6432. Nebivolol

Nomenclature

CAS number: 118457-14-0; 99200-09-6 (unspecified stereo)
(αR,α′R,2R,2′S)-rel-α,α′-[Iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol]; α,α′-(iminodimethylene)bis[6-fluoro-2-chromanmethanol]; dl-nebivolol; narbivolol; R-65824.
C22H25F2NO4; mol wt 405.44.
C 65.17%, H 6.22%, F 9.37%, N 3.45%, O 15.78%.

Description and references

β1-Adrenergic blocker; nitric oxide-mediated vasodilator. Prepd as racemic mixture of (R,S,S,S)- and (S,R,R,R)-enantiomers. Prepn: G. R. E. Van Lommen et al., EP 145067; eidem, US 4654362 (1985, 1987 both to Janssen); eidem, J. Pharm. Belg. 45, 355 (1990). HPLC fluorescence determn in plasma: R. Woestenborghs et al., Methodol. Surv. Biochem. Anal. 18, 215 (1988). Receptor binding study: P. J. Pauwels et al., Mol. Pharmacol. 34, 843 (1988). Clinical study of vasodilating effects: J. R. Cockcroft et al., J. Pharmacol. Exp. Ther. 274, 1067 (1995). Clinical trial in hypertension: T. J. Cleophas et al., Clin. Ther. Res. 62, 451 (2001); in endothelial dysfunction with hypertension: N. Tzemos et al., Circulation 104, 511 (2001). Review of pharmacology: M. Mangrella et al., Pharmacol. Res. 38, 419-431 (1998); of clinical development: J. Cockcroft, Expert Opin. Pharmacother. 5, 893-899 (2004).

Chemical structure

Derivative

Hydrochloride.

Nomenclature

CAS number: 152520-56-4
R-67555; Bystolic (Forest); Lobivon (Menarini); Nebilet (Menarini); Nebilox (GSK).
C22H25F2NO4.HCl; mol wt 441.90.
C 59.80%, H 5.93%, F 8.60%, N 3.17%, O 14.48%, Cl 8.02%.

Properties

White to almost white powder. Sol in methanol, dimethylsulfoxide, N,N-dimethylformamide; sparingly sol in ethanol, propylene glycol, polyethylene glycol; very slightly sol in hexane, dichloromethane, methylbenzene.

Therapeutic Category

Antihypertensive.

Keywords

β-Adrenergic Blocker; Antihypertensive; Aryloxypropanolamine Derivatives; Vasodilator (Peripheral)