Heidelberg Pharma Research Gmbh

Susanne Werner-Simon

Werner Simon

Christian Lutz

Christoph Müller

Torsten Hechler

Michael Kulke

Jan Anderl

Christoph Mueller

Christoph MÜLLER

The present invention relates to novel methods and compounds for synthesizing amanitin derivatives. The invention in particular relates to methods for synthesizing (S)-6-hydroxy-tryptophan derivatives which can be used as building blocks for synthesizing amanitin derivatives or amatoxin drug conjugates. The invention further relates to intermediate compounds of said synthesis pathways for use in amanitin derivative and amatoxin drug conjugate synthesis, and to the use of particular catalysts suited for mediating said synthesis pathways.

Synthesis of (S)-6-hydroxytryptophan and derivatives thereof

The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6'-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Amanitin conjugates

The invention relates to methods for synthesizing amanitin derivatives having an amino group attached to position 6′ of the central tryptophan moiety. The invention furthermore relates to an amanitin derivative having an amino group attached to position 6′ of the central tryptophan moiety, conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

Method of treating cancer using amanitin derivatives

The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4', 5&#x2032; or 7&#x2032; of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.

Method for synthesizing amanitins

The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6' of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6&#x2032; of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

The invention relates to &#x3b3;-amaninamide (1; x=0, 1 or 2), &#x3b3;-amaninamidic acid (2; x=0, 1 or 2), and &#x3b3;-amaninamidic hydroxamic acid (3; x=0, 1 or 2), novel derivatives of &#x3b3;-amanitin (4), and methods and novel building blocks for the synthesis thereof. 

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Ladenburg, Germany

Susanne Werner-Simon