Efinaconazole

Base Information

• Chemical Name: Efinaconazole
• CAS No.: 164650-44-6
• Molecular Formula: C18H22F2N4O
• Molecular Weight: 348.39904
• European Community (EC) Number: 813-597-5
• UNII: J82SB7FXWB
• DSSTox Substance ID: DTXSID40167787
• Nikkaji Number: J1.186.659J
• Wikipedia: Efinaconazole
• Wikidata: Q21011225
• NCI Thesaurus Code: C97998
• RXCUI: 1539753
• Metabolomics Workbench ID: 152104
• ChEMBL ID: CHEMBL2103877
• Mol file: 164650-44-6.mol

Synonyms:efinaconazole;Jublia;KP 103;KP-103;KP103

Chemical Property of Efinaconazole

Chemical Property:

• Boiling Point: 512.2±60.0 °C(Predicted)
• PKA: 12.11±0.29(Predicted)
• PSA: 54.18000
• Density: 1.26±0.1 g/cm3(Predicted)
• LogP: 2.42250
• Storage Temp.: -20°C
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 348.17616766
• Heavy Atom Count: 25
• Complexity: 470

Purity/Quality:

99.0% ^*data from raw suppliers

Efinaconazole ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C(CN1C=NC=N1)(C2=C(C=C(C=C2)F)F)O)N3CCC(=C)CC3
• Isomeric SMILES: C[C@H]([C@](CN1C=NC=N1)(C2=C(C=C(C=C2)F)F)O)N3CCC(=C)CC3
• Recent ClinicalTrials: Safety and Pharmacokinetics of Efinaconazole Topical Solution in Subjects With Mild to Severe Onychomycosis
• Recent NIPH Clinical Trials: The examination of effectiveness and safety ofEfinaconazole
• Description: In October 2013, efinaconazole (also known as KP-103) was approved in Canada as a 10% topical solution for the treatment of onychomycosis. Like other azole antifungal agents, efinaconazole acts by disrupting fungal cell membranes through inhibition of sterol 14α-demethylase, an enzyme involved in the biosynthesis of ergosterol, which is a key component of the fungal cell membrane. Efinaconazole has potent antifungal activity against clinical isolates of dermatophytes, including Trichophyton mentagrophyes (MIC80 =0.125 μg/mL) and Trichophyton rubrum (MIC80 =0.25 μg/mL), as well as against Candida and Malassezia species. Unlike other antifungal agents, efinaconazole retains activity in the presence of keratin, indicating that more unbound drug is available at the site of action. Efinaconazole is efficacious in guinea-pig models of fungal infection. Efinaconazole is prepared by reaction of an epoxide intermediate with 4-methylenepiperidine. Efinaconazole is a broad-spectrum triazole antifungal agent with activity against Acremonium, Aspergillus, Candida, Cryptococcus, Epidermophyton, Fusarium, Microsporum, Paecilomyces, Pseudallescheria, Scopulariopsis, Trichophyton, and Trichosporon. It inhibits the growth of T. rubrum and T. mentagrophytes clinical isolates with MIC values ranging from ≤2.0 to 60 ng/ml and of C. albicans isolates with MIC values ranging from ≤0.5 to >250 ng/ml. Efinaconazole inhibits sterol 14α-demethylase, which arrests ergosterol biosynthesis at the fungal membrane. It inhibits ergosterol biosynthesis in T. mentagrophytes and C. albicans with IC50 values of 7.0 and 0.40 ng/ml, respectfully. Topical formulations containing efinaconazole have been used for the treatment of onychomycosis.
• Uses: Efinaconazole has been used as:a topical anti-onychomycosis drug to determine its effects on Trichophyton rubrum and Trichophyton interdigitaleas an anti-fungal agent to study its permeability into the nail lysatesas an anti-fungal agent to study its effects on Candida africana and Candida dubliniensis

Technology Process of Efinaconazole

There total 69 articles about Efinaconazole 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: 98.0%

4-methylene piperidine (148133-82-8) + 1-(((2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)-methyl)-1H-1,2,4-triazole (124627-86-7,132563-70-3,132563-77-0,135270-07-4,135270-10-9,135270-13-2,141611-70-3,127000-90-2) → (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)-butane-2-ol (164650-45-7,164650-44-6)

Guidance literature:

With strontium perchlorate hydrate; In acetonitrile; at 90 ℃; for 1.5h; Reagent/catalyst; Solvent; Temperature;

Reference yield: 98.0%

para-toluenesulphonic acid efinaconazole salt (164650-61-7) → (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)-butane-2-ol (164650-45-7,164650-44-6)

Guidance literature:

With sodium hydroxide; In ethanol; water; at 0 - 5 ℃; pH=11;

Reference yield: 96.0%

1-(((2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)-methyl)-1H-1,2,4-triazole (124627-86-7,132563-70-3,132563-77-0,135270-07-4,135270-10-9,135270-13-2,141611-70-3,127000-90-2) + 4-methylenepiperidine monohydrochloride (144230-50-2) → (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)-butane-2-ol (164650-45-7,164650-44-6)

Guidance literature:

4-methylenepiperidine monohydrochloride; With sodium hydroxide; In acetonitrile; at 25 ℃; for 0.5h;

1-(((2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)-methyl)-1H-1,2,4-triazole; With lithium iodide; In acetonitrile; at 85 ℃; for 5h; Reagent/catalyst;

upstream raw materials:

4-methylene piperidine

(2S,3R)-2-(2,4-difluorophenyl)-3-methyl-2-<(1H-1,2,4-triazol-1-yl)methyl>oxirane

(4-(chloromethyl)piperidin-1-yl)(phenyl)methanone

N-benzoyl-4-methylenepiperidine

Refernces

• 1、 Zhu, Fuqiang,Xie, Yuanchao,Zhang, Jian,Tian, Guanghui,Qin, Hongjian,Yang, Xiaojun,Hu, Tianwen,He, Yang,Aisa, Haji A.,Shen, Jingshan. "A Facile Epoxide Aminolysis Promoted by (t-BuO)2Mg and Its Application to the Synthesis of Efinaconazole". . p. 625 - 632. Retrieved 2018.
• 2、 -. "PREPARATION METHOD FOR EFINACONAZOLE". Paragraph 0031-0048. . Retrieved 2021/11/26.
• 3、 -. "METHOD FOR PREPARATION OF EFINACONAZOLE IN IONIC LIQUID MEDIUM". Paragraph 0079; 0095-0102. . Retrieved 2021/01/29.