Analogs of dehydrophenylahistins and their therapeutic use

A method of treating myeloma, comprising administering to a subject with myeloma a compound having the structure of Formula II or its tautomers, or pharmaceutically acceptable salts thereof:

• wherein
• R2 and R3 are each separately selected from the group consisting of a hydrogen atom;
• a halogen atom;
• mono-substituted;
• poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
• C1-C12 alkyl, C2-C12 alkenyl, and alkoxy;
• and mono-substituted, poly-substituted or unsubstituted variants of the following residues:
• cycloalkyl, cycloalkoxy, aryl, heteroaryl, amino, and nitro;
• R4 and R6 are each separately selected from the group consisting of hydrogen;
• halogen;
• hydroxyl;
• mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
• C1-C24 alkyl, C2- C24 alkenyl, C2-C24 alkynyl, alkoxy, arylalkyl, heteroarylalkyl, alkyloxycarbonyloxy, alkylcarbonyloxyalkyl, arylcarbonyloxyalkyl, arylalkoxy, alkoxy, and alkylthio;
• mono-substituted, poly-substituted or unsubstituted variants of the following residues:
• aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, cycloalkoxy, aryl, heteroaryl, aryloxy, arylcarbonyl, heterocycloalkyl, amino, aminocarbonyl, amide, aminocarbonyloxy, nitro, azido, phenyl, hydroxyl, thio, alkylthio, arylthio, thiophenyl, carboxy, and cyano;
• X1 and X2 are separately selected from the group consisting of an oxygen atom, a sulfur atom, and a nitrogen atom substituted with a R5 group;
• R5 is selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C1-C12 alkyl, unsaturated C2-C12 alkenyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, and substituted nitro groups;
• Y is selected from the group consisting of an oxygen atom, a sulfur atom, an oxidized sulfur atom, and a nitrogen atom substituted with an R5 group;
• n is 0, 1, 2, 3, or 4;
• and
• Ar is a cyclic or polycyclic aryl or heteroaryl ring system comprising between one and three rings, wherein:
• each ring in said system is separately a 5, 6, 7, or 8 membered ring;
• each ring in said system separately comprises 0, 1, 2, 3, or 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen;
• and
• each ring in said system is optionally substituted with one or more subtituents selected from the group consisting of hydrogen;
• halogen;
• hydroxyl;
• mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
• C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, alkoxy, arylalkyl, heteroarylalkyl, alkyloxycarbonyloxy, alkylcarbonyloxyalkyl, arylcarbonyloxyalkyl, arylalkoxy, alkoxy, and alkylthio;
• mono-substituted, poly-substituted or unsubstituted variants of the following residues:
• aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, cycloalkoxy, aryl, heteroaryl, aryloxy, arylcarbonyl, heterocycloalkyl, amino, aminocarbonyl, amide, aminocarbonyloxy, nitro, azido, phenyl, hydroxyl, thio, alkylthio, arylthio, thiophenyl, carboxy, and cyano;
• and an optionally substituted fused ring selected from the group consisting of dioxole, dithiole, oxathiole, dioxine, dithiine, and oxathiine.