Polyisoprenyl derivatives and uses thereof

A composition for inhibiting neural death, increasing neural activity and/or for reducing one or more negative effects of neurodegeneration comprising a compound of Formula (I) or Formula (H):

• or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient,
• wherein
• R1 is C5-C20 alkyl or C5-C20 alkenyl optionally substituted with 1-3 C6-C20 arylene groups in the chain and that is optionally substituted with 1-3 halo, trifluoromethyl, —OR7, —P(═O)(OR8)(OR9) or —NR10R11 groups;
• R2 is (C5-C20)alkyl or C5-C20 alkenyl optionally substituted with 1-3 C6-C20 aryl groups, which aryl group(s) are optionally substituted with 1-3 halo, trifluoromethyl, —OR7, —P(═O)(OR8)(OR9) or —NR10R11 groups;
• each R3, R4, R5, and R6 is independently OH or C1-C6 alkoxy;
• each R7, R8 and R9 is independently hydrogen, C1-C6 alkyl or C5-C20 aryl;
• and
• each R10 and R11 is independently hydrogen, C1-C6 alkyl or C6-C20 aryl;
• or R10 and R11 together with the nitrogen to which they are attached form a C3-C7 heterocycle;
• wherein each aryl group of R7, R8, R9, R10 and R11 is optionally substituted with 1-3 C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkanoyl, C1-C6 alkanoyloxy, C1-C6 alkoxycarbonyl, halo, cyano, nitro, carboxy, tritluoromethyl, trifluoromethoxy. NR12R13, or S(O)2NR12R13 groups, wherein each R12 and R13 is independently hydrogen or C1-C6 alkyl;
• R14 and R15 are independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C1-C6 alkynyl, optionally substituted C6-C20 aryl, optionally substituted C6-C20 aryl-C1-C6alkyl, optionally substituted heteroaryl and optionally substituted heteroaryl-C1-C6 alkyl, each heteroaryl having 2-14 ring carbon atoms and 1-6 ring heteroatoms selected preferably from N, O, S, and P, wherein each substituted aryl or substituted heteroaryl is independently substituted with 1-3 substituents selected from —OH, halo, C1-C6 alkyl, C1-C6 alkoxy, and —NR10R11 groups;
• or R14 and R15 together with the carbon atom they are attached to form a C3-C7 cycloalkyl ring optionally substituted with 1-3 C1-C6 alkyl groups;
• R16 and R17 independently are hydrogen or C1-C6 alkyl;
• each R18 and R19 are independently selected from the group consisting of a hydrogen, C1-C6 alkyl, and a group of Formula (III):
• wherein R14-R17 and n are as defined as herein;
• Y is —P(═O)(OR18)(OR19) or —CO2R20, wherein R20 is selected from the group consisting of a hydrogen and C1-C6 alkyl;
• Z is
• wherein R21 is hydrogen or C1-C6 alkyl;
• A is C1-C5 alkylene which may have a substituent selected from —OH, halo, C1-C6 alkyl, and C1-C6 alkoxy groups on each carbon;
• r is 0, 1, 2, 3, 4 or 5;
• and
• n is 0, 1, 2, 3, 4 or 5.