IMPROVED SYNTHESIS OF ZENESULFONAMIDO)-BICYCLO[2.2.1]HEPTYL)HEPT-5-ENOIC ACID (S-145) DERIVATIVES AND THEIR IODINE-125-LABELED RADIOLIGANDSFOR THE STUDY OF THROMBOXANE A(2) RECEPTOR

An improved synthetic scheme for enesulfonamido)-bicyclo[2.2.1]heptyl} -hept-5-enoic acid (S145) and its analogs has been designed. The proce dure involves direct sulfonylation of 2-allyl-3-aminobicyclo[2.2.1]hep tane intermediate followed by ozonolysis and addition of a C5 carboxyl unit. The yield of the final product was significantly improved. (5Z) -7-{3-endo-[(4-iodobenzensulfonamido)-bicyclo [2.2.1]heptyl}hept-5-eno ic acid (HS-145) and )-7-13-endo-[(4-hydroxy-benzensulfonamido)-bicycl o [2.2.1]heptyl] hept-5-enoic acid (HS- 145) were synthesized directly without any protection and deprotection steps. [I-125](5Z)-7-{3-endo- [(4-iodobenzensulfonamido)- bicyclo[2.2.1]heptyl]hept-5-enoic acid ([I -125)HS-145) was prepared from IS-145 through an organotin intermediat e and [I-125]sodium iodide with high specific radioactivity and good r ecovery of radioactivity. [I-125](5Z)-7-{3-endo-[(4-hydroxy zensulfona mido)-bicyclo[2.2.1]-heptyl]hept-5-enoic acid ([I-125]HS-145) was prep ared by direct iodination with sodium iodide using a modified chlorami ne-T method. Both [I-125]HS-145 and [I-125]HS-145 were found to be val uable radioligands for studying thromboxane A2 (TXA2) receptor.