtain N - (2, 6 - dichlorophenyl) - phenyl - chloroacetamide. (3) 2 (N - 2 Dichlorophenyl) 6 - phenyl - chloroacetamide prepared in step (-) is reacted with the aluminum trichloride to give a solid 1 - (2, 6 -dichlorophenyl) -2 -indolinone. (4) 3 (1 - 2-dichlorophenyl) 6 -indolinone prepared in step (-2 -) is added to alkali liquor, stirred and heated to reflux to obtain diclofenac sodium. The synthesis method is stable, easy to operate, low in cost, high in yield and suitable for industrial production.
Preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate
-
, (2020/05/30)
The invention belongs to the field of chemical pharmacy, and relates to a production process of a chemical bulk drug, in particular to a preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate. The preparation method comprises the following steps: taking 2, 6-dichlorodiphenylamine and chloroacetyl chloride as initial raw materials; and completing acylation reaction, Lewis acidicionic liquid catalyzed Friedel-Crafts alkylation reaction and hydrolysis reaction by a one-pot method to finally obtain the 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate. The 2-[(2,6-dichlorophenyl) amino] sodium phenylacetate is synthesized by adopting a one-pot preparation scheme, has the advantages of short reaction time, simplicity in operation, mild conditions, high yield, good catalytic effect, high selectivity, recyclability and the like, and is beneficial to industrial production.
A General, Activator-Free Palladium-Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid
Wang, Lin,Neumann, Helfried,Beller, Matthias
supporting information, p. 6910 - 6914 (2018/06/04)
A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2-bis((tert-butyl(2-pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non-steroidal anti-inflammatory drugs (NSAIDs), under mild conditions in good yields.