Described herein are compounds of Formula I:

##STR00001##

wherein R.sub.1-R.sub.6 are as described herein, for use in the treatment of a coronavirus infection; a method of inhibiting a coronavirus 3CL protease, by contacting the 3CL protease with a compound of Formula I; as well as methods pharmaceutical composition comprising a compound of Formula I and at least one phospholipid, wherein a weight ratio of the phospholipid(s) to the compound in the composition is in a range of from 10:1 to 1:10. Further described herein is a method of treating a coronavirus infection in a subject in need thereof, by administering to the subject at least one compound that exhibits at least two of: inhibition of an activity of a 3CL protease of the coronavirus; inhibition of inflammation in the subject; and inhibition of autophagy in the subject.

Compositions and methods are provided for decreasing processing of chondroitin sulfate proteoglycan 4 (CSPG) in treatment of gliomas, which treatment may be combined with administration of an immune-oncology agent.

Compositions and methods are provided for decreasing processing of chondroitin sulfate proteoglycan 4 (CSPG) in treatment of gliomas, which treatment may be combined with administration of an immune-oncology agent.

Combination therapy methods, compositions and kits Invention relates to combinations comprising: a) a compound of formula (I)

##STR00001##

or a pharmaceutically or veterinary acceptable salt thereof, wherein:
R.sub.1 R.sub.2 and R.sub.3 have particular meaning; and (b) one or more drugs selected from the group consisting of i) a compound of formula (IV), or a pharmaceutically or veterinary acceptable salt thereof,

##STR00002##

wherein R.sub.5 and R.sub.6 have particular meaning, ii) a sphingosine-1-phosphate receptor inhibitor (S1PR modulator), and iii) a Signal transducer and activator of transcription 3 (STAT3) inhibitor. Particular combinations and single pharmaceutical compositions and kits of parts are disclosed. These combinations, single pharmaceutical compositions and kits of parts are for use in the treatment and/or prevention of an inflammatory neurological disease or condition which can result in the destruction or degeneration of axons or myelin in a subject in need thereof

Combination therapy methods, compositions and kits Invention relates to combinations comprising: a) a compound of formula (I)

##STR00001##

or a pharmaceutically or veterinary acceptable salt thereof, wherein:
R.sub.1 R.sub.2 and R.sub.3 have particular meaning; and (b) one or more drugs selected from the group consisting of i) a compound of formula (IV), or a pharmaceutically or veterinary acceptable salt thereof,

##STR00002##

wherein R.sub.5 and R.sub.6 have particular meaning, ii) a sphingosine-1-phosphate receptor inhibitor (S1PR modulator), and iii) a Signal transducer and activator of transcription 3 (STAT3) inhibitor. Particular combinations and single pharmaceutical compositions and kits of parts are disclosed. These combinations, single pharmaceutical compositions and kits of parts are for use in the treatment and/or prevention of an inflammatory neurological disease or condition which can result in the destruction or degeneration of axons or myelin in a subject in need thereof

A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, and a heterocyclic ring, wherein ring A is selected from the group consisting of a benzene ring, a naphthalene ring, a quinoxaline ring, a thiophene ring, an indole ring, a benzothiophene ring, an imidazole ring, a quinoline ring, a quinazoline ring, and a pyridine ring; X, R.sup.1 and R.sup.2 represent a substituent on a ring atom constituting ring A, wherein R.sup.1 and R.sup.2 are bonded to adjacent ring atoms of ring A; m represents an integer of 1 or 2; X is a halogen atom, and when m is 2, each X is the same or different; R.sup.1 and R.sup.2 are the same or different; R.sup.1 and R.sup.2 independently represent a group represented from the following groups:

—(CH.sub.2).sub.n—Y—R.sup.4

wherein Y is selected from the group consisting of O, S, SO, SO.sub.2, and Se, n represents an integer of 1 to 8, R.sup.4 represents

##STR00001##

wherein R.sup.41, R.sup.42 and R.sup.47 are the same and are a hydrogen atom

##STR00002##

A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, and a heterocyclic ring, wherein ring A is selected from the group consisting of a benzene ring, a naphthalene ring, a quinoxaline ring, a thiophene ring, an indole ring, a benzothiophene ring, an imidazole ring, a quinoline ring, a quinazoline ring, and a pyridine ring; X, R.sup.1 and R.sup.2 represent a substituent on a ring atom constituting ring A, wherein R.sup.1 and R.sup.2 are bonded to adjacent ring atoms of ring A; m represents an integer of 1 or 2; X is a halogen atom, and when m is 2, each X is the same or different; R.sup.1 and R.sup.2 are the same or different; R.sup.1 and R.sup.2 independently represent a group represented from the following groups:

—(CH.sub.2).sub.n—Y—R.sup.4

wherein Y is selected from the group consisting of O, S, SO, SO.sub.2, and Se, n represents an integer of 1 to 8, R.sup.4 represents

##STR00001##

wherein R.sup.41, R.sup.42 and R.sup.47 are the same and are a hydrogen atom

##STR00002##

The invention provides new methods of treating patients benefiting from increased blood levels of alpha-lipoic acid. Such patients may include those suffering from various physiological disorders such as diabetic neuropathy. A dissolvable tablet, not meant to be swallowed, comprising alpha-lipoic acid in a limited release matrix provides means of administering therapeutically beneficial concentrations of alpha-lipoic acid without the commonly associated oral burn. Due to its orally dissolvable nature, this rate limiting matrix can deliver approximately IV-equivalent plasma levels of thioctic acid.

The invention provides new methods of treating patients benefiting from increased blood levels of alpha-lipoic acid. Such patients may include those suffering from various physiological disorders such as diabetic neuropathy. A dissolvable tablet, not meant to be swallowed, comprising alpha-lipoic acid in a limited release matrix provides means of administering therapeutically beneficial concentrations of alpha-lipoic acid without the commonly associated oral burn. Due to its orally dissolvable nature, this rate limiting matrix can deliver approximately IV-equivalent plasma levels of thioctic acid.

Exemplary methods, compositions, kits and uses thereof for treating neoplasia are provided. For example, a method can be provided for treating neoplasia in a subject, including administering to the subject a VRK2 (vaccinia-related kinase 2) inhibitor, alone or in combination with an inhibitor of Programmed cell death receptor-1 (PD-1). The exemplary methods, compositions and kits may improve cancer immunotherapy.