197644-40-9

Upstream product

• 197644-39-6 Oxo-p-tolyl-acetic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 105457-91-8 2-oxo-2-(p-tolyl)acetyl chloride 
• 7163-50-0 (4-methylphenyl)(oxo)acetic acid 
• 5524-56-1 ethyl 2-p-tolyl-2-oxoacetate 
• 197644-43-2 (R)-Hydroxy-phenyl-p-tolyl-acetic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 

Downstream Products

• 197644-41-0 (R)-Hydroxy-(4-hydroxymethyl-phenyl)-phenyl-acetic acid 

Relevant academic research and scientific papers

In vivo muscarinic binding selectivity of (R,S)- and (R,R)-[18F]-fluoromethyl QNB

We have developed a multistep radiochemical synthesis of two diastereomers of quinuclidinyl-4-[18F]-fluoromethyl- benzilate (18F]-FMeQNB), a high-affinity ligand for muscarinic acetylcholine receptors. Previously, we have shown that the nonradioactive (R,R)-diastereomer displays an eightfold selectivity for M1 over M2 while the nonradioactive (R,S)-diastereomer displays a sevenfold selectivity for M2 over M1 in vitro. This paper reports the results of in vivo comparison studies. In the rat, uptake of (R,S)-[18F]-FMeQNB was nearly uniform in all brain regions following the concentration of M2 subtype. The uptake was reduced by 36-54% in all brain regions on coinjection with 50 nmol of unlabeled ligand. An injection of (R,S)-[18F]-FMeQNB followed at 60 min by injection of unlabeled ligand and subsequent sacrifice at 120 min displaced 30-50% of radioactivity in the pens, medulla, and cerebellum, which contain a high proportion of M2 subtype. The most dramatic displacement and inhibition of uptake on coinjection of (R,S)-[18F]-FMeQNB was observed in the heart. In rhesus monkey, the compound showed prolonged uptake and retention in the brain. In the blood, the parent compound degraded rapidly to a single radiolabeled polar metabolite believed to be fluoride. Within 30 min the parent compound represented less than 5% of the plasma activity. Displacement with (R)-QNB was generally slow, but was more rapid from these tissues which contain a higher proportion of M2 subtype. The results are consistent with the hypothesis that (R,S)-[18F]-FMeQNB is M2 selective in vivo. On the other hand, (R,R)-[18F]-FMeQNB showed higher uptake in those brain regions containing a higher concentration of M1 subtype. Uptake in the heart at 60 min was much lower than that observed with the (R,S)-diastereomer. Inhibition of uptake on coinjection with unlabeled (R,S)-FMeQNB is only significant in the heart, thalamus, and pens. Inhibition of uptake on coinjection with unlabeled ((R,S))-FMeQNB is quite uniform in all brain regions. Displacement with (R)-QNB shows a more varying amount displaced. These results are consistent with (RP)-[18F]-FMeQNB being M1 selective in vivo.