Studies on novel bone resorption inhibitors. I. Synthesis and pharmacological activities of aminomethylenebisphosphonate derivatives.
A series of aminomethylenebisphosphonate derivatives was synthesized and evaluated for their antiresorptive activities using a parathyroid hormone (PTH)-induced hypercalcemia model in rats (PIH model). Among these compounds, (cycloheptylamino)methylenebis(phosphonic acid) (3j) was finally selected for further investigation, proving 10-fold as potent as pamidronate in the PIH model and an immobilization bone atrophy model in rats (DA model). The structure-activity relationships of this series of bisphosphonates are discussed.
Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
M
M
Takeuchi
S
S
Sakamoto
M
M
Yoshida
T
T
Abe
Y
Y
Isomura
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy*; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000627:therapeutic use; D006934:Hypercalcemia / Q000188:drug therapy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D004164:Diphosphonates