Welcome to LookChem.com Sign In|Join Free

CAS

  • or

38194-50-2

Post Buying Request

38194-50-2 Suppliers

Recommended suppliersmore

  • Product
  • FOB Price
  • Min.Order
  • Supply Ability
  • Supplier
  • Contact Supplier

38194-50-2 Usage

Used in Particular Diseases

Acute Gouty Arthritis: Dosage and Frequency:?200 mg twice daily for 7–10 days

Description

Many non-steroidal anti-inflammatory drugs (NSAIDs) are potent but non-selective inhibitors of both COX-1 and COX-2 in humans. Sulindac is one of the older NSAIDs, an isostere of indomethacin developed before the inducible form of COX-2 was discovered. Although a number of NSAIDs have been found to protect against digestive tract cancers, sulindac has an extensive epidemiology documenting reduced human colorectal cancer. In murine models, sulindac was found not only to inhibit the enzymatic activity of polyp-associated COX-2, but also to downregulate the expression of colonic COX-2 protein to control levels.

Chemical Properties

Yellow Crystalline Solid

Originator

Imbaral,Sharp and Dohme ,W. Germany,1976

Uses

Different sources of media describe the Uses of 38194-50-2 differently. You can refer to the following data:
1. Sulindac is used for relieving weak to moderate pain in rheumatoid arthritis and osteoarthritis.
2. A non-steroidal anti-inflammatory agent. An anti-inflammatory
3. Sulindac is a non-steroidal anti-inflammatory drug.

Definition

ChEBI: A monocarboxylic acid that is 1-benzylidene-1H-indene which is substituted at positions 2, 3, and 5 by methyl, carboxymethyl, and fluorine respectively, and in which the phenyl group of the benzylidene moiety is substituted at the ara position by a methylsulfinyl group. It is a prodrug for the corresponding sulfide, a non-steroidal anti-inflammatory drug, used particularly in the treatment of acute and chronic inflammatory conditions.

Indications

Sulindac (Clinoril) is chemically related to indomethacin and is generally used for the same indications. It is a prodrug that is metabolized to an active sulfide metabolite and an inactive metabolite. The most frequently reported side effects are GI pain, nausea, diarrhea, and constipation. The incidence of these effects is lower than for indomethacin, presumably because sulindac is a prodrug and thus the active metabolite is not highly concentrated at the gastric mucosa. As with indomethacin, a rather high incidence of CNS side effects (dizziness, headache) also occurs.

Manufacturing Process

The following process sequence is described in US Patent 3,654,349:p-Fluoro-α-Methylcinnamic Acid: 200 grams (1.61 mols) pfluorobenzaldehyde, 3.5 grams (2.42 mols) propionic anhydride and 155 grams (1.61 mols) sodium propionate are mixed in a 1 liter three-necked flask which had been flushed with nitrogen. The flask is heated gradually in an oilbath to 140°C. After 20 hours the flask is cooled to 100°C and the contents are poured into 8 liters of water. The precipitate is dissolved by adding 302 grams potassium hydroxide in 2 liters of water. The aqueous solution is extracted with ether, and the ether extracts washed with potassium hydroxide solution. The combined aqueous layers are filtered, acidified with concentrated HCl, filtered and the collected solid washed with water, thereby producing pfluoro- α-methylcinnamic acid which is used as obtained.p-Fluoro-α-Methylhydrocinnamic Acid: To 177.9 grams (0.987 mol) p-fluoro-α- methylcinnamic acid in 3.6 liters ethanol is added 11.0 grams of 5% Pd/C and the mixture reduced at room temperature under a hydrogen pressure of 40 psi. Uptake is 31/32 pounds (97% of theoretical). After filtering the catalyst, the filtrate is concentrated in vacuo to give the product p-fluoro-α- methylhydrocinnamic acid used without weighing in next step.6-Fluoro-2-Methylindanone: To 932 grams polyphosphoric acid at 70°C on the steam bath is added 93.2 grams (0.5 mol) p-fluoro-α-methylhydrocinnamic acid slowly with stirring. This temperature is gradually raised to 95°C and the mixture kept at this temperature for 1 hour. The mixture is allowed to cool and added to 2 liters of water. The aqueous layer is extracted with ether, the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water, and then dried. The ether filtrate is concentrated with 200 grams silica-gel, and added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5 to 10% etherpetroleum ether and followed by TLC to give 6-fluoro-2-methylindanone.5-Fluoro-2-Methylindene-3-Acetic Acid: A mixture of 18.4 grams (0.112 mol) of 6-fluoro2-methylindanone, 10.5 grams (0.123 mol) cyanacetic acid, 6.6 grams acetic acid and 1.7 grams ammonium acetate in 15.5 ml dry toluene is refluxed with stirring for 21 hours, as the liberated water is collected in a Dean Stark trap. The toluene is concentrated and the residue dissolved in 60 ml of hot ethanol and 14 ml of 2.2 N aqueous potassium hydroxide solution. 22 grams of 85% KOH in 150 ml of water is added and the mixture refluxed for 13 hours under N2. The ethanol is removed under vacuum, 500 ml water added, the aqueous solution washed well with ether and then boiled with charcoal. The aqueous filtrate is acidified to pH 2 with 50% hydrochloric acid, cooled and the precipitate collected in this way dried 5-fluoro-2-methylindenyl- 3-acetic acid (MP 164° to 166°C) is obtained.5-Fluoro-2-Methyl-1-(p-Methylthiobenzylidene)-3-Indenylacetic Acid: 15 grams (0.072 mol) 5-fluoro-2-methyl-3-indenylacetic acid, 14.0 grams (0.091 mol) p-methylthiobenzaldehyde and 13.0 grams (0.24 mol) sodium methoxide are heated in 200 ml methanol at 60°C under nitrogen with stirring for 6 hours. After cooling the reaction mixture is poured into 750 milliliters of ice-water, acidified with 2.5 N hydrochloric acid and the collected solid triturated with a little ether to produce 5-fluoro-2-methyl-1-(p-methylthiobenzylidene)-3- indenylacetic acid (MP 187° to 188.2°C).5-Fluoro-2-Methyl-1-(p-Methylsulfinylbenzylidene)-3-Indenylacetic Acid: To a solution of 3.4 grams (0.01 mol) 5-fluoro-2-methyl-1-(pmethylthiobenzylidene)- 3-indenylacetic acid in a 250 ml mixture of methanol and 100 ml acetone is added a solution of 3.8 grams (0.018 mol) of sodium periodate in 50 ml water with stirring.450 ml water is added after 18 hours and the organic solvents removed under vacuum below 30°C. The precipitated product is filtered, dried and recrystallized from ethyl acetate to give 5-fluoro-2-methyl-1-(pmethylsulfinylbenzylidene)- 3-indenylacetic acid. Upon repeated recrystallization from ethylacetate there is obtained cis-5-fluoro-2-methyl-1- (p-methylsulfinylbenzylidene)-3-indenylacetic acid (MP 184° to 186°C).

Brand name

Clinoril (Merck).

Therapeutic Function

Antiinflammatory

General Description

Sulindac, (Z)-5-fluoro-2-methyl-1-([p-(methylsulfinyl)phenyl]methylene)-1H-indene-3-acetic acid (Clinoril), isan NSAID prodrug that contains a chiral sulfoxide moietybut is marketed as the racemate because it undergoes invivo reduction by the hepatic enzymes into its achiral, activemetabolite, methyl sulfide that exhibits potent andnonselective COX inhibition similar to indomethacin.The parent sulfoxide has a plasma half-life of 8 hours, andthe active methyl sulfide metabolite is 16.4 hours. The morepolar and inactive sulfoxide is virtually the only form excretedinto the renal tubules, thus sulindac is believed to haveminimal nephrotoxicity associated with indomethacin. Thelong half-life of sulindac is caused by the extensive enterohepaticcirculation and reactivation of the inactive sulfoxideexcreted. Coadministration of aspirin is contraindicated becauseit considerably reduces the sulfide blood levels. Carefulmonitoring of patients with a history of ulcers is recommended.Gastric bleeding, nausea, diarrhea, dizziness, andother adverse effects have been noted with sulindac, but witha lower frequency than with aspirin. Sulindac is recommendedfor RA, OA, and ankylosing spondylitis.

Biological Activity

Prodrug. Metabolizes to sulindac sulfide, a cyclooxgenase inhibitor that represses ras signaling, and sulindac sulfone, an antitumor agent, following oral administration in vivo . Widely used anti-inflammatory agent.

Biochem/physiol Actions

Nonsteroidal anti-inflammatory; preferential inhibitor of COX-1.

Pharmacokinetics

Sulindac is well absorbed on oral administration (90%), reaches peak plasma levels within 2 to 4 hours, and being acidic (pKa = 4.5), is highly bound to serum proteins (93%). The metabolism of sulindac plays a major role in its actions, because all of the pharmacological activity is associated with its major metabolite. Sulindac is, in fact, a pro-drug, the sulfoxide function being reduced to the active sulfide metabolite. Sulindac is absorbed as the sulfoxide, which is not an inhibitor of prostaglandin biosynthesis in the GI tract. Prostaglandins exert a protective effect in the GI tract, and inhibition of their synthesis here leads to many of the GI side effects noted for most NSAIDs. Once sulindac enters the circulatory system, it is reduced to the sulfide, which is an inhibitor of prostaglandin biosynthesis in the joints. Thus, sulindac produces less GI side effects, such as bleeding, ulcerations, and so on, than indomethacin and many other NSAIDs. In addition, the active metabolite has a plasma half-life approximately twice that of the parent compound (~16 hours versus 8 hours), which favorably affects the dosing schedule. In addition to the sulfide metabolite, sulindac is oxidized to the corresponding sulfone, which is inactive. A minor product results from hydroxylation of the benzylidene function and the methyl group at the 2-position. Glucuronides of several metabolites also are found. Sulindac as well as the sulfide and the sulfone metabolites are all highly protein-bound. Despite the fact that the sulfide metabolite is a major activation product and is found in high concentration in human plasma, it is not found in human urine, perhaps because of its high degree of protein binding.

Clinical Use

Sulindac is indicated for long-term use in the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and acute gouty arthritis. The usual maximum dosage is 400 mg/day, with starting doses recommended at 150 mg twice a day. It is recommended that sulindac be administered with food.

Side effects

Whereas the toxicity of sulindac is lower than that observed for indomethacin and other NSAIDs, the spectrum of adverse reactions is very similar. The most frequent side effects reported are associated with irritation of the GI tract (e.g., nausea, dyspepsia, and diarrhea), although these effects generally are mild. Effects on the CNS (e.g., dizziness and headache) are less common. Dermatological effects are less frequently encountered.

Synthesis

Sulindac, 5-fluoro-2-methyl-1-[n-(methylsulfinyl)benzyliden]inden-3-acetic acid (3.2.67) is synthesized in a multi-step synthesis from n-fluorobenzaldehyde, which upon condensation with propionic acid anhydride in the presence of sodium acetate gives 4-fluoro-α- methylcinnamic acid (3.2.62). Reduction of the double bond by hydrogene using a palladium on carbon catalyst gives 4-fluoro-α-methyldihydrocinnamic acid (3.2.63). In the presence of polyphosphoric acid, the resulting product undergoes cyclization to 5-fluoro-2-methyl-3- indanone (3.2.64). The resulting ketone undergoes a Knoevenagel reaction with cyanoacetic acid and is further decarboxylated into 5-fluoro-2-methyliden-3-acetic acid (3.2.65). Condensation of the product with n-mercaptobenzaldehyde in the presence of sodium methoxide gives 5-fluoro- 2-methyl-1-(4-methylthiobenzyliden)-3-indenacetic acid (3.2.66), and the sulfur atom is oxidized by sodium periodate into the desired sulfoxide (3.2.67), sulindac [119–122].

Drug interactions

Potentially hazardous interactions with other drugs ACE inhibitors and angiotensin-II antagonists: 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. Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparins, dabigatran and edoxaban - avoid long term use with edoxaban. Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine. Antidiabetic agents: effects of sulphonylureas enhanced. Antiepileptics: possibly increased phenytoin concentration. Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir. Ciclosporin: may potentiate nephrotoxicity. Cytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinib. Dimethyl sulfoxide: avoid concomitant use. Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect; hyperkalaemia with potassium-sparing diuretics. Lithium: excretion decreased. Pentoxifylline: increased risk of bleeding. Tacrolimus: increased risk of nephrotoxicity.

Metabolism

Sulindac is metabolised by reversible reduction to the sulfide metabolite, which appears to be the active form, and by irreversible oxidation to the sulfone metabolite. About 50% is excreted in the urine mainly as the sulfone metabolite and its glucuronide conjugate, with smaller amounts of sulindac and its glucuronide conjugate; about 25% appears in the faeces, primarily as sulfone and sulfide metabolites. Sulindac and its metabolites are also excreted in bile and undergo extensive enterohepatic circulation.

Check Digit Verification of cas no

The CAS Registry Mumber 38194-50-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,8,1,9 and 4 respectively; the second part has 2 digits, 5 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 38194-50:
(7*3)+(6*8)+(5*1)+(4*9)+(3*4)+(2*5)+(1*0)=132
132 % 10 = 2
So 38194-50-2 is a valid CAS Registry Number.
InChI:InChI=1/C20H17FO3S/c1-12-17(9-13-3-6-15(7-4-13)25(2)24)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9+

38194-50-2 Well-known Company Product Price

  • Brand
  • (Code)Product description
  • CAS number
  • Packaging
  • Price
  • Detail
  • Sigma-Aldrich

  • (S2180000)  Sulindac  European Pharmacopoeia (EP) Reference Standard

  • 38194-50-2

  • S2180000

  • 1,880.19CNY

  • Detail
  • Sigma

  • (S8139)  Sulindac  ≥98.0%

  • 38194-50-2

  • S8139-5G

  • 792.09CNY

  • Detail
  • Sigma

  • (S8139)  Sulindac  ≥98.0%

  • 38194-50-2

  • S8139-25G

  • 3,168.36CNY

  • Detail

38194-50-2SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 13, 2017

Revision Date: Aug 13, 2017

1.Identification

1.1 GHS Product identifier

Product name sulindac

1.2 Other means of identification

Product number -
Other names Sudac

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:38194-50-2 SDS

38194-50-2Relevant articles and documents

Shuman et al.

, p. 1914 (1977)

Enantioselective synthesis of Sulindac

Maguire,Papot,Ford,Touhey,O'Connor,Clynes

, p. 41 - 44 (2001)

A highly enantioselective synthesis of Sulindac, a non-steroidal anti-inflammatory, is reported using the asymmetric Kagan sulfoxidation as key step.

Design, synthesis, and biological evaluation of novel sulindac derivatives as partial agonists of PPARγ with potential anti-diabetic efficacy

Huang, Fengyu,Zeng, Zhiping,Zhang, Weidong,Yan, Zhiqiang,Chen, Jiayun,Yu, Liangfa,Yang, Qian,Li, Yihuan,Yu, Hongyu,Chen, Junjie,Wu, Caisheng,Zhang, Xiao-kun,Su, Ying,Zhou, Hu

, (2021/06/22)

Peroxisome proliferator-activated receptor gamma (PPARγ) is a valuable drug target for diabetic treatment and ligands of PPARγ have shown potent anti-diabetic efficacy. However, to overcome the severe side effects of current PPARγ-targeted drugs, novel PPARγ ligands need to be developed. Sulindac, an identified ligand of PPARγ, is widely used in clinic as a non-steroidal anti-inflammatory drug. To explore its potential application for diabetes, we designed and synthesized a series of sulindac derivatives to investigate their structure-activity relationship as PPARγ ligand and potential anti-diabetic effect. We found that meta-substitution in sulindac's benzylidene moiety was beneficial to PPARγ binding and transactivation. Z rather than E configuration of the benzylidene double bond endowed derivatives with the selectivity of PPARγ activation. The indene fluorine is essential for binding and regulating PPARγ. Compared with rosiglitazone, compound 6b with benzyloxyl meta-substitution and Z benzylidene double bond weakly induced adipogenesis and PPARγ-targeted gene expression. However, 6b potently improved glucose tolerance in a diabetic mice model. Unlike rosiglitazone, 6b was devoid of apparent toxicity to osteoblastic formation. Thus, we provided some useful guidelines for PPARγ-based optimization of sulindac and an anti-diabetic lead compound with less side effects.

Green synthesis method of sulindac

-

, (2020/06/20)

The invention discloses a green synthesis method of sulindac and relates to the technical field of organic synthesis. The method comprises the following steps that: 6-fluoro-2-methyl indanone as a rawmaterial and cyanoacetic acid undergo a Knoevenagel reaction to obtain an intermediate 3, the intermediate 3 and p-methylthiobenzaldehyde undergo a Knoevenagel reaction to obtain an intermediate 4, the intermediate 4 undergoes a hydrolysis decarboxylation reaction to obtain an intermediate 5, and the intermediate 5 undergoes an oxidation reaction to obtain sulindac 1. Compared with an existing synthesis process, the process operation is greatly simplified, the raw material utilization rate and the process environmental protection property are improved, the total yield of sulindac reaches 80%or above, and the purity of sulindac reaches 99% or above.

Post a RFQ

Enter 15 to 2000 letters.Word count: 0 letters

Attach files(File Format: Jpeg, Jpg, Gif, Png, PDF, PPT, Zip, Rar,Word or Excel Maximum File Size: 3MB)

1

What can I do for you?
Get Best Price

Get Best Price for 38194-50-2