Tubulysin analogues

1. A compound of the following general formula:

wherein:

A represents an optionally substituted 5- or 6-membered heteroaryl ring

X is O, S or a group of Formula NR 13 or CR 14 R 15 ;

Y is O, S or a group of Formula NR 16 and

R 1 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 and R 16 are independently of each other H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl,

R 2 and R 3 together constitute a group of Formula (CH 2 )n wherein n is 4; and

R 8 is hydrogen or alkyl;

R 12 is H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl, heteroaralkyl or NR 18 R 19 ;

R 18 is H or methyl; and

R 19 is aralkyl or heteroaralkyl

or a pharmacologically acceptable salt, solvate, hydrate or a pharmacologically acceptable formulation thereof.

2. A compound of claim 1 , wherein A has the following structure:

3. The compound according to claim 1 wherein R 12 is NR 18 R 19 ;

R 18 is H or methyl;

R 19 has the formula:

wherein:

R 21 is —OH, —NH 2 , alkyloxy, alkylamino or dialkylamino;

R 22 is halogen, —OH, —NO 2 , —NH 2 , alkyloxy, alkylamino or dialkylamino; and

p is 0, 1, 2 or 3.

4. A compound of claim 1 wherein X is a CH 2 group.

5. A compound of claim 1 wherein Y is O.

6. A compound of claim 1 wherein R 1 is C 1 -C 4 alkyl.

7. A compound of claim 1 wherein R 4 is H or methyl.

8. A compound of claim 1 wherein R 5 is H.

9. A compound of claim 1 wherein R 6 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl or C 4 -C 7 alkylcycloalkyl.

10. A compound of claim 1 wherein R 7 is H or methyl.

11. A compound of claim 1 wherein R 9 is C 1 -C 6 alkyl.

12. A compound of claim 1 wherein R 10 is H or methyl.

13. A compound of claim 1 wherein R 11 is H or a group of Formula (C═O)—(C 1-4 )alkyl.

14. A compound of claim 1 wherein R 12 is a group of Formula NR 18 R 19 , wherein R 18 is H or methyl and R 19 is aralkyl or heteroaralkyl.

15. A pharmaceutical composition comprising a compound of claim 1 and optionally one or more carriers and/or adjuvants.

16. A method for treating a patient suffering from colon adenocarcinoma, breast adenocarcinoma, ovarian adenocarcinoma, epidermoid adenocarcinoma or prostate adenocarcinoma, comprising administering to the patient one or more compounds of claim 1 .

17. The method of claim 16 wherein the patient is identified as suffering from colon adenocarcinoma, breast adenocarcinoma, ovarian adenocarcinoma, epidermoid adenocarcinoma or prostate adenocarcinoma, and the one or more compounds are administered to the identified patient.