247. Aliskiren

Nomenclature

CAS number: 173334-57-1
(αS,γS,δS,ζS)-δ-Amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-γ-hydroxy-4-methoxy-3-(3-methoxypropoxy)-α,ζ-bis(1-methylethyl)benzeneoctanamide; (2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide; 5S-amino-4S-hydroxy-2S,7S-diisopropyl-8-[4-methoxy-3-(3-methoxypropyloxy)phenyl]octanoic acid N-(2-carbamoyl-2,2-dimethylethyl)amide; CGP-60536.
C30H53N3O6; mol wt 551.76.
C 65.30%, H 9.68%, N 7.62%, O 17.40%.

Description and references

Orally active, synthetic nonpeptide renin inhibitor. Prepn: R. Gschke et al., EP 678503; eidem, US 5559111 (1995, 1996 both to Ciba-Geigy); H, Rüeger et al., Tetrahedron Lett. 41, 10085 (2000). Synthesis: A. Dondoni et al., ibid. 42, 4819 (2001). Determn by HPLC in biological fluids: G. Lefevre, S. Gauron, J. Chromatogr. B 738, 129 (2000); by RIA in plasma: G. Lefevre et al., J. Immunoassay 21, 65 (2000). Structure activity study: J. M. Wood et al., Biochem. Biophys. Res. Commun. 308, 698 (2003). Clinical pharmacology: J. Nussberger et al., Hypertension 39, e1 (2002). Clinical study: A. H. Gradman et al., Circulation 111, 1012 (2005). Review of development and clinical experience: E. O'Brien, Expert Opin. Invest. Drugs 15, 1269-1277 (2006).

Chemical structure

Properties

pKa 9.49. Log P (octanol/water): 2.45 (pH 7.4). Soly in water: >350 mg/ml (pH 7.4).

Derivative

Hemifumarate.

Nomenclature

CAS number: 173334-58-2
CGP-60536B; SPP-100; Rasilez (Novartis).
2C30H53N3O6.C4H4O4; mol wt 1219.59.
C 63.03%, H 9.09%, N 6.89%, O 20.99%.

Therapeutic Category

Antihypertensive.

Keywords

Antihypertensive; Renin Inhibitor