6173. Mibefradil

Nomenclature

CAS number: 116644-53-2
Methoxyacetic acid (1S,2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl ester; (1S,2S)-2-[2-[[3-(2-benzimidazolyl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl methoxyacetate.
C29H38FN3O3; mol wt 495.63.
C 70.28%, H 7.73%, F 3.83%, N 8.48%, O 9.68%.

Description and references

Selective T-type calcium channel blocker. Prepn: Q. Branca et al., EP 268148; eidem, US 4808605 (1988, 1989 both to Hoffmann-La Roche). Calcium channel selectivity: S. K. Mishra, K. Hermsmeyer, Circ. Res. 75, 144 (1994). Metabolism in rats: H. R. Wiltshire et al., Xenobiotica 22, 837 (1992). Review of pharmacology, toxicology and clinical evaluation: J.-P. Clozel et al., Cardiovasc. Drug Rev. 9, 4-17 (1991); of pharmacology and pharmacokinetics: D. R. Abernethy, Am. J. Cardiol. 80, 4C-11C (1997); of clinical trials in hypertension: S. Oparil, Am. J. Hypertens. 11, 88S-94S (1998); in chronic stable angina pectoris: B. M. Massie, ibid. 95S-102S. Post-marketing safety assessment: J. Riley et al., Int. J. Clin. Pharmacol. Ther. 40, 241 (2002).

Chemical structure

Derivative

Dihydrochloride.

Nomenclature

CAS number: 116666-63-8
Ro-40-5967; Posicor (Roche).
C29H38FN3O3.2HCl.

Properties

Bitter tasting, odorless, white crystalline powder, mp 128°. Chemically stable, light insensitive and water soluble. pKa: 4.8; 5.5. LD50 in mice, rats (mg/kg): 35, 23 i.v.; >800, >800 orally (Clozel).

Therapeutic Category

Antihypertensive.

Keywords

Antihypertensive; Calcium Channel Blocker; Arylalkylamines