Deuterated Cyclosporine Analogs and Methods of Making the Same

摘要

Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabo-lism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and methods of producing immunosuppression with reduced toxicity using the disclosed cyclosporine derivatives.

主权项

1. A cyclosporine A derivative wherein one or more hydrogen atoms in the amino acid position selected from the group consisting of 1, 3 and 9 or combinations thereof are substituted with a deuterium atom and wherein said cyclosporine A derivative is optionally chemically substituted at the amino acid 9 position.