Pentapeptide compounds and uses related thereto
View Patent ↗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.