SYNTHESIS AND EVALUATION OF (PIPERIDINOMETHYLENE)BIS(PHOSPHONIC ACID)DERIVATIVES AS ANTI-OSTEOPOROSIS AGENTS

Some (piperidinomethylene)bis(phosphonic acid) derivatives were prepar ed and their activity to inhibit a rise in serum calcium induced by pa rathyroid hormone in thyroparathyroidectomised rats was evaluated. Sev eral (4-alkylidene-, 4,4-dialkyl-, or 4-alkyl-4-halopiperidinomethylen e)bis(phosphonic acid) derivatives showed considerable inhibitory acti vity. But compounds having aromatic and polar substituents such as azi do, hydroxy, amino and amido on the piperidine ring were generally ina ctive. 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.