Analogs of dehydrophenylahistins and their therapeutic use
Compounds represented by the following structure (II) are disclosed: as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.
1. A compound having the structure of formula I:
wherein
R 1 , R 4 , and R 6 , are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 24 alkyl, unsaturated C 2 -C 24 alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, azido, substituted nitro, phenyl, and substituted phenyl groups, hydroxy, carboxy, —CO—O—R 7 , cyano, alkylthio, halogenated alkyl including polyhalogenated alkyl, and halogenated carbonyl;
R 1 ′ and R 1 ″ are each independently selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 24 alkyl, unsaturated C 2 -C 24 alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, azido, substituted nitro, phenyl, and substituted phenyl groups, hydroxy, carboxy, —CO—O—R 7 , cyano, alkylthio, halogenated alkyl including polyhalogenated alkyl, and halogenated carbonyl, wherein R 7 is selected from a hydrogen atom, a halogen atom, and saturated C 1 -C 24 alkyl, unsaturated C 2 -C 24 alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, azido, substituted nitro, phenyl, and substituted phenyl groups;
R 2 and R 3 are each hydrogen;
m is an integer equal to zero, one or two;
X 1 and X 2 are oxygen;
Y is oxygen;
Z, for each separate m, if non-zero, and Z 1 , Z 2 , Z 3 and Z 4 are each separately selected from a carbon atom, a sulfur atom, a nitrogen atom or an oxygen atom; and
the dashed bonds may be either single or double bonds, provided that the ring formed by Z m -Z 4 is an aryl or heteroaryl ring.
2. The compound of claim 1 , wherein R 4 is a saturated C 1 -C 24 alkyl or unsaturated C 2 -C 24 alkenyl.
3. The compound of claim 2 , wherein R 4 is tert-butyl.
4. The compound of claim 1 , wherein m is 0.
5. The compound of claim 1 , selected from the group consisting of:
6. A pharmaceutical composition comprising a compound of claim 1 together with a pharmaceutically acceptable carrier.