5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid

• ChemBase ID: 1110
• Molecular Formular: C15H22O3
• Molecular Mass: 250.33338
• Monoisotopic Mass: 250.15689456
• SMILES: O(CCCC(C)(C)C(=O)O)c1c(ccc(c1)C)C
• Canonical SMILES: Cc1ccc(c(c1)OCCCC(C(=O)O)(C)C)C
• InChI: InChI=1S/C15H22O3/c1-11-6-7-12(2)13(10-11)18-9-5-8-15(3,4)14(16)17/h6-7,10H,5,8-9H2,1-4H3,(H,16,17)
• InChIKey: HEMJJKBWTPKOJG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid
• IUPAC Traditional name: gemfibrozil; 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid
• Brand Name: Apo-Gemfibrozil; Bolutol; Cholespid; Decrelip; Fibratol; Fibrocit; Gemfibril; Gemfibromax; Gemlipid; Gen-Fibro; Genlip; Gevilon; Hipolixan; Jezil; Lipozid; Lipur; Lopid; Novo-Gemfibrozil; Nu-Gemfibrozil
• Synonyms: 2,2-Dimethyl-5-(2,5-dimethylphenoxy)pentanoic acid; Gemfibrozil; Gemfibrozil; 5-(2,5-Dimethylphenoxy)-2,2-dimethylpentanoic acid; 5-(2,5-Dimethylphenoxy)-2,2-dimethylpentanoic Acid; 2,2-Dimethyl-5-(2,5-xylyloxy)valeric Acid; CI-7; Decrelip; Genlip; Gevilon; Lipozid; Emfib; Hipolixan; Lipur; Organolipid; Gemcor; Lopid; Jezil; Gen-Fibro

Database IDs

• CAS Number: 25812-30-0
• EC Number: 247-280-2
• MDL Number: MFCD00079335
• PubChem SID: 24895377; 160964573; 46508264
• PubChem CID: 3463

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.4168005
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 3.2735415
• LogD (pH = 7.4): 1.5146497
• Log P: 4.3896437
• Molar Refractivity: 71.8191 cm^3
• Polarizability: 27.933592 Å^3
• Polar Surface Area: 46.53 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.61
• LOG S: -3.95
• Solubility (Water): 2.78e-02 g/l

PROPERTIES

Physical Property

• Solubility: 10 mg/mL (in base); Chloroform; Ethyl Acetate; Hexane
• Apperance: White Solid
• Melting Point: 61-63°C
• Hydrophobicity(logP): 3.4

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• Storage Warning: IRRITANT
• RTECS: YV7120000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22
• Safety Statements: 36
• TSCA Listed: false
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves

Pharmacology Properties

• Mechanism of Action: Increases activity of Peroxisome proliferator-activated receptor-alpha (PPAR-alpha)

Product Information

• Salt Data: Free Base
• Suitability: suitable for 1694 per US EPA
• Application(s): Antihyperlipidaemic drug

DETAILS

DrugBank - DB01241

• Drug Groups: approved
• Description: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [PubChem]
• Indication: For treatment of adult patients with very high elevations of serum triglyceride levels (types IV and V hyperlipidemia) who are at risk of developing pancreatitis (inflammation of the pancreas) and who do not respond adequately to a strict diet.
• Pharmacology: Gemfibrozil, a fibric acid antilipemic agent similar to clofibrate, is used to treat hyperlipoproteinemia and as a second-line therapy for type IIb hypercholesterolemia. It acts to reduce triglyceride levels, reduce VLDL levels, reduce LDL levels (moderately), and increase HDL levels (moderately).
• Toxicity: Oral, mouse: LD₅₀ = 3162 mg/kg. Symptoms of overdose include abdominal cramps, diarrhea, joint and muscle pain, nausea, and vomiting.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Gemfibrozil mainly undergoes oxidation of a ring methyl group to successively form a hydroxymethyl and a carboxyl metabolite.
• Absorption: Well absorbed from gastrointestinal tract (within 1-2 hours).
• Half Life: 1.5 hours
• Protein Binding: 95%
• Elimination: Approximately seventy percent of the administered human dose is excreted in the urine, mostly as the glucuronide conjugate, with less than 2% excreted as unchanged gemfibrozil.
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1729

Research Area: Cardiovascular Disease
Biological Activity:
Gemfibrozil (Lopid) is an oral drug used to lower lipid levels. It belongs to a group of drugs known as fibrates. Increases activity of Peroxisome proliferator-activated receptor-alpha (PPARα) ’transcription factor ligand’ , a receptor that is involved in metabolism of carbohydrates and fats, as well as adipose tissue differentiation. This increase in the synthesis of lipoprotein lipase thereby increases the clearance of triglycerides. [1]

Sigma Aldrich - G9518

Biochem/physiol Actions
Selectively increases Apolipoprotein A-I levels.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. G9518.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - G305750

A serum lipid regulating agent used as an antihyperlipoproteinemic.

REFERENCES

• www.bentham.org/prc/samples/prc1-1/Higashi.pdf
• Kissebach, A.H., et al.: Atherosclerosis, 24, 199 (1976)
• Lewis, J.E., et al.: Pract. Cardiol., 9, 99 (1976)
• Rubins, H.B., et al.: N. Engl. J. Med., 341, 410 (1999)
• U.S. Pat., 1973, 3 707 566; CA, 78, 58105q, (synth)
• Creger, P.L. et al., Proc. R. Soc. Med., (Suppl. 2), 1976, 69, 1, (pharmacol, metab, tox)
• U.S. Pat., 1979, 4 126 637; CA, 90, 121021z, (synth)
• Glueck, C., Am. J. Cardiol., 1983, 52, 31, (rev)
• Abraham, D.J. et al., J. Med. Chem., 1984, 27, 967, (synth, props)
• Todd, P.A. et al., Drugs, 1988, 36, 314, (rev)
• Zimetbaum, P. et al., J. Clin. Pharmacol., 1991, 31, 25, (pharmacol, rev)
• Peroxisomes: Biology and Importance in Toxicology and Medicine, (Eds. Gibson, G. et al), Taylor and Francis, 1993, (tox)
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 7th edn., Akademie-Verlag, 1994, 4802, (synonyms)
• Alegret, M. et al., Br. J. Pharmacol., 1995, 114, 1351, (pharmacol)
• Spencer, C.M. et al., Drugs, 1996, 51, 982, (rev, pharmacol)
• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 1273
• Barter, P.J., J. Drug Eval. Cardiovasc. Med., 2002, 1, 13-39, (rev)
• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, GCK300