Abstract
The practical synthesis of a mixed phenoxy-amidate derivative of PMPA with high oral bioavailability and favorable pharmacokinetics is described. The non-stereoselective synthetic route produces a 1:1 mixture of two diastereomers at phosphorous. Simulated moving bed chromatography using Chiralpak AS enabled kilo-scale isolation of the more potent diastereomer (GS-7340). The GS-7340 phosphorous chiral center was found to be (S) by X-ray crystallography.
MeSH terms
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Adenine / analogs & derivatives*
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Adenine / chemical synthesis
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Adenine / chemistry*
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Adenine / isolation & purification
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Adenine / pharmacokinetics
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Alanine
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry*
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Anti-HIV Agents / isolation & purification
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Anti-HIV Agents / pharmacokinetics
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Crystallography, X-Ray
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Organophosphonates*
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Organophosphorus Compounds / chemistry*
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Organophosphorus Compounds / pharmacokinetics
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Prodrugs / chemical synthesis
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Prodrugs / chemistry*
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Prodrugs / isolation & purification
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Stereoisomerism
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Tenofovir
Substances
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Anti-HIV Agents
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Organophosphonates
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Organophosphorus Compounds
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Prodrugs
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Tenofovir
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tenofovir alafenamide
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Adenine
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Alanine