Pentapeptide compounds and uses related thereto
Pentapeptide compounds are disclosed. The compounds have biological activity, e.g., cytotoxicity. Prodrugs having targeting groups and pentapeptide moieities, as well as precursors thereof are also disclosed. For example, precursors having a reactive linker that can serve as a reaction site for joining to a targeting agent, e.g., an antibody, as disclosed.
1. A compound of the formula:
and pharmaceutically acceptable salts and solvates thereof,
wherein, independently at each location:
R 1 is selected from hydrogen and lower alkyl;
R 2 is selected from hydrogen and lower alkyl;
R 3 is lower alkyl;
R 4 is selected from lower alkyl, aryl, and —CH 2 —C 5-7 carbocycle when R 5 is selected from H and methyl, or R 4 and R 5 together form a carbocycle of the partial formula —(CR a R b ) n — wherein R a and R b are independently selected from hydrogen and lower alkyl and n is selected from 2, 3, 4, 5 and 6;
R 6 is selected from hydrogen and lower alkyl;
R 7 is sec-butyl or iso-butyl;
R 8 is selected from hydrogen and lower alkyl;
R 9 is selected from
R 10 is selected from
R 11 is selected from hydrogen and lower alkyl;
R 12 is selected from lower alkyl, halogen, and methoxy, and m is 0–5 where R 12 is independently selected at each occurrence;
R 14 is selected from a direct bond, arylene (lower alkylene), lower alkylene and arylene; and
R 15 is selected from hydrogen, lower alkyl and aryl.
2. The compound of claim 1 wherein R 10 is
3. The compound of claim 1 wherein R 10 is
4. The compound of claim 1 having the structure
5. The compound of claim 1 having the structure
6. The compound of claim 1 having the structure
wherein R 4 is iso-propyl or sec-butyl and R 5 is hydrogen.