Tenofovir
[CAS 147127-20-6]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antiviral drugs
• Name: Tenofovir
• Synonyms: 1-(6-Aminopurin-9-yl)propan-2-yloxymethylphosphonic acid
• Molecular Formula: C₉H₁₄N₅O₄P
• Molecular Weight: 287.22
• CAS Registry Number: 147127-20-6
• EC Number: 604-571-2
• SMILES: C[C@H](CN1C=NC2=C(N=CN=C21)N)OCP(=O)(O)O

Properties

• Density: 1.8±0.1 g/cm³ Calc.^*
• Melting point: 276-280 °C (Expl.)
• Boiling point: 616.1±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 326.4±34.3 °C (Calc.)^*
• Solubility: water: 13.4 mg/mL (25 °C), DMSO: 4 mg/mL, Ethanol: <1 mg/mL (Expl.)
• Index of refraction: 1.74 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05 Danger
• Risk Statements: H318
• Safety Statements: P264+P265-P280-P305+P354+P338-P317

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Serious eye damage	Eye Dam.	1	H318

chemBlink Chemical Story

Tenofovir, CAS 147127-20-6, is the anhydrous form of the acyclic nucleotide analogue also known as (R)-PMPA. PubChem identifies it as a phosphonic acid derivative and an inhibitor of HIV-1 reverse transcriptase. Its history belongs to the development of acyclic nucleoside phosphonates associated especially with the work of Antonín Holý and Erik De Clercq, whose collaboration established this unusual class of antiviral chemistry.

The molecule resembles a nucleotide closely enough to enter antiviral biochemical pathways, but it replaces the normal sugar-phosphate architecture with a chemically stable phosphonomethoxypropyl side chain attached to adenine. Inside cells, tenofovir is converted to tenofovir diphosphate. This active metabolite competes with the natural nucleotide substrate used by viral reverse transcriptase and, after incorporation, prevents normal extension of viral DNA.

A major medicinal-chemistry challenge is the phosphonate group itself. At physiological pH it is strongly ionized, which is valuable for the active nucleotide mimic but poor for passive passage through biological membranes. Tenofovir therefore became clinically practical through prodrug design. Tenofovir disoproxil fumarate masks the phosphonate with ester groups that improve oral delivery; tenofovir alafenamide is a later prodrug designed to deliver the active compound more efficiently to target cells. The parent tenofovir molecule and its prodrugs must therefore be distinguished when discussing formulation, dose or pharmacokinetics.

Tenofovir-based medicines became central components of combination antiretroviral therapy for HIV and are also used against hepatitis B virus. The parent compound's chemical story is consequently not simply one of discovering an antiviral molecule. It is also a story of solving a delivery problem created by the very phosphonate group required for antiviral action.

The distinction between CAS forms matters as well. CAS 147127-20-6 denotes anhydrous tenofovir, whereas CAS 206184-49-8 in this batch denotes the monohydrate. Hydration changes crystal composition and solid-state properties but not the identity of the pharmacologically relevant tenofovir framework.

References:
1. PubChem, Tenofovir, CID 464205, CAS 147127-20-6.
2. De Clercq E, Holý A et al. Nature. 1986;323:464-467.
3. De Clercq E. Antiviral activity spectrum and target of action of different classes of nucleoside analogues. Nucleosides Nucleotides. 1994;13:1271-1295.
4. U.S. NIH LiverTox, Tenofovir, updated 2020.

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