Potent Small Molecule Inhibitors of Autophagy, and Methods of Use Thereof

A compound represented by formula I:

• or a pharmaceutically acceptable salt, biologically active metabolite, solvate, hydrate, prodrug, enantiomer or stereoisomer thereof, wherein
• n is 0, 1, 2, 3 or 4;
• Y is —C(R1)═ or —N═;
• R is —H, lower alkyl, —CH3, lower fluoroalkyl, —CH2F, —CHF2, —CF3, —NO2, —OH, —NH2, —NH(lower alkyl), —N(lower alkyl)2, or lower alkynyl;
• R1 is independently selected for each occurrence from the group consisting of —H, —F, —Cl, —Br, —I, —NO2, —OH, —NH2, —NH(lower alkyl), —N(lower alkyl)2, —CH3, —CF3, —C(═O)(lower alkyl), —CN, —O(lower alkyl), —O(lower fluoroalkyl), —S(═O)(lower alkyl), —S(═O)2(lower alkyl) and —C(═O)O(lower alkyl);
• R2 and R3 are independently selected from the group consisting of —H, lower alkyl, lower fluoroalkyl, lower alkynyl and hydroxyalkyl;
• X is —O—, —S—, —N(H)—, —N(lower alkyl)-, —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2— or —CH2CH2CH2CH2CH2CH2—;
• and
• Z is phenyl, pyridyl, vinyl, morphinyl, phenanthrolinyl, naphthyl, furyl or benzo[d]thiazolyl;
• and optionally substituted with one or more substitutents selected from the group consisting of —CH3, lower alkyl, fluoroalkyl, —OCH3, —OCF3, lower fluoroalkoxy, —F, —Cl, —Br, —I, —NO2, lower alkyoxy, —NH(lower alkyl), —N(lower alkyl)2, —CF3, and 3,4-methylene dioxy;
• provided that the compound is not
• wherein J is Cl, OCHF2, OCH2CH3, OCH2CF3, O(CH2)2CH3, OCH(CH3)2, O(CH2)3CH3, or O(cyclopentyl).