9156. Terbinafine

Nomenclature

CAS number: 91161-71-6
N-[(2E)-6,6-Dimethyl-2-hepten-4-yn-1-yl]-N-methyl-1-naphthalenemethanamine; trans-N-methyl-N-(1-naphthylmethyl)-6,6-dimethylhept-2-en-4-ynyl-1-amine.
C21H25N; mol wt 291.43.
C 86.55%, H 8.65%, N 4.81%.

Description and references

Orally active, antimycotic allylamine related to naftifine, q.v. Specific inhibitor of squalene epoxidase, a key enzyme in fungal ergosterol biosynthesis. Prepn: A. Stütz, EP 24587; idem, US 4755534 (1981, 1988 both to Sandoz); A. Stütz, G. Petranyi, J. Med. Chem. 27, 1539 (1984). Mode of action: G. Petranyi et al., Science 224, 1239 (1984); N. S. Ryder, Antimicrob. Agents Chemother. 27, 252 (1985). In vitro antifungal activity: S. Shadomy et al., Sabouraudia 23, 125 (1985). CE determn in pharmaceutical formulations: P. Mikus et al., Talanta 65, 1031 (2005). Symposium on pharmacology and clinical trials: J. Am. Acad. Dermatol. 23, Suppl., 775-812 (1990). Clinical trial as systemic treatment of toenail onychomycosis: E. G. V. Evans et al., Br. Med. J. 318, 1031 (1999); A. Tavkkol et al., Am. J. Geriatr. Pharmacother. 4, 1 (2006).

Chemical structure

Derivative

Hydrochloride.

Nomenclature

CAS number: 78628-80-5
SF-86-327; Lamisil (Novartis).
C21H25N.HCl; mol wt 327.89.
C 76.92%, H 7.99%, N 4.27%, Cl 10.81%.

Properties

Crystals from 2-propanol + diethyl ether, mp 195-198° (change in crystal structure begins ≈150°). Freely sol in methanol, methylene chloride; sol in ethanol; slightly sol in water. LD50 in mice, rats (mg/kg): 4000, 4000 orally; 393, 213 i.v. See: U. Ganzinger et al., Proc. 13th Int. Congr. Chemother. 6, 116/52 (1983).

Therapeutic Category

Antifungal.

Therapeutic Category (Veterinary)

Antifungal.

Keywords

Antifungal (Synthetic); Allylamines