142128-58-3

Basic information

• Product Name: (2R,4R)-Ketoconazole
• Synonyms: (2R,4R)-Ketoconazole
• CAS NO: 142128-58-3
• Molecular Weight: 531.439
• Mol File: 142128-58-3.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: (2R,4R)-Ketoconazole(CAS DataBase Reference)
• NIST Chemistry Reference: (2R,4R)-Ketoconazole(142128-58-3)
• EPA Substance Registry System: (2R,4R)-Ketoconazole(142128-58-3)

Safety Data

• Hazardous Substances Data: 142128-58-3(Hazardous Substances Data)

Usage

Description

(2R,4R)-Ketoconazole is a synthetic antifungal medication that is commonly used to treat a variety of fungal infections. It works by inhibiting the synthesis of ergosterol, a key component of fungal cell membranes, which leads to the disruption of the cell membrane and ultimately the death of the fungus. This effectively treats the infection and is available in various forms such as cream, shampoo, and tablets. It is generally well-tolerated when used as directed, but may cause side effects in some individuals and can interact with certain medications.

Uses

Used in Antifungal Treatments:
(2R,4R)-Ketoconazole is used as an antifungal agent for treating various fungal infections such as athlete's foot, ringworm, and jock itch. It is effective in inhibiting the synthesis of ergosterol, which is crucial for the integrity of fungal cell membranes, leading to the death of the fungus and clearing the infection.
Used in Pharmaceutical Industry:
(2R,4R)-Ketoconazole is used as a medication in the pharmaceutical industry for the treatment of fungal infections. It is available in different forms, including topical creams, shampoos, and oral tablets, providing flexibility in treatment options for patients. Its effectiveness in treating fungal infections makes it a valuable asset in the management of such conditions.
Used in Medication Formulation:
(2R,4R)-Ketoconazole is used in the formulation of various medications designed to combat fungal infections. Its versatility in different forms allows for targeted treatment, whether it be a localized application for skin infections or an oral administration for systemic infections. This makes it a key component in the development of antifungal medications.

Upstream product

• 65277-42-1 ketoconazole 
• 79156-75-5 1-(4-{4-[2-(2,4-dichloro-phenyl)-2-imidazol-1-ylmethyl-[1,3]dioxolan-4-ylmethoxy]-phenyl}-piperazin-1-yl)-ethanone 
• 2234-16-4 1-(2,4-dichlorophenyl)ethan-1-one 
• 82966-35-6 (2S,4S)-cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-<<<(4-methylphenyl)sulfonyl>oxy>methyl>-1,3-dioxolane 
• 2631-72-3 2,4-dichlorophenacyl bromide 
• 170210-49-8 cis-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-hydroxymethyl-1,3-dioxolane 
• 288-32-4 1H-imidazole 
• 142128-65-2 (2S,4R)-cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-<<4-(4-acetylpiperazin-1-yl)phenoxy>methyl>-1,3-dioxolane 
• 82966-35-6 (2R,4S)-trans-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-<<<(4-methylphenyl)sulfonyl>oxy>methyl>-1,3-dioxolane 
• 142128-66-3 (2R,4R)-trans-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-<<4-(4-acetylpiperazin-1-yl)phenoxy>methyl>-1,3-dioxolane 
• 38869-47-5 4-(p-methoxyphenyl)piperazine dihydrochloride 
• 38869-37-3 1-(4-hydroxy-phenyl)-piperazine dihydrobromide 
• 61397-61-3 trans-<2-(2,4-Dichlorophenyl)-2-<1H-imidazol-1-yl>methyl-(1,3-dioxolan-4-yl)>methyl methanesulfonate 
• 67914-60-7 N-acetyl-N'-(4-hydroxyphenyl)piperazine 

Downstream Products

• 1621914-33-7 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylpiperazine 
• 1621914-66-6 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylmethanesulfonylpiperazine 
• 1621914-63-3 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(thiophene-2-sulfonyl)piperazine 
• 1621914-65-5 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(1-methylimidazol-2-ylsulfonyl)piperazine 
• 1621914-34-8 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(ethanesulfonyl)piperazine 
• 1621914-35-9 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine 
• 1621914-36-0 1-(cyclopropanesulfonyl)-4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine 
• 1621914-73-5 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2-methoxyethanesulfonyl)piperazine 
• 1621914-75-7 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(oxane-4-sulfonyl)piperazine 
• 1621914-58-6 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-trifluoromethanesulfonylpiperazine 
• 1621914-69-9 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-difluoromethanesulfonylpiperazine 

Relevant articles and documents

A chiral enantioseparation generic strategy for anti-Alzheimer and antifungal drugs by short end injection capillary electrophoresis using an experimental design approach

The present study describes a generic strategy using capillary electrophoretic (CE) method for chiral enantioseparation of anti-Alzheimer drugs, namely, donepezil (DON), rivastigmine (RIV), and antifungal drugs, namely, ketoconazole (KET), Itraconazole (ITR), fluconazole (FLU), and sertaconazole (SRT) in which these drugs have different basic and acidic properties. Several modified cyclodextrins (CDs) were applied for enantioseparation of racemates such as highly sulfated α, γ CDs, hydroxyl propyl-β-CD, and Sulfobutyl ether-β-CD. The starting screening conditions consist of 50-mM phosphate-triethanolamine buffer at pH?2.5, an applied voltage of 15?kV, and a temperature of 25°C. The CE strategy implemented in the separation starts by screening prior to the optimization stage in which an experimental design is applied. The design of experiment (DOE) was based on a full factorial design of the crucial two factors (pH and %CD) at three levels, to make a total of nine (32) experiments with high, intermediate, and low values for both factors. Evaluation of the proposed strategy pointed out that best resolution was obtained at pH?2.5 for five racemates using low percentages of HS-γ-CD, while SBE-β-CD was the most successful chiral selector offering acceptable resolution for all the six racemates, with the best separation at low pH values and at higher %CD within 10-min runtime. Regression study showed that the linear model shows a significant lack of fit for all chiral selectors, anticipating that higher orders of the factors are most likely to be present in the equation with possible interactions.

Chiral separation of four stereoisomers of ketoconazole drugs using capillary electrophoresis

This work aimed to develop a chiral separation method of ketoconazole enantiomers using electrokinetic chromatography. The separation was achieved using heptakis (2, 3, 6- tri-O-methyl)-β-cyclodextrin (TMβCD), a commonly used chiral selector (CS), as it is relatively inexpensive and has a low UV absorbance in addition to an anionic surfactant, sodium dodecyl sulfate (SDS). The influence of TMβCD concentration, phosphate buffer concentration, SDS concentration, buffer pH, and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10mM phosphate buffer at pH2.5 containing 20mM TMβCD, 5mM SDS, and 1.0% (v/v) methanol with an applied voltage of 25 kV at 25 °C with a 5-s injection time (hydrodynamic injection). The four ketoconazole stereoisomers were successfully resolved for the first time within 17 min (total analysis time was 28 min including capillary conditioning). The migration time precision of this method was examined to give repeatability and reproducibility with RSDs ≤5.80% (n =3) and RSDs ≤8.88% (n =9), respectively.

Stereoisomers of ketoconazole: Preparation and biological activity

The four stereoisomers of the antifungal agent ketoconazole (1) were prepared and evaluated for their selectivity in inhibiting a number of cytochrome P-450 enzymes. Large differences in selectivity among the isomers were observed for inhibition of the cytochromes P-450 involved in steroid biosynthesis, whereas little differences was observed for inhibition of those associated with hepatic drug metabolism. The cis-(2S,4R) isomer 2 was the most effective against rat lanosterol 14α-demethylase, (2S,4R)-2 > (2R,4S)-4 >> (2R,4R)-3 = (2S,4S)-5, and progesterone 17α,20-lyase, (2S,4R)-2 >> (2S,4S)-5 > (2R,4R)-3 = (2R,4S)-4, whereas the cis-(2R,4S) isomer 4 was more effective against cholesterol 7α-hydroxylase, (2R,4S)-4 > (2S,4S)-5 > (2R,4R)-3 > (2S,4R)-2, and the trans-(2S,4S) isomer 5 was the most effective against aromatase, (2S,4R)-5 >> (2R,4R)-3 = (2R,4S)-4 > (2S,4R)-2. The cis- (2S,4R) and trans-(2R,4R) isomers 2 and 3 are equipotent in inhibiting corticoid 11β-hydroxylase and much more effective than their antipodes. Little selectivity was observed for inhibition of cholesterol side chain cleavage or xenobiotic hydroxylases. These data indicate that the affinity of azoles for cytochrome P-450 enzymes involved in steroid synthesis is highly dependent on the stereochemistry of the entire molecule, whereas binding to drug metabolizing enzymes is a less selective process.