Synthesis and in vivo testing of a bromobutyl substituted 1,2-dithia-5,9-diazacycloundecane: a versatile precursor for new 99mTc-bis(aminoethanethiol) complexes.
7-(4'-Bromobutyl)-3,3,11,11-tetramethyl-1,2-dithia-5,9-di azacycloundecane (6) an intermediate for the preparation of new 99mTc-bis(aminoethanethiol) complexes (99mTc-BAT) was synthesized from the corresponding 7-(4'-phenoxybutyl) derivative (5) by ether cleavage with HBr/AcOH. To demonstrate its versatility as an alkylating agent, 6 was reacted with the amines piperidine, morpholine, NH3 and 1-phenyl-1,3,8-triazaspiro(4,5)decan-4-one, yielding the corresponding N-alkylated amines. Mild ring opening affording the BAT-ligands was achieved by reductive cleavage of the disulphide bonds with threo-2,3-dihydroxy-1,4-dimercaptobutane. The 99mTc-BAT complexes prepared by the tin-reduction method proved to be stable under in vitro conditions. With the exception of the 7-(4'-aminobutyl) substituted one, the 99mTc-BAT complexes revealed octanol-buffer partition coefficients (P) of P greater than 1 at physiological pH. The complexes proved to be neutral and the amount of ultrafiltrable 99mTc-BAT complex varied between 8-18%. In contrast to the good in vitro characteristics, the brain uptake values in CD-1 mice were comparably low.
Eisenhut
M
M
Abeilung Nuklearmedizin, Ruprecht-Karls-Universität, Heidelberg, F.R.G.
Brandau
W
W
Missfeldt
M
M
D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D051379:Mice; D011485:Protein Binding; D011877:Radionuclide Imaging; D013440:Sulfides / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D001798:Blood Proteins; D013440:Sulfides; C063042:7-(4'-bromobutyl)-3,3,11,11-tetramethyl-1,2-dithia-5,9-diazacycloundecane