Synthesis and labelling of epidepride

Synthesis and labelling of epidepride 1 first-author 1 1 1 1 State Key Laboratory of Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 State Key Laboratory of Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 S-(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenzamide (proposed generic name, epidepride) is a very potent dopamine D2 antagonist. It was synthesized by five steps from 3-methoxysalicylic acid. [ 131 I]epidepride was obtained in 97.3% radiochemical yields from the corresponding 5-(tributyltin) derivative using hydrogen peroxide as the oxidant. The aryltin precursor was prepared from non-labelled epidepride by palladium-catalyzed stannylation using bis(tri-n-butyltin) in triethylamine. [ 131 I]epidepride was stable under 4°C, and partition coefficient was 72.3 at pH 7.40. The biodistribution study in rats exihibited high localization in the striatum of the brain with the striatum/cerebellum ratio reaching 237/1 at 320 min postinjection. All these results suggest that [ 131 I]epidepride may be used widely as a useful dopamine D2 receptor imaging agent for SPECT. [ 131 I]epidepride Dopamine D2 antagonist Synthesize Aryltin precursor Biodistribution SPECT References Leslie W D , Abrams D N , Greenberg C R et al . J Nucl Med , 1996 , 37 : 1589 ~ 1591 J Nucl Med Picker W , Riedl M , Luger A et al . J Nucl Med 1996 , 37 : 1931 ~ 1937 J Nucl Med De Herder W W , Reijs A E M , de Swart J et al . Eur J Nucl Med , 1999 , 26 : 46 - 50 Eur J Nucl Med Langer O , Halldin C , Dolle F , et al . Nucl Med Biol , 1999 , 26 : 509 - 518 Nucl Med Biol Bulteau G. France patent 1528014 , 1968 , 4 : 29 Yue E W , Gerdes J M , Mathis C A. J Org Chem , 1991 , 56 : 5451 ~ 5456 J Org Chem Bishop J E , Mathis C A , Gerdes J M et al . J Med Chem , 1991 , 34 ( 5 ): 1612 ~ 1624 J Med Chem Chumpradit S , Kung M P , Billings J et al . J Med Chem , 1993 , 36 ( 2 ): 221 ~ 228 J Med Chem Clanton J A , de Paulis T , Schmidt D E et al . J label Comp Radiopharm , 1991 , 29 : 745 ~ 751 J label Comp Radiopharm Hoberg T , Strom P , Hakan H et al . Helv Chim Acta , 1990 , 73 : 417 ~ 425 Helv Chim Acta O628.5 + 1, O629.7, O621.3 2000-12-07 2001-05-01 2021-02-05 2001 Nuclear Science and Techniques 2 12