(+)-Ketoconazole

Base Information

• Chemical Name: (+)-Ketoconazole
• CAS No.: 65277-42-1
• Molecular Formula: C26H28Cl2H4O4
• Molecular Weight: 531.439
• Hs Code.: 2941.90
• European Community (EC) Number: 265-667-4
• ICSC Number: 1700
• UN Number: 2811
• DSSTox Substance ID: DTXSID7029879,DTXSID901316748
• Nikkaji Number: J301.871G
• Wikipedia: Ketoconazole
• Wikidata: Q27121163
• NCI Thesaurus Code: C605
• RXCUI: 6135
• Pharos Ligand ID: P3T7AVNKGKBA
• Metabolomics Workbench ID: 56947
• ChEMBL ID: CHEMBL75
• Mol file: 65277-42-1.mol

Synonyms:Ketoconazole;Nizoral;R 41400;R-41400;R41,400;R41400

Chemical Property of (+)-Ketoconazole

Chemical Property:

• Appearance/Colour: White powder
• Vapor Pressure: 1.39E-22mmHg at 25°C
• Melting Point: 146 °C
• Refractive Index: -10.5 ° (C=0.4, CHCl3)
• Boiling Point: 753.4 °C at 760 mmHg
• PKA: pKa 3.25/6.22(H2O,t =25,I=0.025) (Uncertain)
• Flash Point: 409.4 °C
• PSA: 69.06000
• Density: 1.38 cm³
• LogP: 4.20870
• Storage Temp.: 2-8°C
• Solubility.: methanol: soluble50mg/mL
• Water Solubility.: Soluble in DMSO, ethanol, chloroform, water, and methanol.
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 7
• Exact Mass: 530.1487608
• Heavy Atom Count: 36
• Complexity: 735

Purity/Quality:

99% ^*data from raw suppliers

Ketoconazole ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T,N,F
• Statements: 25-36/37/38-23/24/25-50/53-48/22-60-39/23/24/25-11
• Safety Statements: 36-45-36/37/39-26-61-60-53-36/37-16-7

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antifungal Agents
• Canonical SMILES: CC(=O)N1CCN(CC1)C2=CC=C(C=C2)OCC3COC(O3)(CN4C=CN=C4)C5=C(C=C(C=C5)Cl)Cl
• Isomeric SMILES: CC(=O)N1CCN(CC1)C2=CC=C(C=C2)OC[C@H]3CO[C@](O3)(CN4C=CN=C4)C5=C(C=C(C=C5)Cl)Cl
• Recent ClinicalTrials: Ketoconazole in Treating Participants With Ongoing EGFR Inhibitor-Induced Rash
• Recent EU Clinical Trials: A phase 2, randomized, vehicle and ketoconazole-controlled, evaluator-blinded, study to explore the efficacy, pharmacodynamics and safety of omiganan 1.75% topical gel BID in patients with mild to moderate facial seborrheic dermatitis.
• Recent NIPH Clinical Trials: The elucidation of influence and mechanisms of antifungal drugs to skin disorders caused by molecular target drugs
• Inhalation Risk: A harmful concentration of airborne particles can be reached quickly when dispersed, especially if powdered.
• Effects of Long Term Exposure: The substance may have effects on the endocrine system and liver. Animal tests show that this substance possibly causes toxicity to human reproduction or development.
• Pharmacological Activity: (+)-Ketoconazole is an imidazole antifungal agent with some antibacterial activity. It may act by interfering with the permeability of the fungal cell membrane.
• Dosage Forms: Formulated into various dosage forms for oral and topical administration.; Ketoconazole shampoo is commonly used for antidandruff purposes in Europe and the USA.
• Chemical Stability: Ketoconazole is a weak base with two pKa values.; Susceptible to degradation, including oxidation and hydrolysis, especially in aqueous media if not properly formulated.
• Inhibition of Cytochrome P450-3A (CYP3A): Widely used as an inhibitor of human cytochrome P450-3A isoforms.; The kinetic mechanism of CYP3A inhibition by ketoconazole in human liver microsomes is not fully established.; Ketoconazole shows strong CYP3A inhibition, but variations exist among substrates in the potency of inhibition.
• Clinical Use and Adverse Effects: First broad-spectrum oral antifungal agent for systemic and superficial mycoses.; Associated with hepatotoxicity, leading to warnings from regulatory agencies.; Despite concerns, still used for conditions like Cushing's disease due to its efficacy in lowering circulating cortisol levels.; Adverse effects in healthy adults include local reactions like severe irritation, pruritus, and stinging.
• Monitoring and Management: The use of ketoconazole should be closely monitored, especially with liver enzyme monitoring, due to potential hepatotoxicity. Hepatotoxicity associated with ketoconazole use is usually mild and resolves after discontinuation of the drug.

Technology Process of (+)-Ketoconazole

There total 31 articles about (+)-Ketoconazole which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 80.0%

1-(2,4-dichlorophenyl)-2-(imidazol-1-yl)ethanone (46503-52-0) + (+/-)-1-acetyl-4-<4-(2,3-dihydroxypropoxy)phenyl>piperazine (94133-71-8) → ketoconazole (65277-42-1)

Guidance literature:

With trifluoroacetic acid; In dimethyl sulfoxide; toluene; for 16h; Reagent/catalyst; Temperature; Reflux;

Reference yield: 10.0%

1H-imidazole (288-32-4) + (2R,4S)-cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-<<4-(4-acetylpiperazin-1-yl)phenoxy>methyl>-1,3-dioxolane (142128-67-4) → ketoconazole (65277-42-1) + (2R,4S)-cis-2-(hydroxymethyl)-2-(2,4-dichlorophenyl)-4-<<4-(4-acetylpiperazin-1-yl)phenoxy>methyl>-1,3-dioxolane (142004-25-9)

Guidance literature:

With potassium carbonate; In N,N-dimethyl acetamide; for 4h; Heating;

DOI:10.1021/jm00093a015

Reference yield:

[cis-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl] 4-methyl-benzenesulfonate (134071-44-6) + N-acetyl-N'-(4-hydroxyphenyl)piperazine (67914-60-7,89929-31-7) → ketoconazole (65277-42-1)

Guidance literature:

With sodium hydride; In dimethyl sulfoxide; at 0 - 80 ℃;

DOI:10.1016/j.bmcl.2005.11.001

upstream raw materials:

1H-imidazole

(2R,4S)-cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-<<4-(4-acetylpiperazin-1-yl)phenoxy>methyl>-1,3-dioxolane

(2R,4R)-(+)-<2-(2,4-dichlorophenyl)-2-<(1H-imidazol-1-yl)methyl>-1,3-dioxolan-4-yl>methyl methanesulfonate

N-acetyl-N'-(4-hydroxyphenyl)piperazine

Downstream raw materials:

ketoconazole

Refernces

• 1、 -. "Preparation method of ketoconazole". . . Retrieved 2018/04/03.
• 2、 Ibrahim, Wan Aini Wan,Arsad, Siti Rosilah,Maarof, Hasmerya,Sanagi, Mohd Marsin,Aboul-Enein, Hassan Y.. "Chiral separation of four stereoisomers of ketoconazole drugs using capillary electrophoresis". . p. 223 - 227. Retrieved 2015/03/18.