ABSTRACT
The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the composition comprises piperlongumine derivative thereof. The selective killing of senescent cells may delay aging and/or treat age-related disorders.
CLAIMS
1. A compound, the compound of Formula (I):wherein: R is selected from the group consisting of hydrogen, deuterium, halogen, CF3, NO2, and CN; X is selected from the group consisting of CH2, O, NH, S, C(O), and S(O)2; n is an integer from 0-2; A is C(O) or S(O)2; B is selected from the group consisting ofwherein: R1 is selected from the group consisting of hydrogen, deuterium, halogen, CF3, CN, OH, OCH3, OR′, SR′, NR′R′, NR′COR′, NR′CONR′R′, NR′CO2R′, COR′, CO2R′, NOR′, NO2, CONR′R′, OC(O)NR′R′, SO2R′, SO2NR′R′, NR′SO2R′, NR′SO2NR′R′, C(O)C(O)R′, C(O)CH2C(O)R′, a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C1-C6 alkenyl, a substituted or unsubstituted C1-C6 alkynyl, a substituted or unsubstituted aryl, and a substituted or unsubstituted heteroaryl; R′ is independently selected from the group consisting of hydrogen, substituted C1-C4 aliphatic moiety, aliphatic moiety containing nitrogen, oxygen, or sulfur, or alternately, two R′ moieties bound to the same nitrogen atom are optionally taken together with the nitrogen atom to form a 3-7 membered saturated or unsaturated ring having 1-2 additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, or sulfur; C is hydrogen orwherein: R2, R3, R4, R5, and R6 are each independently selected from the group consisting of hydrogen, deuterium, halogen, CF3, CN, OH, OCH3, OR″, SR″, NR″R″, NR″COR″, NR″CONR″R″, NR″CO2R″, COR″, CO2R″, NOR″, NO2, CONR″R″, OC(O)NR″R″, SO2R″, SO2NR″R″, NR″SO2R″, NR″SO2NR″R″, C(O)C(O)R″, and C(O)CH2C(O)R″, a substituted or unsubstituted C1 to C6 alkyl, a substituted or unsubstituted C1 to C6 alkenyl, a substituted or unsubstituted C1 to C6 alkynyl, a substituted or unsubstituted aryl, and a substituted or unsubstituted heteroaryl; R″ is independently selected from the group consisting of hydrogen, substituted C1-C4 aliphatic moiety, aliphatic moiety containing nitrogen, oxygen, or sulfur, or alternately, two R″ moieties bound to the same nitrogen atom are optionally taken together with the nitrogen atom to form a 3-7 membered saturated or unsaturated ring having 1-2 additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, or sulfur; Optionally, R2 and R3, R3 and R4, R4 and R5, and R5 and R6 are taken together to form a 4-8 membered saturated or unsaturated ring having 0-3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, or sulfur; m is an integer from 0-6; and Optionally, the phenyl ring in C or R′ and C taken together may be replaced by the following one or more monocyclic aryl, one or more heteroaryl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from the group consisting of nitrogen, oxygen or sulfur, or an 6-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from the group consisting of nitrogen, oxygen, or sulfur.