Compounds of reverse turn mimetics and the use thereof
Conformationally constrained compounds that are novel and mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins and having bicyclic framework are disclosed, as well as their prodrugs. Such reverse-turn mimetic structures and prodrugs have utility over a wide range of fields, including use as diagnostic and therapeutic agents. The invention also relates to a use of such compounds for the preparation of a medicament for treating or preventing cancer including an acute myeloid leukemia.
1. A compound having the structure of Formula (III):
wherein:
R 1 is indolyl substituted by C 1-12 alkyl and —COR 12 , wherein R 12 is C 1-12 alkyl;
R 6 is phenyl;
R 4 is allyl;
X 1 is hydrogen; and
each of X 2 and X 3 is independently hydrogen and hydroxyl.
2. A compound having the structure of Formula (IV):
(III)-R 7
wherein (III) is the formula:
R 1 is indolyl substituted by C 1-12 alkyl and —COR 12 , wherein R 12 is C 1-12 alkyl;
R 6 is phenyl;
R 4 is allyl;
X 1 is hydrogen;
each of X 2 and X 3 is independently hydrogen and hydroxyl;
either X 2 or X 3 is linked to R 7 via Y;
Y is an oxygen in X 2 or X 3 ; and
R 7 is hydroxyalkyl, glycosyl, phosphoryloxymethyoxycarbonyl, substituted or unsubstituted piperidine carbonyloxy, or a salt thereof; or Y—R 7 is an amino acid residue, a combination of amino acid residues, phosphate, hemimalate, hemisuccinate, dimethylaminoalkylcarbamate, dimethylaminoacetate, acetate, succinate, malate, formate, benzoate, or a salt thereof.
3. A method for treating an acute myeloid leukemia, comprising administering to a patient in need thereof an effective amount of the compound according to claim 1 .
4. A method for treating an acute myeloid leukemia, comprising administering to a patient in need thereof an effective amount of the compound according to claim 2 .