83398-52-1

Upstream product

• 70987-78-9 (S)-Glycidyl tosylate 
• 32860-39-2 (2R)-3-fluoropropane-1,2-diol 
• 98-59-9 p-toluenesulfonyl chloride 

Downstream Products

• 146459-59-8 (R)-1-fluoro-2-methoxymethoxypropyl p-toluenesulfonate 
• 146459-57-6 diisopropyl (R)-({[1-fluoro-3-(tosyloxy)propan-2-yl]oxy}methyl)phosphonate 
• 146459-60-1 (R)-2-acetoxymethoxy-3-fluoropropyl p-toluenesulfonate 

Relevant academic research and scientific papers

The Role of Chirality of [18F]SMBT-1 in Imaging of Monoamine Oxidase-B

(S)-(2-Methylpyrid-5-yl)-6-[(3-[18F]fluoro-2-hydroxy)propoxy]quinoline ([18F]SMBT-1) was recently developed as a novel class of selective and reversible monoamine oxidase-B (MAO-B) tracers for in vivo imaging of reactive astrogliosis via positron emission tomography. To investigate the effect of the chirality of [18F]SMBT-1 on tracer performance, we synthesized (S)-[18F]6 ([18F]SMBT-1) and (R)-[18F]6 and compared their binding properties, pharmacokinetics, and metabolism. (S)-6 showed higher binding affinity to MAO-B and lower binding affinity to MAO-A than (R)-6, demonstrating a higher selectivity ratio (MAO-B/MAO-A). A pharmacokinetic study in mice demonstrated that both (S)-[18F]6 and (R)-[18F]6 showed sufficient initial brain uptake. However, (S)-[18F]6 was cleared significantly faster from the body. An abundant sulfoconjugate metabolite M2 was observed in plasma for (S)-[18F]6 but not for (R)-[18F]6. In vitro sulfation assays confirmed that (S)-6 was more reactive than (R)-6, consistent with the in vivo findings. Mefenamic acid, a selective sulfotransferase 1A1 (SULT1A1) inhibitor, strongly inhibited the in vitro sulfation of (S)-6 by mouse liver fractions, human liver cytosol fractions, and human recombinant SULT1A1 enzyme. Genetic polymorphisms of SULT1A1 did not affect the sulfation of (S)-6 in vitro. In conclusion, (S)-[18F]6 had a more favorable binding affinity and binding selectivity for MAO-B than (R)-[18F]6. Additionally, (S)-[18F]6 also possessed better pharmacological and metabolic properties than (R)-[18F]6. These results suggest that (S)-[18F]6 ([18F]SMBT-1) is a promising candidate for application in the imaging of MAO-B in vivo.

SYNTHESIS OF N-(3-FLUORO-2-PHOSPHONOMETHOXYPROPYL) (FPMP) DERIVATIVES OF HETEROCYCLIC BASES

A new groupnof compounds has been prepared: N-(3-fluoro-2-phosphonomethoxypropyl) (FPMP) derivatives of purine and pyrimidine bases which exhibit a significant selective activity against a broad spectrum of retroviruses.Racemic N-(3-fluoro-2-phosphonomethoxypropyl) derivatives of adenine (V), guanine (IX), cytosine (XIII), 2,6-diaminopurine (XXI), 3-deazaadenine (XVII), xanthine (X) and hypoxanthine (VI) were prepared from the corresponding n-(3-fluoro-2-hydroxypropyl) derivatives after protection of amino group at the heterocyclic ring by selective benzoylation, reaction with diisopropyl p-toluenesulfonyloxymethylphosphonate (II), and subsequent removal of the protecting groups.Chiral FPMP derivatives were prepared by reaction of heterocyclic base with corresponding chiral synthon (XXX; XXXVII) followed by deprotection.The required chiral synthons were obtained from enantiomeric 3-fluoro-1,2-propanediols by two methods.In the first, the primary hydroxyl group was tritylated, the obtained derivative was reacted with compound II, the trityl group was removed and the product was mesylated to give synthon XXXVII.The second pathway considered tosylation of the primary hydroxyl group and conversion of the secondary hydroxyl into the acetoxymethyl ether via the methoxymethyl ether; treatment of the acetoxy compound with bromotrimethylsilane and triisopropyl phosphite afforded the desired synthon XXX.