65472-88-0 Usage
Description
Naftifine, also known as Naftin, is a synthetic allylamine derivative used as a topical antifungal agent. It works by blocking squalene 2,3-epoxidase, which leads to increased cell membrane permeability and cell death. Naftifine is structurally and pharmacologically related to terbinafine and has some anti-inflammatory properties due to its ability to alter chemotaxis by polymorphonucleocytes.
Uses
Used in Pharmaceutical Industry:
Naftifine is used as a topical antifungal agent for the treatment of fungal skin infections. It is most effective against dermatophytes, moderately active against molds, and less active against yeasts, including C. albicans. The drug is only permitted to be used externally and superficially, with a broad spectrum of action against dermatophytes and candida infections. It is believed that the fungicide activity of Naftifine is based on its ability to inhibit the fungal enzyme squalene epoxidase, thus lowering the concentration of ergosterol. The corresponding enzyme in mammals is inhibited significantly less.
Used in Chemical Synthesis:
(E)-Naftifine is used as an intermediate in synthesizing Naftifine N-Oxide (N213110), which is an impurity or metabolite of Naftifine Hydrochloride (N213100), an allylamine antifungal agent.
Brand Name:
Naftifine is commercially available under the brand name Naftin, manufactured by Merz.
Originator
Naftifine,Sandoz (Novartis)
Indications
Naftifine (Naftin) is a synthetic allylamine derivative topical antifungal agent
that works by blocking squalene 2,3-epoxidase, resulting in increased cell
membrane permeability and cell death. It is structurally and pharmacologically
related to terbinafine. It also has some antiinflammatory properties that
may be due to its ability to alter chemotaxis by polymorphonucleocytes. It is
most effective against dermatophytes, moderately active against molds, and
less active against yeasts, including C. albicans.
Manufacturing Process
To a mixture of 1.42 g of methyl-(1-naphthylmethyl)amine hydrochloride,
2.89 g of sodium carbonate and 10 ml of dimethylformamide is added, at
room temperature, 1.25 g of cinnamyl chloride, dropwise. After 18 hours
stirring, at room temperature, the mixture is filtered and the filtrate is
evaporated in vacuo. The residue is dissolved in toluene and, after drying over
sodium sulphate, evaporated to obtain the trans-N-(cinnamylmethyl)-Nmethyl-(1-naphthylmethyl)amine compound, boiling point 162-167°C/0.015
Torr.The free base may be converted, with isopropanolic hydrogen chloride
solution, into the hydrochloride form, melting point 177°C (from propanol).
Therapeutic Function
Antifungal
Synthesis Reference(s)
Journal of Medicinal Chemistry, 29, p. 112, 1986 DOI: 10.1021/jm00151a019Tetrahedron Letters, 25, p. 2535, 1984 DOI: 10.1016/S0040-4039(01)81224-7
Pharmaceutical Applications
A topical antifungal used as a 1% cream for the treatment
of dermatophytoses, including tinea pedis, tinea corporis and
tinea cruris.
Clinical Use
Naftifine was the first allyl amine to be discovered and marketed. It is subject to extensive first-pass metabolism to be orally active and, consequently, is only available in topical preparations. The widest use of naftifine is against various tinea infections of the skin.
Synthesis
Naftifine, (E)-N-methyl-N-(3-phenyl-2-propenyl)-1-naphthalinmethanamine
(35.3.1), is synthesized by alkylating N-methyl-(1-naphthylmethyl)-amine with cinnamyl
chloride in the presence of sodium carbonate.
Check Digit Verification of cas no
The CAS Registry Mumber 65472-88-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,5,4,7 and 2 respectively; the second part has 2 digits, 8 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 65472-88:
(7*6)+(6*5)+(5*4)+(4*7)+(3*2)+(2*8)+(1*8)=150
150 % 10 = 0
So 65472-88-0 is a valid CAS Registry Number.
InChI:InChI=1/C21H21N.ClH/c1-22(16-8-11-18-9-3-2-4-10-18)17-20-14-7-13-19-12-5-6-15-21(19)20;/h2-15H,16-17H2,1H3;1H/b11-8+;
65472-88-0Relevant articles and documents
THE BORONIC ACID MANNICH REACTION: A NEW METHOD FOR THE SYNTHESIS OF GEOMETRICALLY PURE ALLYLAMINES
Petasis, Nicos A.,Akritopoulou, Irini
, p. 583 - 586 (1993)
Reaction of vinyl boronic acids with the adducts of secondary amines and paraformaldehyde gives tertiary allylamines with the same geometry.This simple and practical method was used for the synthesis of geometrically pure naftifine, a potent antifungal agent.
N -Butylpyrrolidone (NBP) as a non-toxic substitute for NMP in iron-catalyzed C(sp2)-C(sp3) cross-coupling of aryl chlorides
Bisz, Elwira,Koston, Martina,Szostak, Michal
supporting information, p. 7515 - 7521 (2021/10/12)
Although iron catalyzed cross-coupling reactions show extraordinary promise in reducing the environmental impact of more toxic and scarce transition metals, one of the main challenges is the use of reprotoxic NMP (NMP = N-methylpyrrolidone) as the key ligand to iron in the most successful protocols in this reactivity platform. Herein, we report that non-toxic and sustainable N-butylpyrrolidone (NBP) serves as a highly effective substitute for NMP in iron-catalyzed C(sp2)-C(sp3) cross-coupling of aryl chlorides with alkyl Grignard reagents. This challenging alkylation proceeds with organometallics bearing β-hydrogens with efficiency superseding or matching that of NMP with ample scope and broad functional group tolerance. Appealing applications are demonstrated in the cross-coupling in the presence of sensitive functional groups and the synthesis of several pharmaceutical intermediates, including a dual NK1/serotonin inhibitor, a fibrinolysis inhibitor and an antifungal agent. Considering that the iron/NMP system has emerged as one of the most powerful iron cross-coupling technologies available in both academic and industrial research, we anticipate that this method will be of broad interest.
Oxidative Rearrangement of MIDA (N-Methyliminodiacetic Acid) Boronates: Mechanistic Insights and Synthetic Applications
Kaldas, Sherif J.,Tien, Chieh-Hung,Gomes, Gabriel Dos Passos,Meyer, Stephanie,Sirvinskas, Martynas,Foy, Hayden,Dudding, Travis,Yudin, Andrei K.
supporting information, p. 324 - 328 (2021/01/26)
Herein we report that coordinative hemilability allows the MIDA (N-methyliminodiacetic acid) nitrogen to behave as a nucleophile and intramolecularly intercept palladium π-allyl intermediates. A mechanistic investigation indicates that this rearrangement proceeds through an SN2-like displacement at tetrasubstituted boron to furnish novel DABN boronates. Oxidative addition into the N-C bond of the DABN scaffold furnishes borylated π-allyl intermediates that can then be trapped with a variety of nucleophiles, including in a three-component coupling.