Compounds and methods for blocking apoptosis and inducing autophagy

i) A method of treating a neurodegenerative disease, ischemic brain injury, amyloidosis, inflammatory bowel diseases, liver diseases or a metabolic disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula I, or a compound selected from

• or a pharmaceutically acceptable salt thereof;
• or
• ii) a method of blocking apoptosis and/or inducing autophagy in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula I, or a compound selected from
• or a pharmaceutically acceptable salt thereof;
• or
• iii) an in vitro method of blocking apoptosis and/or inducing autophagy in a cell, comprising contacting the cell with a compound of Formula I, or a compound selected from
• or a pharmaceutically acceptable salt thereof;
• or
• iv) a method of promoting cellular recruitment of TRADD to complex I in a cell, comprising contacting the cell with a compound of Formula I, or a compound selected from
• or a pharmaceutically acceptable salt thereof:
• wherein the compound of Formula I has the following structure:
• wherein
• L is CH2, NR1a, heteroaryl or S(O)n, where n is 0, 1, or 2;
• R1a is independently selected from H, CN, alkyl, and aryl;
• R3 is selected from H, alkyl, and aryl;
• R4 is selected from H, alkyl, and aryl;
• R4′ is selected from H, alkyl, and aryl;
• R5 is selected from H, alkyl, aryl, heteroaryl, —(CH2)pCONR6R7 where p is 0, 1, or 2,
• —CH2NR6R7, —CH(OH)NR6R7, —CH(OH)CH2-cycloalkyl, —CH(OH)CH2-NHcycloalkyl, and —CR10═CHR11;
• R6 is selected from H, alkyl, C3-8cycloalkyl, aryl, and -NHcycloalkyl;
• R7 is selected from H and alkyl;
• or R6 and R7, taken together with the nitrogen atom to which they are attached, form a heterocyclyl;
• R10 is selected from H and halo;
• R11 is cycloalkyl;
• R13 is absent or alkyl, where the alkyl forms an iminium group;
• and
• (a) R1 and R2 are each independently selected from H, CN, alkyl, and aryl;
• or
• (b) R1 and R2, taken together with the atoms to which they are attached, form a heterocyclyl of Formula IA:
• R8 and R8′ are each independently selected from H, alkyl, and aryl;
• or
• (c) R1 and R2, taken together with the atoms to which they are attached, and R3 and R4, taken together with the atoms to which they are attached, form a bicycle of Formula IB:
• R8 and R8′ are each independently selected from H, alkyl, and aryl;
• further wherein when R5 is —(CH2)0CONR6R7, then R7 and R4, taken together with the atoms to which they are attached, may form a heterocyclyl of Formula IC: