Synthetic studies of vitamin D analogs. XXIV. Synthesis of active vitamin D3 analogs substituted at the 2 beta-position and their preventive effects on bone mineral loss in ovariectomized rats.
Analogs related to 1 alpha,25-dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D3 (ED-71) (4), oxa-type and carba-type analogs of vitamin D3 bearing substituents at the 2 beta-position of 1 alpha,25-dihydroxyvitamin D3 (1), were synthesized from the alpha-epoxides (6 and 13). Three analogs, ED-71 (4) and two carba-type analogs (16 and 26), showed potent preventive effects on bone mineral loss in pre-osteoporosis model rats. ED-71 (4) was concluded to be an optimized analog and a promising candidate for the treatment of osteoporosis.
Ono
Y
Y
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Watanabe
H
H
Shiraishi
A
A
Takeda
S
S
Higuchi
Y
Y
Sato
K
K
Tsugawa
N
N
Okano
T
T
Kobayashi
T
T
Kubodera
N
N
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives
D018167:Receptors, Calcitriol; D014807:Vitamin D; D002762:Cholecalciferol; D002117:Calcitriol; C547512:eldecalcitol