Substituted piperazines as disrupters of AB42 oligomer formation

A method for reducing formation of amyloid beta 42 (Aβ42) oligomers or disrupting formation of amyloid beta 42 (Aβ42) oligomers in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula 182:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• (i) R60 is a branched or unbranched (C1-C6) alkyl, wherein the (C1-C6) alkyl is substituted with one aryl substituent and optionally further substituted with one or more substituents independently selected from the group consisting of halogen, C(O)R, C(O)NRR′, C(O)OH, C(O)O (alkyl), NRR′, O(alkyl), O(aryl), saturated cyclic hydrocarbon, unsaturated cyclic hydrocarbon, and aryl;
• or
• (ii) R60 is a branched or unbranched (C1-C6) alkyl, wherein the (C1-C6) alkyl is substituted with one substituent independently selected from the group consisting of C(O)alkyl, C(O)NRR′, C(O)OH, and C(O)O (alkyl), and optionally further substituted with one or more substituents independently selected from the group consisting of halogen, C(O)R, C(O)NRR′, C(O)OH, C(O)O (alkyl), NRR′, OH, O(alkyl), O(aryl), saturated cyclic hydrocarbon, unsaturated cyclic hydrocarbon, and aryl;
• or
• (iii) R60 is a branched or unbranched (C1-C6) alkyl, wherein the (C1-C6) alkyl is substituted with one aryl substituent, one substituent independently selected from the group consisting of C(O)alkyl, C(O)NRR′, C(O)OH, and C(O)O (alkyl), and optionally further substituted with one or more substituents independently selected from the group consisting of halogen, C(O)R, C(O)NRR′, C(O)OH, C(O)O (alkyl), NRR′, OH, O(alkyl), O(aryl), saturated cyclic hydrocarbon, unsaturated cyclic hydrocarbon, and aryl;
• R62 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R63 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R64 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R65 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R66 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R67 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R68 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R69 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R80 is hydrogen, halogen, (C1-C6) alkyl, or O(C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R81 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R82 is OH, O(C1-C6) alkyl, or O(aryl);
• R83 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• R84 is hydrogen, halogen, or (C1-C6) alkyl, wherein the (C1-C6) alkyl is optionally substituted with one or more independently selected substituents;
• each R is independently hydrogen or alkyl, wherein each alkyl is optionally and independently substituted with one or more independently selected substituents;
• each R′ is independently hydrogen or alkyl, wherein each alkyl is optionally and independently substituted with one or more independently selected substituents;
• and
• wherein each optional substituent for each (C1-C6) alkyl of R62, R63, R64, R65, R66, R67, R68, R69, R80, R81, R83, and R84 is independently selected from the group consisting of h alogen, C(O)R, C(O) NRR′, C(O)OH, C(O)O alkyl), NRR′, OH, O(alkyl), OC(O)R, O(aryl), saturated cyclic hydrocarbon, and unsaturated cyclic hydrocarbon.