摘要

兩個芬布芬類似物4-(biphenyl-4-yl)-N-octyl-4-oxobutanamide、N-(4-(4-(biphenyl-4-yl)-4-oxobutanamido)butyl)-5-(2,5-dimethylphenoxy)-2,2-dimethylpentanamide為一鍋化液相平行合成後篩選之具有癌細胞毒殺潛力藥物。因此透過其放射標幟化合物進行動物造影了解此芬布芬類似物於動物體內之分布情形與相關動力學數據。

錫化前驅物經親電子去金屬化放射性碘標幟製備出放射標幟產物。由商品化4-iodobiphenyl經3步合成錫化前驅物N-octyl-4-oxo-
4-(4'-(trimethylstannyl)biphenyl-4-yl)butanamide (4) 總產率36%、Gemfibrozil經4步合成錫化前驅物5-(2,5-dimethylphenoxy)-2,2-dimethyl-N-(4-(4-oxo-4-(4'-(trimethylstannyl)biphenyl-4-yl)butanamido)butyl)pentanamide (8) 總產率30%。
錫化前驅物(4)經放射化學標幟之產物4-(4'-[123I]iodobiphenyl-4-yl)-N-octyl-4-oxobutanamide (9)放射化學產率9.5%、放射化學純度87%。

Abstract
The two fenbufen analogs 4-(biphenyl-4-yl)-N-octyl-4-
oxobutanamide and N-(4-(4-(biphenyl-4-yl)-4-oxobutanamido)butyl)-5-(2,5-dimethylphenoxy)-2,2-dimethylpentanamide which, were discovered through our combinatorial approach, showed substantial cellular cytotoxicity against cancer cell lines. Thus, we are interested in radiolabeling of these molecules for obtaining the in vivo imaging and the relevant kinetic data. Radioiodinated compounds were prepared through the radioiodination of the required organostannyl precursors.

The first tin precursor N-octyl-4-oxo-4-(4'-(trimethylstannyl)-biphenyl-4-yl)butanamide (4) was prepared from commercial 4-iodobiphenyl via three steps in a total yield of 36%. And second tin precursor 5-(2,5-dimethylphenoxy)-2,2-dimethyl-N-(4-(4-oxo-4-(4'-
(trimethylstannyl)biphenyl-4-yl)butanamido)butyl)pentanamide (8) was prepared from commercial Gemfibrozil via four steps in a total yield of 30%.

Radioiodination of the first tin precursor (4) to 4-(4'-[123I]iodo-biphenyl-4-yl)-N-octyl-4-oxobutanamide (9) was accomplished in a radiochemistry yield of 9.5% and radiochemistry purity of 87%.

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