Synthesis and Biological Evaluation of 1α,25-Dihydroxyvitamin D3 Analogues with a Long Side Chain at C12 and Short C17 Side Chains

• Published in: Journal of medicinal chemistry Vol. 55; no. 20; pp. 8642 - 8656
• Main Authors: Carballa, Diego M, Seoane, Samuel, Zacconi, Flavia, Pérez, Xenxo, Rumbo, Antonio, Alvarez-Díaz, Silvia, Larriba, María Jesús, Pérez-Fernández, Román, Muñoz, Alberto, Maestro, Miguel, Mouriño, Antonio, Torneiro, Mercedes
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.10.2012
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Cadherins - metabolism; Calcitriol - analogs & derivatives; Calcitriol - chemical synthesis; Calcitriol - pharmacology; Calcium - blood; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cystatins - metabolism; Drug Screening Assays, Antitumor; Female; Humans; Mice; Molecular Docking Simulation; Receptors, Calcitriol - metabolism; Structure-Activity Relationship; Transcription, Genetic - drug effects

Structure-guided optimization was used to design new analogues of 1α,25-dihydroxyvitamin D3 bearing the main side chain at C12 and a shorter second hydroxylated chain at C17. The new compounds 5a–c were efficiently synthesized from ketone 9 (which is readily accessible from the Inhoffen–Lythgoe diol...