US 11,702,451 B2
Method for synthesizing amanitins
Christian Lutz, Ladenburg (DE); Werner Simon, Ladenburg (DE); Susanne Werner-Simon, Ladenburg (DE); Christoph Müller, Ladenburg (DE); Torsten Hechler, Ladenburg (DE); and Michael Kulke, Ladenburg (DE)
Assigned to Heidelberg Pharma Research GmbH, Ladenburg (DE)
Filed by Heidelberg Pharma Research GmbH, Ladenburg (DE)
Filed on Jan. 13, 2021, as Appl. No. 17/147,569.
Application 17/147,569 is a division of application No. 16/637,376, granted, now 10,961,277, previously published as PCT/EP2018/071268, filed on Aug. 6, 2018.
Claims priority of application No. 17185182 (EP), filed on Aug. 7, 2017.
Prior Publication US 2021/0130412 A1, May 6, 2021
Int. Cl. C07K 7/64 (2006.01); A61K 47/68 (2017.01); A61K 38/00 (2006.01)
CPC C07K 7/64 (2013.01) [A61K 47/6831 (2017.08); A61K 38/00 (2013.01)] 20 Claims
 
1. An amanitin derivative comprising a hydroxylated tryptophan moiety, which is selected from (i) S-desoxy-4′-hydroxy-amanin, 4′-hydroxy-amanin, S-desoxy-5′-hydroxy-amanin, 5′-hydroxy-amanin, S-desoxy-7′-hydroxy-amanin, 7′-hydroxy-amanin, (ii) S-desoxy-4′-hydroxy-amaninamide, 4′-hydroxy-amaninamide, S-desoxy-5′-hydroxy-amaninamide, 5′-hydroxy-amaninamide, S-desoxy-7′-hydroxy-amaninamide, and 7′-hydroxy-amaninamide, and (iii) a derivative of the amanitin according to (i), wherein the free carboxylic acid moiety of amino acid 1 is converted to a carboxylic ester —C(═O)OR1 or to a moiety —C(═O)NH—OR1, wherein R1 is selected from alkyl, aryl, heteroaryl, substituted alkyl, substituted aryl, and substituted heteroaryl, and wherein amino acid 1 is positioned between the cysteinyl residue and the hydroxy-prolyl residue of the amanitin derivative.