Bisphosphonates are a class of drugs which show a broad spectrum of biological activity. The main clinical application of bisphosphonates is connected with diseases characterized by calcium metabolism disorder, like osteoporosis, Paget`s disease or hypercalcemia. Bisphosphonates are also used to prevent skeletal fractures and as auxiliary therapy in case of bone metastases of some cancer.

In literature, about 10.000 bisphosphonic acids are described and most of them are hydroxybisphosphonic acids. From all bisphosphonates present on the drug list only one is a aminomethylidenebisphosphonic acid - Incadronate (cycloheptylamino- methylidenebis-phosphonic acid). The most often used method for preparation of this group of bisphosphonic acids relays on the reaction of trialkyl orthoformate, primary or secondary amine and dialkyl phosphonate. The crude reaction mixture is hydrolyzed and the free acid is separated. This reaction has a few disadvantages: reaction yield that rarely exceeds 30-50%, harsh reaction conditions and formation a number of a sideproducts which hinder separation of the main product.

We recently developed a new method of synthesis of the aminomethylidenebisphosphonic acids. It is based on the reaction of isocyanide with trialkyl phosphite in the presence of stoichiometric amount of hydrochloride. This reaction occur at mild conditions and gives a high yield. As a result, a series of aromatic bis(aminomethylidenebisphosphonic) acids were obtained. Their anti-proliferative activity towards MCF-7 human breast cancer cells, HL-60 human promyelocytic leukemia cells and J774E mouse macrophages were evaluated. Some of them shown promising activity comparable with commercially available zoledronic acid.

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