9146. Tenofovir

Nomenclature

CAS number: 147127-20-6
P-[[(1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]phosphonic acid; (R)-9-(2-phosphonomethoxypropyl)adenine; (R)-PMPA; GS-1278.
C9H14N5O4P; mol wt 287.21.
C 37.64%, H 4.91%, N 24.38%, O 22.28%, P 10.78%.

Description and references

Acyclic phosphonate nucleotide analog; reverse transcriptase inhibitor. Prepn: I. Rosenberg et al., Collect. Czech. Chem. Commun. 53, 2753 (1988); A. Holy et al., ibid. 60, 1390 (1995); L. M. Schultze et al., Tetrahedron Lett. 39, 1853 (1998). Prepn of ester prodrug: M. N. Arimilli et al., Antivir. Chem. Chemother. 8, 557 (1997); idem et al., WO 9804569; eidem, US 5922695 (1998, 1999 both to Gilead Sci.). Antiretroviral activity in vitro: J. Balzarini et al., Biochem. Biophys. Res. Commun. 219, 337 (1996). Metabolism and pharmacokinetics of prodrugs: J.-P. Shaw et al., Pharm. Res. 14, 1824 (1997). Clinical trial in HIV-infected patients: J. E. Gallant et al., J. Am. Med. Assoc. 292, 191 (2004). Review of pharmacology and clinical efficacy: P. A. Pham, J. E. Gallant, Expert Opin. Drug Metab. Toxicol. 2, 459-469 (2006).

Chemical structure

Properties

Crystals from boiling water + ethanol, mp 279°. [α]D +21° (c = 1 in 0.1M HCl).

Derivative

Bis(isopropyloxycarbonyloxymethyl) ester.

Nomenclature

CAS number: 201341-05-1
5-[[(1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]-2,4,6,8-tetraoxa-5-phosphanonanedioic acid 1,9-bis(1-methylethyl) ester 5-oxide; tenofovir disoproxil; (R)-bis(POC)PMPA.
C19H30N5O10P; mol wt 519.44.
C 43.93%, H 5.82%, N 13.48%, O 30.80%, P 5.96%.

Properties

Log P (1-octanol/aqueous phosphate buffer): 1.3 (pH 6.5).

Derivative

Disoproxil fumarate.

Nomenclature

CAS number: 202138-50-9
Tenofovir DF; GS-4331-05; Viread (Gilead).
C19H30N5O10P.C4H4O4; mol wt 635.51.
C 43.47%, H 5.39%, N 11.02%, O 35.25%, P 4.87%.

Properties

White to off-white crystalline powder. Log P (octanol/phosphate buffer) at 25°: 1.25 (pH 6.5). Soly in distilled water (25°): 13.4 mg/ml.

Therapeutic Category

Antiretroviral.

Keywords

Reverse Transcriptase Inhibitor; Antiretroviral; Reverse Transcriptase Inhibitors; Nucleosides/Nucleotides