859. Atenolol

Nomenclature

CAS number: 29122-68-7
4-[2-Hydroxy-3-[(1-methylethyl)amino]propoxy]benzeneacetamide; 2-[p-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetamide; 1-p-carbamoylmethylphenoxy-3-isopropylamino-2-propanol; ICI-66082; Atehexal (Hexal); Ateno basan (Schoenenberger); Atenol (AstraZeneca); Cuxanorm (TAD); Myocord (Ivax); Prenormine (AstraZeneca); Seles Beta (Schwarz); Tenoblock (Leiras); Tenormin (AstraZeneca); Uniloc (Nycomed).
C14H22N2O3; mol wt 266.34.
C 63.13%, H 8.33%, N 10.52%, O 18.02%.

Description and references

Cardioselective β1-adrenergic blocker. Prepn: Barrett et al., DE 2007751; eidem, US 3663607 and US 3836671 (1970, 1972, 1974 all to I.C.I.). Pharmacology and clinical studies: Giudicelli et al., C. R. Seances Soc. Biol. Ses Fil. 167, 232 (1973); Hansson et al., Acta Med. Scand. 194, 549 (1973); Amery et al., N. Engl. J. Med. 290, 284 (1974). Clinical trial in treatment of alcohol withdrawal syndrome: M. L. Kraus et al., ibid. 313, 905 (1985). HPLC determn of enantiomers in plasma and urine: S. K. Chin et al., J. Chromatogr. 489, 438 (1989). Comprehensive description: V. Caplar et al., Anal. Profiles Drug Subs. 13, 1-25 (1984). Review: J. D. Fitzgerald in Pharmacological and Biochemical Properties of Drug Substances vol. 2, M. E. Goldberg, Ed. (Am. Pharm. Assoc., Washington, DC, 1979) pp 98-147; E. Marmo, Drugs Exp. Clin. Res. 6, 639-663 (1980). Symposium on clinical studies: Drugs 25, Suppl. 2, 1-346 (1983).

Chemical structure

Properties

Crystals from ethyl acetate, mp 146-148°. Also reported as mp 150-152° (Caplar). pKa 9.6. Partition coefficient (n-octanol/phosphate buffer): 0.008 (pH 7.0); 0.052 (pH 8.0). Dipole moment: 5.71 ±0.20 D at 20° in propionic acid. uv max (methanol): 225, 275, 283 nm. Freely sol in methanol; sol in acetic acid, DMSO; sparingly sol in 96% ethanol; slightly sol in water, isopropanol; very slightly sol in acetone, dioxane. Practically insol in acetonitrile, ethylacetate, chloroform. LD50 in mice, rats (mg/kg): 2000, 3000 orally; 98.7, 59.24 i.v. (Fitzgerald).

Therapeutic Category

Antihypertensive, antianginal, antiarrhythmic (class II).

Therapeutic Category (Veterinary)

Antihypertensive; antiarrhythmic (class II).

Keywords

β-Adrenergic Blocker; Antianginal; Antiarrhythmic; Antihypertensive; Aryloxypropanolamine Derivatives