164650-44-6 Usage
Description
KP 103, also known as Efinaconazole, is a broad-spectrum triazole antifungal agent with potent activity against various fungal species. It acts by inhibiting sterol 14α-demethylase, an enzyme involved in the biosynthesis of ergosterol, which is a key component of the fungal cell membrane. Efinaconazole is effective against dermatophytes, Candida, and Malassezia species, and retains its activity in the presence of keratin, making it more available at the site of action.
Used in Antifungal Applications:
KP 103 is used as a topical antifungal agent for the treatment of onychomycosis, a nail infection caused mainly by dermatophytes. It is effective against clinical isolates of dermatophytes, such as Trichophyton rubrum and Trichophyton interdigitale, as well as against Candida africana and Candida dubliniensis.
Used in Pharmaceutical Industry:
KP 103 is used as an active pharmaceutical ingredient in the development of antifungal medications, specifically for the treatment of onychomycosis. It is marketed under the brand name Jublia, a 10% topical solution approved in Canada in October 2013.
Used in Research and Development:
KP 103 is used in scientific studies to investigate its permeability into nail lysates and its effects on various fungal species, contributing to the understanding of its antifungal properties and potential applications in treating fungal infections.
Originator
Kaken Pharmaceuticals (Japan)
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
