(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one

• ChemBase ID: 848
• Molecular Formular: C24H21F2NO3
• Molecular Mass: 409.4252464
• Monoisotopic Mass: 409.14894998
• SMILES: Fc1ccc(N2[C@@H]([C@@H](CC[C@H](O)c3ccc(F)cc3)C2=O)c2ccc(O)cc2)cc1
• Canonical SMILES: Oc1ccc(cc1)[C@@H]1[C@@H](CC[C@@H](c2ccc(cc2)F)O)C(=O)N1c1ccc(cc1)F
• InChI: InChI=1S/C24H21F2NO3/c25-17-5-1-15(2-6-17)22(29)14-13-21-23(16-3-11-20(28)12-4-16)27(24(21)30)19-9-7-18(26)8-10-19/h1-12,21-23,28-29H,13-14H2/t21-,22+,23-/m1/s1
• InChIKey: OLNTVTPDXPETLC-XPWALMASSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one
• IUPAC Traditional name: ezetimibe
• Brand Name: Ezedoc; Zetia; Ezetrol
• Synonyms: (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one; Ezetimibe; Zetia; Ezetrol

Database IDs

• CAS Number: 163222-33-1
• MDL Number: MFCD00937872
• PubChem SID: 160964311; 46507625
• PubChem CID: 150311

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.484299
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 4.559083
• LogD (pH = 7.4): 4.555587
• Log P: 4.559128
• Molar Refractivity: 108.8617 cm^3
• Polarizability: 41.585533 Å^3
• Polar Surface Area: 60.77 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 4.14
• LOG S: -4.68
• Solubility (Water): 8.46e-03 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 3.958; 4.5

Safety Information

• Storage Condition: -20°C

Product Information

• Purity: 95%
• Salt Data: Free Base

DETAILS

DrugBank - DB00973

• Drug Groups: approved
• Description: Ezetimibe is an anti-hyperlipidemic medication which is used to lower cholesterol levels. Specifically, it appears to bind to a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells as well as in hepatocytes.
• Indication: For use as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia.
• Pharmacology: Ezetimibe is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Ezetimibe, administered alone is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia. It is also used in combination therapy with HMG-CoA reductase inhibitors. Ezetimibe has a mechanism of action that differs from those of other classes of cholesterol-reducing compounds (HMG-CoA reductase inhibitors, bile acid sequestrants, fibric acid derivatives, and plant stanols). Ezetimibe does not inhibit cholesterol synthesis in the liver, or increase bile acid excretion but instead localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of HMG-CoA reductase inhibitors.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic, intestinal wall
• Half Life: 22 hours
• Protein Binding: >90%
• Elimination: Ezetimibe is primarily metabolized in the small intestine and liver via glucuronide conjugation (a phase II reaction) with subsequent biliary and renal excretion. In humans, ezetimibe is rapidly metabolized to ezetimibe-glucuronide.
• References: Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1655

Research Area: Cardiovascular Disease
Biological Activity:
Ezetimibe (Zetia) is a compound that lowers cholesterol. Ezetimibe (Zetia) acts by decreasing cholesterol absorption in the intestine. Ezetimibe (Zetia) may be used alone, when other cholesterol-lowering medications are not tolerated, or together with statins when statins alone do not control cholesterol. Ezetimibe localises at the brush border of the small intestine, where ezetimibe (Zetia) inhibits the absorption of cholesterol from the intestine. Specifically, ezetimibe (Zetia) appears to bind to a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells as well as in hepatocytes. [1]

REFERENCES

• Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31. Pubmed
• http://en.wikipedia.org/wiki/Ezetimibe