Deuterated cyclosporine analogs and their use as...

Details Deuterated cyclosporine analogs and their use as... Deuterated cyclosporine analogs and their use as...

A - Human Necessities

61

K

A61K 38/13 (2006.01) A61K 38/12 (2006.01) A61P 37/06 (2006.01) C07B 59/00 (2006.01) C07K 7/64 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2372639

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 metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. The most active derivatives of the invention were those possessing both chemical and deuterium substitution. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

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