New pyridinyl-amino:methylidene bis:phosphonic acid derivs. - used to treat bone disease e.g. osteolytic bone diseases due to malignancy, Paget's disease and osteoporosis

摘要

Pyridinyl-aminomethylidene bisphosphonic acid tetraesters of formula (I) are new: R1-R4 = 1-5C alkyl; X, Y = H, 1-5C alkyl, halo, OH, 1-5C alkoxy, benzyloxy, acyloxy, NO2, CF3 or NR5R6; R5, R6 = H, 1-5C alkyl or acyl. Also claimed is the use of (I) for the treatment of bone diseases, and a pharmaceutical compsn. contg. (I). In an example, 0.2 moles 2-aminopyridine were mixed with 0.8 mol triethylorthoformate and BF3.OEt2 and the mixt.heated at 150[deg]C for 4 hr. and the EtOH formed was distilled off. Triethylorthoformate was distilled off in vacuum. 0.4 mol diethylphosphite was then added to the reaction mixt. which was heated at 150[deg]C while distilling off the EtOH formed. The mixt. was cooled and the prod. purified to give 29g ((2-pyridinylamino) methylidene)bisphosphonic acid tetraethyl ester.