Synthesis of novel progestin-rhenium conjugates as potential ligands for the progesterone receptor.
To assist in the development of technetium-based radiopharmaceuticals that are useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have synthesized a series of small-sized metal chelates according to 'n + 1' mixed-ligand, thioether-carbonyl and organometallic designs. In these preliminary investigations, rhenium was used as a model for the radioactive technetium. The metal chelates contain the rhenium metal in several oxidation states, being + 5, + 3, and + 1, and they were attached to 21-substituted progesterone derivatives. A competitive receptor-binding assay (rat uterine cytosol, 0 degrees C) was used to determine the binding affinity of these conjugates for the progesterone receptor. The highest affinity of 9% (RU5020 = 100%) was obtained with a '3 + 1' mixed-ligand complex, containing a NMe group as the central donor atom in the tridentate ligand part. This value reflects a relative binding affinity of 75% compared with the parent steroid progesterone.
Wüst
F
F
Institut für Bioanorganische und Radiopharmazeutische Chemie, Dresden, Germany.
Skaddan
M B
MB
Leibnitz
P
P
Spies
H
H
Katzenellenbogen
J A
JA
Johannsen
B
B
D018360:Crystallography, X-Ray; D008024:Ligands; D011372:Progestins / Q000737:chemistry* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism*; D012211:Rhenium / Q000737:chemistry* / Q000378:metabolism; D013057:Spectrum Analysis
D008024:Ligands; D011372:Progestins; D011980:Receptors, Progesterone; D012211:Rhenium