TY - JOUR
T1 - Synthesis of novel progestin-rhenium conjugates as potential ligands for the progesterone receptor
AU - Wüst, F.
AU - Skaddan, M. B.
AU - Leibnitz, P.
AU - Spies, H.
AU - Katzenellenbogen, J. A.
AU - Johannsen, B.
N1 - Funding Information:
Financial support from the Deutsche Forschungsgemeinschaft and Deutscher Akademischer Austauschdienst (to F.W.) and from the US Department of Energy (to J.A.K. and M.B.S.) is gratefully acknowledged. We are grateful to Kathryn E. Carlson for assistance with receptor binding assays.
PY - 1999/9
Y1 - 1999/9
N2 - 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°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.
AB - 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°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.
KW - 21-Substituted progesterone
KW - Progesterone receptor
KW - Relative binding affinities
KW - Rhenium
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U2 - 10.1016/S0968-0896(99)00119-4
DO - 10.1016/S0968-0896(99)00119-4
M3 - Article
C2 - 10530930
AN - SCOPUS:0344994560
SN - 0968-0896
VL - 7
SP - 1827
EP - 1835
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 9
ER -