A practical synthesis of the serotonin 5-HT2A receptor antagonist MDL 100907, its enantiomer and their 3-phenolic derivatives as precursors for [11C]labeled PET ligands.
A practical synthesis of the 3-phenolic precursor of MDL 100907, a selective 5-HT2A receptor antagonist, is described. The route was also applied to the enantiomeric series, thus affording the direct precursors of both 3-[11C]MDL 100907 and its enantiomer as ligands for positron emission tomography. Similar methodology was developed for the direct synthesis of MDL 100907 and its enantiomer, MDL 100009. The routes utilized classical optical resolution of the N-nor intermediates in at least 98% enantiomeric excess and easily afforded multigram amounts of the chiral precursors of a variety of N- and 3-O-substituted enantiomers.
Ullrich
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Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0815, USA.
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D002250:Carbon Radioisotopes; D005464:Fluorobenzenes / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D010636:Phenols; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D005464:Fluorobenzenes; D008024:Ligands; D010636:Phenols; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C079049:volinanserin