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: Efinaconazole, (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol, is a white to off-white powder. Efinaconazole has three different polymorphic forms identified, namely, Form A (I), Form B (II), and Form C (III), and widely used commercially as Form A (I). In particular, polymorphic forms of efinaconazole are quasi-isostructural polymorphism; thus, they might exhibit high degrees of similarity in physical properties as a result of similar neighboring-shell interaction energies. Efinaconazole is practically insoluble in water, which may have an effect on the quality of topical solution.
• Uses: Efinaconazole, a clinically used antifungal agent, was developed under the trade name Jublia (10% topical solution). In October 2013, efinaconazole (also known as KP-103) was approved in Canada as a 10% topical solution for the treatment of onychomycosis. It was approved by the Food and Drug Administration (FDA) in 2014. Efinaconazole permeated the nail more efficiently than luliconazole, and the amount of efinaconazole in the middle and lowest layers was higher compared with that of luliconazole. Efinaconazole demonstrated antifungal activities at the concentrations in all of the nail layers.
• Mechanism of Action: Efinaconazole is a novel triazole antifungal ((2 R,3R)- 2-(2,4-difluorophenyl)- 3-(4-methylenepiperidin-1-yl)- 1-(1H-1,2,4-triazol-1-yl) butan-2-ol; EFN) which hinders the cytochrome P450 catalyst and results in obstruction of ergosterol biosynthetic pathway of the fungi which disturbs the membrane layer and development of organisms. It is an antifungal agent affirmed by the US Food and Drug Administration (FDA) in USA for the topical delivery in the treatment of onychomycosis. Efinaconazole shows lesser binding affinity to keratin and is discharged more quickly from keratin, thus results in advancement of nail permeation and retention. It shows 8–64 times more fungal activity towards fungi when compared to ciclopirox and itraconazole. Its high nail plate penetration and broad-spectrum antifungal activity, makes it effective and unique drug for the onychomycosis treatment.

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

Asymmetric Catalytic Epoxidation of Terminal Enones for the Synthesis of Triazole Antifungal Agents

10.1021/acs.orglett.1c02588

The research focuses on the development of an efficient and enantioselective catalytic asymmetric epoxidation reaction of α-substituted vinyl ketones, which are key intermediates for the synthesis of various triazole antifungal agents. The purpose of this study was to create a concise and efficient method for constructing optically active epoxides with consecutive chiral carbon centers, a challenging task in the field of antifungal drug synthesis. The researchers successfully employed a chiral N,N′-dioxide/ScIII complex as the chiral catalyst and 35% aqueous hydrogen peroxide as the oxidant, achieving high yields and good enantioselectivities. This method not only provided a highly efficient and enantioselective route for the synthesis of antifungal agents such as isavuconazole and efinaconazole but also demonstrated the potential for synthesizing other potential antifungal agents. The study concluded that the chiral N,N′-dioxide/Sc(OTf)3 catalytic system was effective in the asymmetric epoxidation process, offering a wide range of α,α-disubstituted epoxides in good yields with high enantioselectivities.