DEUTERATED CYCLOSPORIN ANALOG AND USE THEREOF AS IMMUNOMODULATING AGENT

摘要

PROBLEM TO BE SOLVED: To provide a new cyclosporin analog having enhanced efficacy and altered pharmacokinetic and pharmacodynamic parameters.

SOLUTION: The cyclosporin derivative having enhanced effectiveness and reduced toxicity over naturally occurring and other presently known cyclosporin and cyclosporin derivatives is disclosed. The cyclosporin derivative is produced by the following chemical and isotopic substitution of the CsA (cyclosporin A) molecule: (1) chemical substitution and optionally deuterium substitution of an amino acid 1 and (2) deuterium substitution at a key site of metabolism of the cyclosporin A molecule such as amino acids 1, 4 and 9. The most active derivative has both chemical and deuterium substitution. A method for producing the cyclosporin derivative and a method for producing immunosuppression with reduced toxicity using the disclosed cyclosporin derivative are also disclosed.

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