2-{5-fluoro-1-[(4-methanesulfinylphenyl)methylidene]-2-methyl-1H-inden-3-yl}acetic acid

• ChemBase ID: 487
• Molecular Formular: C20H17FO3S
• Molecular Mass: 356.4105832
• Monoisotopic Mass: 356.08824362
• SMILES: S(=O)(c1ccc(C=C2C(=C(c3c2ccc(F)c3)CC(=O)O)C)cc1)C
• Canonical SMILES: OC(=O)CC1=C(C)C(=Cc2ccc(cc2)S(=O)C)c2c1cc(F)cc2
• InChI: InChI=1S/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)
• InChIKey: MLKXDPUZXIRXEP-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-{5-fluoro-1-[(4-methanesulfinylphenyl)methylidene]-2-methyl-1H-inden-3-yl}acetic acid; 2-[(1Z)-5-fluoro-1-[(4-methanesulfinylphenyl)methylidene]-2-methyl-1H-inden-3-yl]acetic acid
• IUPAC Traditional name: sulindac
• Brand Name: Clinoril
• Synonyms: Sulindac; Clinoril; Aflodac; Sulreuma; (Z)-2-(5-fluoro-2-methyl-1-(4-(methylsulfinyl)benzylidene)-1H-inden-3-yl)acetic acid; Sulindac; Z-5-Fluoro-2-methyl-1-[p-(methlsulfinyl)benzylidene]indene-3-acetic acid; MK-231; (1Z)-5-Fluoro-2-methyl-1-[(4-(methylsulfinyl)phenyl]methylene]-1H-indene-3-acetic Acid; cis-5-Fluoro-2-methyl-1-[(p-methylsulfinyl)benzylidenyl]indene-3-acetic Acid; Algocetil; Arthrocine; Artribid; Citireuma; Clisundac; Imbaral; MK 231; Mobilin; Reumofil; Reumyl; Sudac; Sulindac; Sulindac sulfoxide; Sulinol; cis-Sulindac; (Z)-5-氟-2-甲基-1-[4-(甲亚硫酰苯基)亚甲基]-1H-茚-3-醋酸; 舒林酸

Database IDs

• CAS Number: 38194-50-2
• EC Number: 253-819-2
• MDL Number: MFCD00599589
• PubChem SID: 24899604; 160963950; 24277737
• PubChem CID: 5352

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.090206
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 1.5030619
• LogD (pH = 7.4): -0.17891507
• Log P: 2.9261546
• Molar Refractivity: 99.5588 cm^3
• Polarizability: 37.41637 Å^3
• Polar Surface Area: 54.37 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.96
• LOG S: -4.15
• Solubility (Water): 2.51e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Pactically insoluble in water below pH 4.5, but very soluble as the sodium salt or in buffers of pH 6 or higher (3000 mg/L).
• Apperance: Yellowish Orange Solid
• Melting Point: 182-185°C
• Hydrophobicity(logP): 3.5

Safety Information

• Storage Condition: -20°C; -20°C Freezer; Room Temperature (15-30°C)
• RTECS: NK8226000
• European Hazard Symbols: Harmful (Xn)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 3
• Risk Statements: 63-22-42/43; R:22
• Safety Statements: S:36/37/39
• GHS Pictograms: GHS06; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H301-H317-H334-H361
• GHS Precautionary statements: P261-P280-P301 + P310-P342 + P311
• Personal Protective Equipment: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3

Pharmacology Properties

• Gene Information: human ... ALB(213); human ... ALB(213), PTGS2(5743)

Product Information

• Purity: ≥99%; ≥98.0%; 95+%
• Salt Data: Free Base
• Suitability: meets USP testing specifications

DETAILS

MP Biomedicals - 02195864

Purity: >99%
Non-steroidal anti-inflammatory which inhibits cyclooxygenase and prostaglandin synthesis. Causes adenoma regression by apoptotic mechanism and induces apoptosis in HT-29 cells at levels which affect cell proliferation, morphology and cell phase distribution.

DrugBank - DB00605

• Drug Groups: approved
• Description: Sulindac is a nonsteroidal anti-inflammatory agent (NSAIA) of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIAs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in vivo to an active sulfide compound by liver enzymes. The sulfide metabolite then undergoes enterohepatic circulation; it is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIA's except for drugs of the cyclooxygenase-2 (COX-2) inhibitor class. The exact mechanism of its NSAIA properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.
• Indication: For acute or long-term use in the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis), and acute gouty arthritis.
• Pharmacology: Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.
• Toxicity: Acute oral toxicity (LD₅₀) in rats is 264 mg/kg. Cases of overdose have been reported and rarely, deaths have occurred. The following signs and symptoms may be observed following overdose: stupor, coma, diminished urine output and hypotension.
• Affected Organisms: Humans and other mammals
• Biotransformation: Undergoes two major biotransformations: reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Sulindac and its sulfide and sulfone metabolites undergo extensive enterohepatic circulation. Available evidence indicates that the biological activity resides with the sulfide metabolite. Side chain hydroxylation and hydration of the double bond also occur.
• Absorption: Approximately 90% absorbed in humans following oral administration.
• Half Life: The mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours.
• Protein Binding: At 1 mcg/ml concentrations, approximately 93% sulindac and 98% of its sulfide metabolite are bound to human serum albumin.
• Elimination: Sulindac is excreted in rat milk; concentrations in milk were 10 to 20% of those levels in plasma. It is not known if sulindac is excreted in human milk. Approximately 50% of the administered dose of sulindac is excreted in the urine with the conjugated sulfone metabolite accounting for the major portion. Hepatic metabolism is an important elimination pathway.
• Clearance: * Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S2007

Research Area: Neurological Disease
Biological Activity:
Sulindac (Clinoril) is a non-steroidal anti-inflammatory drug of the arylalkanoic acid class. Like other NSAIDs, it is useful in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene that is converted in the body to an active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. [1]

InterBioScreen - BB_SC-1128

(Z)-isomer

Sigma Aldrich - S8139

Biochem/physiol Actions
非甾体抗炎药；COX-1 的选择性抑制剂。
Application
Treatment of human colorectal cancer cell lines induces MRP1 and MRP3 but not other members of the MRP family. Reported to significantly increase the cytotoxicity of the anthracyclines (doxorubicin, daunorubicin and epirubicin), as well as teniposide, VP-16 and vincristine.

Sigma Aldrich - S4429

Biochem/physiol Actions
非甾体抗炎药；COX-1 的选择性抑制剂。

Toronto Research Chemicals - S699215

Sulindac is a non-steroidal anti-inflammatory drug.

REFERENCES

• http://www.drugbank.ca/drugs/DB00605
• Bjorkman., et al.: Am. J. Med., 105, 17S (1998)
• Thakur, et al.: Am. J. Hypertens., 12, 925 (1998)