The present invention is generally directed towards compounds capable of binding the aryl hydrocarbon receptor and modulating its activity, methods of treating inflammatory conditions such as Crohn's disease using such compounds, and pharmaceutical compositions comprising such compounds. Also provided are methods of increasing levels of IL-22 in a subject and/or decreasing levels of IFN-γ in a subject.

The present invention is generally directed towards compounds capable of binding the aryl hydrocarbon receptor and modulating its activity, methods of treating inflammatory conditions such as Crohn's disease using such compounds, and pharmaceutical compositions comprising such compounds. Also provided are methods of increasing levels of IL-22 in a subject and/or decreasing levels of IFN-γ in a subject.

The present invention relates to a compound represented by the general formula (I) (wherein the definition of each group has the same meaning as described in the specification). The compound is useful as preventive and/or therapeutic agent for KCNQ2-5 channel-related diseases.

##STR00001##

The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (I): ##STR00001##
wherein: R.sub.1 is H, —OMe, Me, or one or more electron withdrawing groups; R.sub.2 and R.sub.3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R.sub.4 is H or alkyl; R.sub.5 is H or one or more electron donating groups; and n is 1 to 4. The present disclosure further provides compositions comprising a therapeutically effective amount of a compound of general formula (I), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) such compositions to the subject.

The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (I): ##STR00001##
wherein: R.sub.1 is H, —OMe, Me, or one or more electron withdrawing groups; R.sub.2 and R.sub.3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R.sub.4 is H or alkyl; R.sub.5 is H or one or more electron donating groups; and n is 1 to 4. The present disclosure further provides compositions comprising a therapeutically effective amount of a compound of general formula (I), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) such compositions to the subject.

The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (I):

##STR00001##

wherein: R.sub.1 is H, —OMe, Me, or one or more electron withdrawing groups; R.sub.2 and R.sub.3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R.sub.4 is H or alkyl; R.sub.5 is H or one or more electron donating groups; and n is 1 to 4.

The present disclosure further provides compositions comprising a therapeutically effective amount of a compound of general formula (I), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) such compositions to the subject.

The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (I):

##STR00001##

wherein: R.sub.1 is H, —OMe, Me, or one or more electron withdrawing groups; R.sub.2 and R.sub.3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R.sub.4 is H or alkyl; R.sub.5 is H or one or more electron donating groups; and n is 1 to 4.

The present disclosure further provides compositions comprising a therapeutically effective amount of a compound of general formula (I), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) such compositions to the subject.

A compound represented by formula (2) or pharmaceutically acceptable salt thereof:

##STR00001##

wherein R.sup.1 represents a hydrogen atom or the like; R.sup.2 represents a methoxy group or the like; R.sup.3 represents a hydrogen atom or the like; R.sup.4 represents an optionally substituted C.sub.1-6 alkyl group or the like; m represents 0, 1, or 2; n represents 0, 1, 2, or 3; L.sup.1 represents —NH—C(═O)—, —C(═O)—NH—, or the like; L.sup.2 represents a single bond or the like; X represents optionally substituted phenyl or the like; Y represents optionally substituted phenyl or the like; and X and Y are bonded at a carbon atom on each ring.

A compound represented by formula (2) or pharmaceutically acceptable salt thereof:

##STR00001##

wherein R.sup.1 represents a hydrogen atom or the like; R.sup.2 represents a methoxy group or the like; R.sup.3 represents a hydrogen atom or the like; R.sup.4 represents an optionally substituted C.sub.1-6 alkyl group or the like; m represents 0, 1, or 2; n represents 0, 1, 2, or 3; L.sup.1 represents —NH—C(═O)—, —C(═O)—NH—, or the like; L.sup.2 represents a single bond or the like; X represents optionally substituted phenyl or the like; Y represents optionally substituted phenyl or the like; and X and Y are bonded at a carbon atom on each ring.

Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic, cardiovascular, fibrotic, autoimmune/chronic inflammatory diseases, cystic fibrosis, various cancers, neurodegenerative diseases, lipid storage disorders, and ischemia/reperfusion injury, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.