Tenofovir, 泰诺福韦

Tenofovir is an acyclic nucleoside phosphonate that exhibits anti-viral properties through its inhibition of reverse transcriptases. In particular, Tenofovir is a potent inhibitor of Human Immunodeficiency Virus (HIV) and chronic Hepatitis B Virus (HBV) reverse transcriptases, thus preventing the replication of genetic viral material. This property is beneficial in virus research areas and developing antiviral treatments. Once inside the body tenofovir is metabolized into its active form, tenofovir diphosphate, by the lysosomal protease cathepsin A, nucleotide kinases and adenylate kinases. An oral prodrug, used in the treatment of HIV, is tenofovir alafenamide (TAF) hemifumerate and this has improved stability, greater antiviral activity and reduces the risk of side effects such as loss of kidney function. Furthermore, TAF is easily metabolized into tenofovir in the lymphocytes allowing increased drug accumulation in HIV cells.

Tenofovir is a nucleotide reverse transcriptase inhibitor that is used to treat viral infections, including HIV. The drug was first approved by the U.S. Food and Drug Administration (FDA) in 2001 and has since become one of the most widely prescribed antiretroviral drugs in the world. Tenofovir is sold under various brand names, including Viread, Vemlidy, Tenvir, and others.

Physical and Chemical Properties

Tenofovir is a white to off-white crystalline powder that is freely soluble in water. The drug has a molecular formula of C9H14N5O4P and a molecular weight of 287.21 g/mol. Tenofovir has a melting point of 234-238°C and a log P of -1.5.

Synthesis and Characterization

Tenofovir can be synthesized through a multi-step process that involves the conversion of adenine into the corresponding phosphoramidate, which is then coupled with a modified form of isopropyl alcohol. The resulting ester is then deprotected to generate tenofovir.

The purity and identity of tenofovir can be characterized through various analytical techniques, including high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS).

Analytical Methods

HPLC is a commonly used technique for the quantitative determination of tenofovir in various biological matrices, including plasma, urine, and cerebrospinal fluid. The method involves the separation of tenofovir from other components in the sample using a chromatographic column and the detection of the drug using a UV detector.

NMR spectroscopy can be used to characterize the structure and purity of tenofovir. The technique involves the application of a strong magnetic field to the sample, which causes the nuclei of the atoms to align with the field. The signals generated by the aligned nuclei can be used to identify the molecular structure of the compound.

MS is a powerful technique for the identification and quantification of small molecules, such as tenofovir. The method involves the ionization of the sample and the separation of the resulting ions based on their mass-to-charge ratio.

Biological Properties

Tenofovir is a highly effective inhibitor of reverse transcriptase, an enzyme that is essential for the replication of HIV. The drug is also active against other viruses, including hepatitis B virus (HBV) and herpes simplex virus (HSV).

Tenofovir has a long half-life, which allows for once-daily dosing. The drug is well-tolerated by most patients and has a low incidence of side effects.

Toxicity and Safety in Scientific Experiments

In preclinical studies, tenofovir has been shown to be generally safe and well-tolerated in animals. The drug has a low acute toxicity and does not produce significant adverse effects at therapeutic doses.

Applications in Scientific Experiments

Tenofovir is used extensively in scientific research to study the mechanism of HIV replication and to develop new antiretroviral drugs. The drug is also used to investigate the pathogenesis of other viral infections, including HBV and HSV.

Current State of Research

Tenofovir continues to be an important drug in the treatment of HIV and other viral infections. Ongoing research is focused on developing new formulations of tenofovir that can be administered in novel ways, such as through the skin or intravaginally, to improve adherence and increase efficacy.

Potential Implications in Various Fields of Research and Industry

Tenofovir has potential applications in a variety of fields, including drug delivery, nanotechnology, and biotechnology. The drug can be incorporated into nanoparticles and other delivery systems to improve the targeting and efficacy of antiviral therapies.

Limitations and Future Directions

Despite its effectiveness, tenofovir has a number of limitations, including the development of drug resistance and the potential for renal toxicity. Future research will focus on developing new antiretroviral drugs that are less prone to resistance and toxicity, and on improving the efficacy and safety of existing drugs.

List of Future Directions:

- Development of tenofovir-based combination therapies for HIV and other viral infections

- Evaluation of tenofovir in the prevention and treatment of other viral diseases, such as respiratory viral infections and hepatitis C

- Study of the long-term safety and efficacy of tenofovir in children and adolescents

- Development of novel formulations of tenofovir for improved drug delivery and adherence

- Investigation of the potential of tenofovir-based nanoparticles in improving the efficacy of antiviral therapies

- Exploration of the use of tenofovir in combination with other drugs for the treatment of drug-resistant viral infections

- Investigation of the pharmacokinetics and pharmacodynamics of tenofovir in different patient populations, such as pregnant women

- Development of strategies to minimize the risk of tenofovir-induced renal toxicity

- Exploration of the use of tenofovir in the prevention of HIV transmission in high-risk populations

- Investigation of the effect of tenofovir on the immune system and its potential applications in immunotherapy.

Title: Tenofovir

CAS Registry Number: 147127-20-6

CAS Name: [[(1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]phosphonic acid

Additional Names: (R)-9-(2-phosphonomethoxypropyl)adenine; (R)-PMPA

Manufacturers' Codes: GS-1278

Molecular Formula: C9H14N5O4P

Molecular Weight: 287.21

Percent Composition: C 37.64%, H 4.91%, N 24.38%, O 22.28%, P 10.78%

Literature 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., Antiviral 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).

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

Melting point: mp 279°

Optical Rotation: [a]D +21° (c = 1 in 0.1M HCl)

Derivative Type: Bis(isopropyloxycarbonyloxymethyl) ester

CAS Registry Number: 201341-05-1

CAS Name: 5-[[(1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]-2,4,6,8-tetraoxa-5-phosphanononanedioic acid bis(1-methylethyl) ester 5-oxide

Additional Names: tenofovir disoproxil; (R)-bis(POC)PMPA

Molecular Formula: C19H30N5O10P

Molecular Weight: 519.44

Percent Composition: C 43.93%, H 5.82%, N 13.48%, O 30.80%, P 5.96%

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

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

Derivative Type: Disoproxil fumarate

CAS Registry Number: 202138-50-9

Additional Names: Tenofovir DF

Manufacturers' Codes: GS-4331-05

Trademarks: Viread (Gilead)

Molecular Formula: C19H30N5O10P.C4H4O4

Molecular Weight: 635.51

Percent Composition: C 43.47%, H 5.39%, N 11.02%, O 35.25%, P 4.87%

Properties: White, fine, powder-like crystals.

Therap-Cat: Antiviral.

Keywords: Reverse Transcriptase Inhibitor; Antiviral; Purines/Pyrimidinones.