a-HELIX MIMETICS AND METHOD RELATING TO THE TREATMENT OF CANCER STEM CELLS

摘要

The invention provides alpha -mimetic structure of formula (I) wherein A is -(C=O)-CHR₃-, or -(C=O), B is N-R₃- or -CHR₆-, D is -(C=O)-(CHR₇)- or - (C=O) E is -(ZR₈)- or (C=O), G is -(XR₉)n-, -(CHR₁₀)-(NR₆)-, -(C=O)-(XR₁₂)-, -(C=N-W-R₁)-, -(C=O)-, X-(C=O)-R₁₃, X-(C=O)-NR₁₃R₁₄, X-(SO₂)-R₁₃, or X-(C=O)-OR₁₃, W is -Y(C=O)-, -(C=O)NH-, -(SO₂)-, -CHR₁₄, (C=O)-(NR₁₅)-, substituted or unsubstituted oxadiazole, substituted or unsubstituted triazole, substituted or unsubstituted thiadiazole, substituted or unsubstituted 4,5 dihydrooxazole, substituted or unsubstituted 4,5 dihydrothiazole, substituted or unsubstituted 4,5 dihydroimidazole, or nothing, Y is oxygen or sulfur, X and Z is independently nitrogen or CH, n=0 or 1; and R₁ R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉ R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, and R₁₅ are the same or different and independently selected from an amino acid side chain moiety or derivative thereof, the remainder of the molecule, a linker and a solid support, and stereoisomers, salts, and prodrugs thereof, provided that where B is CHR₆ and W is -Y(C=O)-, -(C=O)NH-, -(SO₂), -CHR₁₄, or (C=O)-(NR₁₅)-, G cannot be CHR₉, NR₉, (C=O)-CHR₁₂, (C=O)-NR₁₂, or no atom at all. Additionally, the invention provides methods wherein a-mimetic compounds are used to treat cancer stem cells .