GEM-DISPHOPHONIC PRODRUGS OF AMETHOPTERIN (METHOTREXATE) AND DEAZA-N-10 AMETHOPTERIN DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING SUCH PRODUCTS, METHODS OF OBTAINING AND INTERMEDIATE PRODUCTS.

摘要

The synthesis of gem-diphosphonic amethopterin(methotrexate) analogues, and their use as pharmaceutical compositions for various therapeutical applications, are described. In particular, an association of the pro-drug concept with the pharmacological vectorization of antineoplastic agents for bone carcinomata, using diphosphonic acids, is desired. The gem-diphosphonic amethopterin(methotrexate) and 10-N-deaza amethopterin compounds have the form of an amethopterin pro-drug of which the gem-diphosphonic grouping is connected to the pteroylglutamic grouping by a peptide linkage. These compounds are particularly useful in cancerological pharmaceutical compositions particularly intended for treating tumours or metastases, especially those to bone, and/or in rheumatological pharmaceutical compositions particularly intended for treating resistant psoriatic rheumatism, polymyositis, Reiter's disease and rheumatoid arthritis.