Synthesis of novel progestin-rhenium conjugates as potential ligands for the progesterone receptor

• Published in: Bioorganic & medicinal chemistry 1999-09, Vol.7 (9), p.1827-1835
• Main Authors: WÜST, F, SKADDAN, M. B, LEIBNITZ, P, SPIES, H, KATZENELLENBOGEN, J. A, JOHANNSEN, B
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Crystallography, X-Ray; Hormones. Endocrine system; Ligands; Medical sciences; Pharmacology. Drug treatments; Progestins - chemistry; Progestins - metabolism; Receptors, Progesterone - metabolism; Rhenium - chemistry; Rhenium - metabolism; Spectrum Analysis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(99)00119-4

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.