Tubulysin and tubulysin agent

摘要

New tubulysin compounds (I) comprise functionally modified derivatives of known tubulysins, i.e. the peptidic thiazole compounds tubulysin A to tubulysin F described in J. Antibiot., 2000, 53, 579-558and . Tubulysin compounds of formula (I) are new. [Image] R : H, alkyl, aryl, OR 1>, NR 1>R 2>or -NH-(CH 2) n-maleimido; n : 2-4; R 1>, R 2>H, alkyl or aryl; U, U' : H, halo, NO 2or NHR 3>; R 3>H, CHO or alkylcarbonyl; T : H or OR 4>; R 4>H, alkyl, aryl, COR 5>, P(O)(OR 6>) 2or SO 3R 6>; R 5>= alkyl, alkenyl, aryl or heteroaryl; R 6>H, alkyl or metal ion; V : H, OR 7>or halo; W : H or alkyl; or V + W : O; R 7>H, alkyl or COR 8>; R 8>alkyl, alkenyl or aryl; X : H, alkyl, alkenyl or CH 2OR 9>; R 9>H, alkyl, alkenyl, aryl or COR 1>0>; Z 1Me or COR 1>1>; R 1>1>alkyl, CF 3or aryl; Y : free electron pair (i.e. is absent), or may also be O if Z = Me. An independent claim is also included for the preparation of (I). ACTIVITY : Cytostatic. MECHANISM OF ACTION : None given in the source material.