Synthesis and evaluation of (piperidinomethylene)bis(phosphonic acid) derivatives as anti-osteoporosis agents.
Some (piperidinomethylene)bis(phosphonic acid) derivatives were prepared and their activity to inhibit a rise in serum calcium induced by parathyroid hormone in thyroparathyroidectomised rats was evaluated. Several (4-alkylidene-, 4,4-dialkyl-, or 4-alkyl-4-halopiperidinomethylene)bis(phosphonic acid) derivatives showed considerable inhibitory activity. But compounds having aromatic and polar substituents such as azido, hydroxy, amino and amido on the piperidine ring were generally inactive. In this study, two 4-alkylidene compounds (8a and 8b) and a 4,4-cyclic dialkyl compound (61) showed potent activity when administered either intravenously or perorally.
Mimura
M
M
Central Research Institute, Kaken Pharmaceutical Co., Ltd., Kyoto, Japan.
Hayashida
M
M
Nomiyama
K
K
Ikegami
S
S
Iida
Y
Y
Tamura
M
M
Hiyama
Y
Y
Ohishi
Y
Y
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology*; D010024:Osteoporosis / Q000188:drug therapy*; D016105:Parathyroidectomy; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D063065:Organophosphonates; D010880:Piperidines; D002118:Calcium