Synthesis and evaluation of a 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71).
A 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71, 2), 3-epi-ED-71 (4), was synthesized by the convergent method coupling the A-ring fragment (5) with the C/D-ring fragment (6). As the results of preliminary in vitro biological evaluation of 3-epi-ED-71 (4), the inhibition of parathyroid hormone secretion in bovine parathyroid cells and binding affinity to human recombinant vitamin D receptor and to human vitamin D binding protein in comparison with ED-71 (2), 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, 1), and 3-epi-1,25(OH)2D3 (3) are described.
Hatakeyama
Susumi
S
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
Nagashima
Satoshi
S
Imai
Naoko
N
Takahashi
Keisuke
K
Ishihara
Jun
J
Sugita
Atsuko
A
Nihei
Takeshi
T
Saito
Hitoshi
H
Takahashi
Fumiaki
F
Kubodera
Noboru
N
D000818:Animals; D002417:Cattle; D002762:Cholecalciferol / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000166:cytology; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D002762:Cholecalciferol