New C15-Substituted Active Vitamin D3

• Published in: Organic letters Vol. 13; no. 11; pp. 2852 - 2855
• Main Authors: Shindo, Kanako, Kumagai, Go, Takano, Masashi, Sawada, Daisuke, Saito, Nozomi, Saito, Hiroshi, Kakuda, Shinji, Takagi, Ken-ichiro, Ochiai, Eiji, Horie, Kyohei, Takimoto-Kamimura, Midori, Ishizuka, Seiichi, Takenouchi, Kazuya, Kittaka, Atsushi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03.06.2011
• Subjects: Calcitriol - analogs & derivatives; Calcitriol - chemical synthesis; Calcitriol - chemistry; Calcitriol - metabolism; Crystallography, X-Ray; Humans; Molecular Conformation; Molecular Structure; Receptors, Calcitriol - metabolism
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol200828s

C15-Substituted 1α,25-dihydroxyvitamin D3 analogs were synthesized for the first time to investigate the effects of the modified CD-ring on biological activity concerning the agonistic positioning of helix-3 and helix-12 of the vitamin D receptor (VDR). X-ray cocrystallographic analysis proved that 0.6 Å shifts of the CD-ring and shrinking of the side chain were necessary to maintain the position of the 25-hydroxy group for proper interaction with helix-12. The 15-hydroxy-16-ene derivative showed higher binding affinity for hVDR than the natural hormone.