Synthetic studies of vitamin D analogs. XXII. Synthesis and antiproliferation activity of putative metabolites of 1 alpha, 25-dihydroxy-22-oxavitamin D3.
As putative metabolites of 1 alpha,25-dihydroxy-22-oxavitamin D3 (OCT), 24-hydroxylated OCT in 24(R) and 24(S) forms, 24-ketoOCT, 26-hydroxylated OCT in 25(S) and 25(R) forms, pentanorOCT and pentanor-ketoOCT were synthesized from the steroidal 20(S)-alcohol. Their antiproliferation activities towards human promyelocytic leukemia cells (HL-60 cells) are also reported. Oxidized derivatives at the C-24 position, 24-ketoOCT, 24(R)-hydroxylated OCT and 24(S)-hydroxylated OCT, showed activities comparable to or slightly weaker than that of OCT, while 26-hydroxylated OCT was less active than OCT. Truncated OCT, pentanor OCT and pentanor-ketoOCT, were inactive at 10(-7)-10(-10) M.
Watanabe
H
H
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Hatakeyama
S
S
Tazumi
K
K
Takano
S
S
Masuda
S
S
Okano
T
T
Kobayashi
T
T
Kubodera
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D018167:Receptors, Calcitriol / Q000378:metabolism
D000970:Antineoplastic Agents; D018167:Receptors, Calcitriol; D002117:Calcitriol; C051883:maxacalcitol