CONJUGATES OF HUPERZINE AND ANALOGS THEREOF

摘要

Compounds and compositions for treating neurodegenerative diseases are described. The compounds include a therapeutic agent covalently linked with huperzine or an analog thereof through a linker. Methods of preparing the compounds are described. Methods of treating a neurodegenerative disease by administering compounds and compositions including a therapeutic agent covalently linked with huperzine or an analog thereof are described. Methods for delivering a therapeutic agent by administering the therapeutic agent covalently linked to huperzine or an analog thereof are described.

主权项

1. A compound having a general formula: tautomer thereof, or pharmaceutically acceptable salt thereof, wherein R1 is selected from —H, —(C1-C24)alkyl, —CF3, —CF2CF3, —CF2CF2CF3, —SO2CH3, —SO2Ph, —SO2Ar, —SO3H, and —SO3Ar, and —CH2-L-T; R2 is selected from —H, —(C1-C24)alkyl, -aryl, -cycloalkyl, —(C2-C24)alkenyl, -heterocycle, -heteroaryl, and —CH2-L-T; RP1, RP2, RV1, RV2 are independently selected from hydrogen and fluorine; U is O, S, NH, or N((C1-C24)alkyl); b is a keto-enol tautomer unsaturation; RN1 is selected from H, —(C1-C24)alkyl, —CF3, —CF2CF3, —CCl3, —CBr3, —CHO, and -L-T; RN2 is selected from H, —(C1-C24)alkyl, —CF3, —CF2CF3, —CCl3, —CBr3, and —CHO; RN3 is selected from absent and -alkyl; n is an integer selected from 1, 2, 3, and 4; R4 is absent, or selected from —H, and -L-T; R5 is absent, or selected from —H, and -L-T; at least one of R1, R2, RN1, R4 and R5 is -L-T; each -L- is independently a linker; and wherein each -T is independently selected from a therapeutic agent, a therapeutic anent pro-drug, or a therapeutic agent precursor.