91161-71-6

Basic information

• Product Name: Terbinafine hydrochloride
• Synonyms: LAMISIL;(e)-n-(6,6-dimethyl-2-hepten-4-ynyl)-n-methyl-1-naphthalenemethanamine;6-dimethyl-2-hepten-4-ynyl)-n-methyl-n-((e)-1-naphthalenemethanamin;sf-86-327;TERBINAFINE;trans-N-(6,6-Dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthylmethylamine;1-Naphthalenemethanamine, N-(2E)-6,6-dimethyl-2-hepten-4-ynyl-N-methyl-;N,6,6-Trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-yn-1-amine hydrochloride
• CAS NO: 91161-71-6
• Molecular Formula: C₂₁H₂₅N
• Molecular Weight: 291.44
• EINECS: 245-385-8
• Product Categories: Active Pharmaceutical Ingredients;Terbinafine;Inhibitors
• Mol File: 91161-71-6.mol
• Article Data: 20

Chemical Properties

• Melting Point: 203-205 °C
• Boiling Point: 417.9 °C at 760 mmHg
• Flash Point: 183.7 °C
• Appearance: /
• Density: 1.007g/cm³
• Vapor Pressure: 0Pa at 25℃
• Storage Temp.: 2-8°C
• Solubility: soluble in Methanol
• PKA: 6.92±0.50(Predicted)
• CAS DataBase Reference: Terbinafine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Terbinafine hydrochloride(91161-71-6)
• EPA Substance Registry System: Terbinafine hydrochloride(91161-71-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 91161-71-6(Hazardous Substances Data)

Usage

Description

Terbinafine hydrochloride, also known as Terbinafine (Lamisil), is a second-generation allylamine antifungal agent that is 10 to 100 times more potent in vitro compared to other antifungal drugs. It is fungicidal, making it more effective than fungistatic drugs like griseofulvin, ketoconazole, and itraconazole. Terbinafine hydrochloride acts by inhibiting squalene epoxidase, which leads to a decrease in the synthesis of ergosterol, an essential component of fungal cell membranes. Its high lipophilicity allows it to concentrate in the stratum corneum, sebum, and hair follicles, resulting in better cure rates and shorter duration of therapy with lower relapse rates.

Uses

Used in Antifungal Treatments:
Terbinafine hydrochloride is used as an antifungal agent for treating various fungal infections, including dermatophyte infections, onychomycosis, and other superficial mycoses. Its fungicidal nature allows for shorter treatment durations and lower relapse rates compared to other oral or topical therapies.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Terbinafine hydrochloride is used as an active ingredient in antifungal medications, such as Lamisil, which are prescribed for the treatment of fungal infections. Its high potency and lipophilic properties make it an effective and popular choice for treating a wide range of fungal infections.
Used in Cosmetic Industry:
Terbinafine hydrochloride can also be used in the cosmetic industry for the development of antifungal products, such as creams, lotions, and shampoos, to treat and prevent fungal infections of the skin, nails, and scalp.
Used in Veterinary Medicine:
In veterinary medicine, Terbinafine hydrochloride is used as an antifungal agent for treating fungal infections in animals, such as dermatophytosis and other superficial mycoses. Its effectiveness and safety make it a valuable treatment option for various animal species.

Originator

Lamisil,Novartis,UK

Indications

Terbinafine (Lamisil) is a second-generation allylamine that is related to naftifine; however, it is 10 to 100 times more potent in vitro. It is fungicidal, whereas griseofulvin, ketoconazole, itraconazole, and other azole derivatives are all fungistatic. Because it is fungicidal, duration of therapy is shorter, and relapse rates are less than with other oral or topical therapies. Terbinafine acts by inhibiting squalene epoxidase and thereby decreasing synthesis of ergosterol, an essential component of fungal cell membranes. It is highly lipophilic and concentrates in the stratum corneum, sebum, and hair follicles. Slightly better cure rates are attained with b.i.d. than with daily dosing.

Therapeutic Function

Antifungal

Synthesis Reference(s)

Tetrahedron Letters, 29, p. 1509, 1988 DOI: 10.1016/S0040-4039(00)80338-X

Antimicrobial activity

Terbinafine is active against a wide range of pathogenic fungi, including dermatophytes (Epidermophyton, Microsporum and Trichophyton spp.), various Candida spp., Aspergillus spp., some dimorphic fungi (Blastomyces dermatitidis, Histoplasma capsulatum and Sporothrix schenckii) and many dematiaceous fungi.

Acquired resistance

Resistance has not been reported.

Pharmaceutical Applications

A synthetic allylamine available as the hydrochloride for oral and topical administration.

Pharmacokinetics

Oral absorption: 70–80% Cmax 250 mg oral: c. 1 mg/L after 2 h Plasma half-life: c. 17 h Volume of distribution: 1000 L Plasma protein binding: >99% Blood concentrations increase in proportion to dosage. It is lipophilic and is rapidly and extensively distributed to body tissues. It reaches the stratum corneum by diffusion through the dermis and epidermis, and secretion in sebum. Diffusion from the nail bed is the major factor in its rapid penetration of nails. It is metabolized by the liver and the inactive metabolites are mostly excreted in the urine. The elimination half-life is prolonged in patients with hepatic or renal impairment.

Clinical Use

Terbinafine hydrochloride can be used in Tinea pedis, tinea corporis, tinea cruris, tinea capitis, Onychomycosis caused by dermatophytes.

Side effects

These include abdominal discomfort, loss of appetite, nausea, diarrhea, headache, impairment of taste, rash and urticaria. Serious skin reactions, including Stevens– Johnson syndrome, and rare hepatotoxic reactions, including jaundice, cholestasis and hepatitis, are occasionally encountered.

Drug interactions

Potentially hazardous interactions with other drugs Antibacterials: concentration reduced by rifampicin.

Metabolism

Terbinafine undergoes extensive first pass loss. It is hepatically metabolised to two major inactive metabolites, 80% of which are renally excreted.

InChI:InChI=1/C21H25N/c1-21(2,3)15-8-5-9-16-22(4)17-19-13-10-12-18-11-6-7-14-20(18)19/h5-7,9-14H,16-17H2,1-4H3/b9-5+

Upstream product

• 14489-75-9 N-methyl-1-naphthalenemethylamine 
• 78629-20-6 3-hydroxy-6,6-dimethylhept-1-ene-4-yne 
• 58064-10-1 tributyl(3,3-dimethyl-1-butyn-1-yl)stannane 
• 116339-41-4 ((E)-3-Iodo-allyl)-methyl-naphthalen-1-ylmethyl-amine 
• 86-52-2 1-Chloromethylnaphthalene 
• 99473-11-7 Demethylterbinafine 
• 74-88-4 methyl iodide 
• 704909-67-1 (Z)-N-(3-chloro-2-propenyl)-N-methyl-1-naphthalenemethanamine 
• 917-92-0 3,3-Dimethylbut-1-yne 
• 134865-58-0 (2E)-3-chloro-N-methyl-N-(naphthalen-1-ylmethyl)prop-2-en-1-amine 
• 32363-94-3 1,1-dichloro-3,3-dimethyl-1-butene 
• 16865-61-5 tert-butyl-2-chloro-acetylene 
• 387383-30-4 N-(3-chloroallyl)-1-methyl-1-naphthylmethylamine 
• 3400-33-7 N-methyl-1-naphthalenecarboxamide 

Downstream Products

• 66-77-3 1-naphthaldehyde 
• 14489-75-9 N-methyl-1-naphthalenemethylamine 
• 138139-82-9 trans-6,6-dimethylhept-2-en-4-yn-1-al 
• 50-00-0 formaldehyd 
• 99473-11-7 Demethylterbinafine 
• 78628-80-5 terbinafine hydrochloride 

Relevant articles and documents

Amine compound as well as preparation method and application thereof

The invention discloses an amine compound containing allyl or benzyl as well as a preparation method and application of the amine compound. The preparation method comprises the steps of sequentially adding a raw material 1, amine, a catalyst and an additive into a reaction solvent, and stirring and reacting for 12-24 hours in an air atmosphere at the temperature of 50-120 DEG C to obtain a reaction solution, wherein the raw material 1 is allyl alcohol or benzyl alcohol, and the molar volume ratio of the raw material 1 to the amine to the catalyst to the additive to the reaction solvent is (0.2 to 8) mmol: (0.4 to 12) mmol: (0.01 to 0.4) mmol: (0.01 to 0.4) mmol: (2 to 40) mL; and removing the reaction solvent of the reaction solution, and then carrying out purification through thin layer chromatography/column chromatography, wherein a developing solvent system is petroleum ether/ethyl acetate, and the amine compound containing allyl or benzyl is obtained. The amine compound can be applied to preparation of framework of biological and pharmaceutical active molecules. The preparation method disclosed by the invention is wide in applicable substrate range, convenient to operate, green and environment-friendly.

Expeditious enyne construction from alkynes via oxidative Pd(II)-catalyzed Heck-type coupling

The enyne, ubiquitous in natural products, can be a challenge to generate since these moieties require many synthetic transformations to assemble them. We developed a simpler protocol to construct enynes while we found that this oxidative reaction was tolerant in substrate scope. In addition, the utility of this reaction was demonstrated through the attempt in synthesizing antifungal agent Lamisil.

IMPROVED PROCESS FOR THE PREPARATION OF TERBINAFINE HYDROCHLORIDE AND NOVEL CRYSTALLINE FORM OF TERBINAFINE

Improved process for the preparation of Terbinafme Hydrochloride compound of formula (I): substantially free of Genotoxic impurity compound of formula (II) and Novel crystalline form of Terbinafine.