164650-44-6 Usage
Description
Different sources of media describe the Description of 164650-44-6 differently. You can refer to the following data:
1. 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.
2. 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.
Originator
Kaken Pharmaceuticals (Japan)
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
Definition
ChEBI: A member of the class of triazoles that is butan-2-ol which is substituted at positions 1, 2, and 3 by 1,2,4-triazol-1-yl, 2,4-difluorophenyl, and 4-methylenepiperidin-1-yl groups, respectively (the 2R,3R stereoisomer). It
is an antifungal drug used for the topical treatment of onychomycosis (a nail infection caused mainly by dermatophytes).
Brand name
Jublia
Biochem/physiol Actions
Efinaconazole is a triazole antifungal drug approved clinically for the treatment of nail fungus (Onychomycosis). It inhibits sterol biosynthesis by inhibition of cytochrome P450 14α-demethylase, an enzyme in the sterol biosynthesis pathway that leads from lanosterol to ergosterol. Efinaconazole has better nail penetration, so is more effective than other topical agents and as effective as oral medication for nail fungus.
Synthesis
Commercially available (R)-methyl lactate (55) was first converted
to THP protected alcohol 57 in 4 steps and 78% yield via
morpholino amide 56. Grignard displacement of the morpholine
afforded ketone 58 in 81% yield. Next, ketone 58 was epoxidized
by means of the Corey ylide followed by ring-opening of the epoxide
by triazole which had been activated by exposure to sodium tbutoxide.
Finally, subjection to methanesulfonic acid furnished
diol 59 in 51% yield as the corresponding mesylate salt. Diol 59
was then converted to epoxide 60 through the use of mesyl chloride
and triethylamine in 78% yield and >99% ee. Finally, treatment of epoxide 60 with 4-methylene piperidine–HBr in the presence of
lithium hydroxide afforded efinaconazole (VIII) in 87% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 164650-44-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,4,6,5 and 0 respectively; the second part has 2 digits, 4 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 164650-44:
(8*1)+(7*6)+(6*4)+(5*6)+(4*5)+(3*0)+(2*4)+(1*4)=136
136 % 10 = 6
So 164650-44-6 is a valid CAS Registry Number.
164650-44-6Relevant articles and documents
Identification, synthesis, and control of efinaconazole impurities
Zhu, Fuqiang,Zhang, Jian,Xiamuxi, Hainimu,Chen, Weiming,Hu, Tianwen,Yang, Xiaojun,Tian, Guanghui,Ni, Runyan,Li, Jian,Suo, Jin,Xie, Yuanchao,Shen, Jingshan,Aisa, Haji A.,He, Yang
, p. 438 - 441 (2018)
Impurities A-F were observed, identified, and confirmed during the efinaconazole production process. The possible formation pathways of the mentioned impurities were understood, and thereafter, a controlling strategy was established by locating the proper process parameters with the consideration of efficient cost and less waste as well. This impurity investigation is also essential for quality control of consistently delivering of qualified efinaconazole API.
Asymmetric Catalytic Epoxidation of Terminal Enones for the Synthesis of Triazole Antifungal Agents
Feng, Xiaoming,He, Qianwen,Liu, Xiaohua,Zhang, Dong,Zhang, Fengcai
supporting information, p. 6961 - 6966 (2021/09/11)
An enantioselective epoxidation of α-substituted vinyl ketones was realized to construct the key epoxide intermediates for the synthesis of various triazole antifungal agents. The reaction proceeded efficiently in high yields with good enantioselectivities by employing a chiral N,N′-dioxide/ScIII complex as the chiral catalyst and 35% aq. H2O2 as the oxidant. It enabled the facile transformation for optically active isavuconazole, efinaconazole, and other potential antifungal agents.
PREPARATION METHOD FOR EFINACONAZOLE
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Paragraph 0031-0048, (2021/11/26)
The present invention provides a preparation method for Efinaconazole, comprising the following steps: in the presence of a bromide and a base, subjecting (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oxirane and an inorganic a
METHOD OF PRODUCING 1-TRIAZOLE-2-BUTANOL DERIVATIVES
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Paragraph 0039-0066, (2018/05/15)
PROBLEM TO BE SOLVED: To provide a novel method of producing 1-triazole-2-butanol derivatives useful as pharmaceuticals. SOLUTION: A method of producing a 1-triazole 2-butanol derivative represented by formula (1) comprises reacting a compound represented by formula (2) with 4-methylenepiperidine (3) in the presence of a metal salt (excluding lithium salts). SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT