An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines

Abstract

<jats:p>&lt;p&gt;Abstract: Herein, we report further improvements to the synthesis of tenofovir &lt;b&gt;1&lt;/b&gt;, the precursor to tenofovir disoproxil fumarate and tenofovir alafenamide fumarate. Starting from acyclic precursor diaminomalononitrile &lt;b&gt;12&lt;/b&gt;, a four-step protocol to tenofovir &lt;b&gt;1 &lt;/b&gt;will allow for vertical integration for more manufacturers. The key transformation is a more convergent one step procedure from &lt;b&gt;6&lt;/b&gt; as compared to the current commercial process, with an improved yield from 59% (two steps) to 70%. Further improvements include eliminating the need for problematic magnesium &lt;i&gt;tert&lt;/i&gt;-butoxide (MTB) and significant solvent reduction by eliminating the need for an intermediate workup. With the costs of HIV/AIDS treatments remaining a barrier for those most in need, lowering the raw material/processing costs and increasing the security of supply can increase patient access.&lt;/p&gt;</jats:p>

Toward Secure Supply of Remdesivir via a 2-Pot Triazine Synthesis: Supply Centered Synthesis

“…Our prior experience with hydroxypropyl adenine (HPA) suggested that DMF might be a good solvent for the condensation reaction of the amino nitrile with formamidinium acetate. 26 Formamidine acetate was added to the amination reaction mixture and heated to form the triazine with this thought in mind. This provided material in 75% AY over two steps.…”

DFT, molecular docking and ADME prediction of tenofovir drug as a promising therapeutic inhibitor of SARS-CoV-2 Mpro

“…(R)-(((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonic acid known as tenofovir (Fig. 1) is used in the treatment of the HIV and the hepatitis B diseases in combination with other drugs [21][22][23][24]. Tenofovir is accompanied with a very low rate of antiviral resistance and low hepatotoxicity [25][26][27][28].…”