Aliskiren

Title: Aliskiren
CAS Registry Number: 173334-57-1
CAS Name: (aS,gS,dS,zS)-d-Amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-g-hydroxy-4-methoxy-3-(3-methoxypropoxy)-a,z-bis(1-methylethyl)benzeneoctanamide
Additional Names: (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
Manufacturers' Codes: CGP-60536
Molecular Formula: C30H53N3O6
Molecular Weight: 551.76
Percent Composition: C 65.30%, H 9.68%, N 7.62%, O 17.40%
Literature References: Orally active, synthetic nonpeptide renin inhibitor. Prepn: R. Göschke 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 therpaeutic potential: K. Allikmets, Curr. Opin. Invest. Drugs 3, 1479-1482 (2002).
Properties: pKa 9.49. Log P (octanol/water): 2.45 (pH 7.4). Soly in water: >350 mg/ml (pH 7.4).
pKa: pKa 9.49
Log P: Log P (octanol/water): 2.45 (pH 7.4)
Derivative Type: Hemifumarate
CAS Registry Number: 173334-58-2
Manufacturers' Codes: CGP-60536B; SPP-100
Trademarks: Rasilez (Novartis)
Molecular Formula: 2C30H53N3O6.C4H4O4
Molecular Weight: 1219.59
Percent Composition: C 63.03%, H 9.09%, N 6.89%, O 20.99%
Therap-Cat: Antihypertensive.
Keywords: Antihypertensive; Renin Inhibitor.
Alitretinoin Alizapride Alizarin Alizarin Cyanine Green F Alizarine Blue

Aliskiren
Aliskiren Structural Formulae V.1.svg
Systematic (IUPAC) name
(2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a607039
Licence data EMA:Link, US FDA:link
Pregnancy cat. C in first trimester
D in second and third trimesters
Legal status POM (UK) -only (US)
Routes PO (oral)
Pharmacokinetic data
Bioavailability Low (approximately 2.5%)
Metabolism Hepatic, CYP3A4-mediated
Half-life 24 hours
Excretion Renal
Identifiers
CAS number 173334-57-1 YesY
ATC code C09XA02
C09XA52 (with HCT)
PubChem CID 5493444
DrugBank DB01258
ChemSpider 4591452 N
UNII 502FWN4Q32 YesY
KEGG D03208 YesY
ChEBI CHEBI:601027 N
ChEMBL CHEMBL1639 N
Chemical data
Formula C30H53N3O6 
Mol. mass 551.758 g/mol
 N (what is this?)  (verify)

Aliskiren (INN) (trade names Tekturna, US; Rasilez, UK and elsewhere) is the first in a class of drugs called direct renin inhibitors. Its current licensed indication is essential (primary) hypertension.

Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[1][2] It was approved by the US Food and Drug Administration in 2007 for the treatment of primary hypertension.[3]

In December 2011, Novartis had to halt a clinical trial of the drug after discovering increased incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension in patients with diabetes and renal impairment (ALTITUDE Trial ).[4] [5]

As a result, in April 20, 2012:

  • A new contraindication was added to the product label concerning the use of aliskiren with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalemia.
  • A warning to avoid use of aliskiren with ARBs or ACEIs was also added for patients with moderate to severe renal impairment (i.e., where glomerular filtration rate is less than 60 ml/min).