Synthesis and preliminary biological evaluation of [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate for the fractalkine receptor (CX3CR1)
| Autor: | Mingzhang Gao, Qi Huang Zheng, Jill A. Meyer, Gary D. Hutchins, Jonathan S. Peters, Hamideh Zarrinmayeh, Paul R. Territo, Min Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Stereochemistry Chemistry Organic Chemistry Clinical Biochemistry Radiosynthesis Pharmaceutical Science Total synthesis Methylation Ligand (biochemistry) Biochemistry High-performance liquid chromatography 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Yield (chemistry) Drug Discovery Radioligand Molecular Medicine Specific activity Molecular Biology |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 27:2727-2730 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2017.04.052 |
| Popis: | The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate ([11C]5) was prepared from the acid precursor with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110GBq/μmol with a total synthesis time of ∼40-min from EOB. The radioligand depletion experiment of [11C]5 did not display specific binding to CX3CR1, and the competitive binding assay of ligand 5 found much lower CX3CR1 binding affinity. |
| Databáze: | OpenAIRE |
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