Modulators of the eif2alpha pathway

A method of inhibiting growth of plasmacytoma or increasing protein expression by a cell or in vitro expression system in a patient, said method comprising administering a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, to said patient, wherein said compound has the formula:

• wherein,
• ring A is substituted or unsubstituted cycloalkylene or substituted or unsubstituted arylene;
• L1, L2, L3, and L4 are independently a bond, —NH—, —O—, —S—, —S(O)—, —S(O)2—, substituted or unsubstituted alkylene or substituted or unsubstituted heteroalkylene;
• R1, R3, R5, R6 and R7 are independently hydrogen, halogen, —OCH3, —OCH2Ph, —C(O)Ph, —CH3, —CF3, —CCl3, —CN, —S(O)CH3, —OH, —NH2, —COOH, —CONH2, —NO2, —C(O)CH3, —CH(CH3)2, —CCSi(CH3)3, —C(NN)CF3, —C(NH—NH)CF3, —CCH, —CH2CCH, —SH, —SO2Cl, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC═(O)NHNH2, —NHC═(O)NH2, —NHSO2H, —NHC═(O)H, —NHC(O)OH, —NHOH, —OCH3, —OCF3, —OCHF2, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2 and R4 are independently ═NR7, ═O, or ═S;
• z2 and z4 are independently 0 or 1;
• and
• z5 and z6 are independently an integer from 0 to 5.

A compound, or a pharmaceutically acceptable salt thereof, having the formula:

• wherein,
• ring A is substituted or unsubstituted cycloalkylene or substituted or unsubstituted arylene;
• L1, L2, L3, and L4 are independently a bond, —NH—, —O—, —S—, —S(O)—, —S(O)2—, substituted or unsubstituted alkylene or substituted or unsubstituted heteroalkylene;
• R1, R3, R5, R6 and R7 are independently hydrogen, halogen, —OCH3, —OCH2Ph, —C(O)Ph, —CH3, —CF3, —CCl3, —CN, —S(O)CH3, —OH, —NH2, —COOH, —CONH2, —NO2, —C(O)CH3, —CH(CH3)2, —CCSi(CH3)3, —C(NN)CF3, —C(NH—NH)CF3, —CCH, —CH2CCH, —SH, —SO2Cl, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC═(O)NHNH2, —NHC═(O)NH2, —NHSO2H, —NHC═(O)H, —NHC(O)OH, —NHOH, —OCH3, —OCF3, —OCHF2, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2 and R4 are independently ═NR7, ═O, or ═S;
• z2 and z4 are independently 0 or 1;
• and
• z5 and z6 are independently an integer from 0 to 5;
• with the proviso that the compound is not