5583. Losartan

Nomenclature

CAS number: 114798-26-4
2-Butyl-4-chloro-1-[[2′-(2H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol; 2-n-butyl-4-chloro-5-hydroxymethyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole; 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol.
C22H23ClN6O; mol wt 422.91.
C 62.48%, H 5.48%, Cl 8.38%, N 19.87%, O 3.78%.

Description and references

Non-peptide angiotensin II receptor antagonist. Prepn: D. J. Carini, J. J. V. Duncia, EP 253310; D. J. Carini et al, US 5138069 (1988, 1992 both to Du Pont); D. J. Carini et al., J. Med. Chem. 34, 2525 (1991). HPLC determn in plasma: A. Zarghi et al., Arzneim.-Forsch. 55, 569 (2005). Angiotensin receptor binding study: A. T. Chiu et al., J. Pharmacol. Exp. Ther. 252, 711 (1990); receptor subtype specificity: A. T. Chiu et al., Biochem. Biophys. Res. Commun. 172, 1195 (1990). Pharmacology of active metabolite, EXP-3174: P. C. Wong et al., J. Pharmacol. Exp. Ther. 255, 211 (1990). Symposium on pharmacology: Am. J. Hypertens. 4, 271S-353S (1991). Clinical effect on mortality in heart failure: B. Pitt et al., Lancet 355, 1582 (2000). Renoprotective effect in diabetic nephropathy: B. M. Brenner et al., N. Engl. J. Med. 345, 861 (2001). Review of clinical experience in hypertension: M. McIntyre et al., Pharmacol. Ther. 74, 181-194 (1997); of clinical pharmacokinetics: D. A. Sica et al., Clin. Pharmacokinet. 44, 797-814 (2005).

Chemical structure

Properties

Light yellow solid, mp 183.5-184.5°. pKa: 5-6.

Derivative

Monopotassium salt.

Nomenclature

CAS number: 124750-99-8
Du Pont 753; DUP-753; MK-954; Cozaar (DuPont); Lortaan (Merck & Co.); Lorzaar (Merck & Co.); Losaprex (Sigma-Tau); Neo-Lotan (Neopharmed).
C22H22ClKN6O; mol wt 461.00.
C 57.32%, H 4.81%, Cl 7.69%, K 8.48%, N 18.23%, O 3.47%.

Properties

White to off-white free-flowing crystalline powder. Freely sol in water; sol in alcohols; slightly sol in common organic solvents, such as acetonitrile, methy ethyl ketone.

Derivative

Monopotassium salt mixture with hydrochlorothiazide.

Nomenclature

Fortzaar (Merck & Co.); Hyzaar (DuPont).

Therapeutic Category

Antihypertensive.

Keywords

Angiotensin II Receptor Antagonist; Antihypertensive; Biphenyltetrazole Derivatives