The present invention relates to compounds according to general formula (I)

##STR00001##

which act as inhibitors of Na.sub.V1.8 and can be used in the treatment of pain.

Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions:

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, and A are defined in the present disclosure. The compounds are potent inhibitors of the main protease (M.sup.pro) of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), and they are useful in treating or preventing COVID-19 in a subject.

A bioorthogonal molecule can include a molecule having a structure according the above wherein R.sup.1-R.sup.8 are independently selected from H, a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, COOH, COOR.sup.9, COR.sup.9, CONR.sup.9R.sup.10, CN, CF.sub.3, and SO.sub.2R.sup.9, and where R.sup.9 and R.sup.10 are independently selected from H and a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, with the proviso that one of R.sup.3-R.sup.8 comprises a leaving group, and wherein X is O, S, N, SO, SO.sub.2, SR.sup.+, Se, PO.sub.2.sup.−, or NRR′.sup.+, and where R and R′ are independently selected from H or a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group. ##STR00001##

A bioorthogonal molecule can include a molecule having a structure according the above wherein R.sup.1-R.sup.8 are independently selected from H, a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, COOH, COOR.sup.9, COR.sup.9, CONR.sup.9R.sup.10, CN, CF.sub.3, and SO.sub.2R.sup.9, and where R.sup.9 and R.sup.10 are independently selected from H and a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, with the proviso that one of R.sup.3-R.sup.8 comprises a leaving group, and wherein X is O, S, N, SO, SO.sub.2, SR.sup.+, Se, PO.sub.2.sup.−, or NRR′.sup.+, and where R and R′ are independently selected from H or a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group. ##STR00001##

The invention provides compounds having STimulator of INterferon Genes (STING) agonistic bioactivity that can be used in the treatment of tumors in patients afflicted therewith. The compounds are of formula (I): as defined herein. Compounds for practice of a method of the invention can be delivered via oral delivery for systemic exposure, as well as delivered intratumorally. Antitumor therapy using a compound of formula (I) can further comprise administration of an effective dose of an immune-checkpoint targeting drug.

The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.

The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.

The present disclosure provides GLP-1R agonists, and compositions, methods, and kits thereof. Such compounds are generally useful for treating a GLP-1R mediated disease or condition in a human.

The present disclosure provides GLP-1R agonists, and compositions, methods, and kits thereof. Such compounds are generally useful for treating a GLP-1R mediated disease or condition in a human.

Disclosed are C16 amide derivatives of C2′-epi-amphotericin B (C2′epiAmB) and amphotericin B (AmB), characterized by improved clinical efficacy with reduced toxicity compared to AmB. Also disclosed are pharmaceutical compositions comprising either type of the C16 amide derivatives, and therapeutic methods of using either type of the C16 amide derivatives; and methods of making the C16 amide derivatives of C2′-epi-amphotericin B.