Provided are compounds of Formula I, or pharmaceutically acceptable salts thereof, which are activators of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) and are useful to treat diseases caused by oxidative stress, such as neurodegenerative diseases or inflammation. Also provided are methods for their use and production.

Provided are compounds of Formula I, or pharmaceutically acceptable salts thereof, which are activators of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) and are useful to treat diseases caused by oxidative stress, such as neurodegenerative diseases or inflammation. Also provided are methods for their use and production.

The present invention provides an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like represented by the following formula (I):

##STR00001##

[wherein, “A” represents optionally substituted heterocyclic diyl, R.sup.1 represents hydrogen atom or optionally substituted lower alkyl, R.sup.2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents —O—, —S—, —SO.sub.2—, —NR.sup.X1— (wherein, R.sup.X1 represents hydrogen atom or lower alkyl), —CHR.sup.X2— (wherein, R.sup.X2 represents hydrogen atom or hydroxy), —CH═CH—, —CO— or —NH—CO—, and n1 and n2 are the same or different, and each represents 0 or 1].

The present invention provides an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like represented by the following formula (I):

##STR00001##

[wherein, “A” represents optionally substituted heterocyclic diyl, R.sup.1 represents hydrogen atom or optionally substituted lower alkyl, R.sup.2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents —O—, —S—, —SO.sub.2—, —NR.sup.X1— (wherein, R.sup.X1 represents hydrogen atom or lower alkyl), —CHR.sup.X2— (wherein, R.sup.X2 represents hydrogen atom or hydroxy), —CH═CH—, —CO— or —NH—CO—, and n1 and n2 are the same or different, and each represents 0 or 1].

Described herein are Δ.sup.9-THC prodrugs, methods of making Δ.sup.9-THC prodrugs, formulations comprising Δ.sup.9-THC prodrugs and methods of using Δ.sup.9-THC. One embodiment described herein relates to the transdermal administration of a Δ.sup.9-THC prodrug for treating and preventing diseases and/or disorders.

Described herein are Δ.sup.9-THC prodrugs, methods of making Δ.sup.9-THC prodrugs, formulations comprising Δ.sup.9-THC prodrugs and methods of using Δ.sup.9-THC. One embodiment described herein relates to the transdermal administration of a Δ.sup.9-THC prodrug for treating and preventing diseases and/or disorders.

The present disclosure relates to compounds, pharmaceutical compositions comprising such compounds, and use of such compounds in methods of treatment or in medicaments for treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including but not limited to misfolded proteins.

Methods of rapidly inhibiting efflux from a cell, sensitizing a drug-resistant cell to a drug and treating a subject with a drug-resistant pathology, by administering tetrahydrocannabinolic acid (THCa), cannabidiol (CBD) or a combination thereof are provided. Pharmaceutical compositions comprising THCa, CBD or a combination thereof and a drug are also provided.

The present invention provides an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like represented by the following formula (I): ##STR00001##
[wherein, “A” represents optionally substituted heterocyclic diyl, R.sup.1 represents hydrogen atom or optionally substituted lower alkyl, R.sup.2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents —O—, —S—, —SO.sub.2—, —NR.sup.X1— (wherein, R.sup.X1 represents hydrogen atom or lower alkyl), —CHR.sup.X2— (wherein, R.sup.X2 represents hydrogen atom or hydroxy), —CH═CH—, —CO— or —NH—CO—, and n1 and n2 are the same or different, and each represents 0 or 1].

The present invention provides an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like represented by the following formula (I): ##STR00001##
[wherein, “A” represents optionally substituted heterocyclic diyl, R.sup.1 represents hydrogen atom or optionally substituted lower alkyl, R.sup.2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents —O—, —S—, —SO.sub.2—, —NR.sup.X1— (wherein, R.sup.X1 represents hydrogen atom or lower alkyl), —CHR.sup.X2— (wherein, R.sup.X2 represents hydrogen atom or hydroxy), —CH═CH—, —CO— or —NH—CO—, and n1 and n2 are the same or different, and each represents 0 or 1].