The present invention relates to disubstituted alkyne derivatives. These compounds are useful for the prevention and/or treatment of several medical conditions including hyperproliferative disorders and diseases.

This document provides compounds that are inhibitors of NF-κB activity, as well as the methods of using such compounds for treating diseases and conditions such as cancer, inflammatory conditions, or autoimmune diseases.

The present invention provides compounds of Formula (I) which can be used as CCR8 inhibitors, which can be used as treatment or prevention of cancer using CCR8 inhibitors targeted tumor specific T regulatory cells.

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The present disclosure relates to using green solvents to synthesize an array of imines, imine-related and imine-derived compounds in an efficient and eco-friendly matter, satisfying green chemistry requirements. Reaction embodiments are performed using solvents, such as ethyl lactate and dimethyl isosorbide, which are both individually characterized as green. In embodiments, solvents include lactic whey and/or water as co-solvents. In these green solvents, the synthesis process discussed herein can produce up to quantitative yields of product at room temperature in a short duration. Embodiments include a method of forming an imine, imine-related or imine-derived compound product. In embodiments, the methods include mixing an aldehyde reactant with a nucleophilic/nitrogen-containing reactant in a green solvent at a temperature between negative twenty degrees Celsius (−20° C.) and positive fifty degrees Celsius (50° C.); stirring the mixture; and forming an imine, imine-related or imine-derived compound product.

The present disclosure relates to using green solvents to synthesize an array of imines, imine-related and imine-derived compounds in an efficient and eco-friendly matter, satisfying green chemistry requirements. Reaction embodiments are performed using solvents, such as ethyl lactate and dimethyl isosorbide, which are both individually characterized as green. In embodiments, solvents include lactic whey and/or water as co-solvents. In these green solvents, the synthesis process discussed herein can produce up to quantitative yields of product at room temperature in a short duration. Embodiments include a method of forming an imine, imine-related or imine-derived compound product. In embodiments, the methods include mixing an aldehyde reactant with a nucleophilic/nitrogen-containing reactant in a green solvent at a temperature between negative twenty degrees Celsius (−20° C.) and positive fifty degrees Celsius (50° C.); stirring the mixture; and forming an imine, imine-related or imine-derived compound product.

The present invention provides a nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof having an inhibitory effect on the production of kynurenine, represented by formula (I):

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(wherein
R.sup.6 and R.sup.7 may be the same or different and each represent a hydrogen atom or the like,
R.sup.8, R.sup.9, R.sup.10, and R.sup.11 may be the same or different and each represent a hydrogen atom or the like,
R.sup.1 represents lower alkyl which may be substituted with cycloalkyl, or the like, and
R.sup.3 represents optionally substituted aryl or an optionally substituted heterocyclic group).

The present invention provides a nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof having an inhibitory effect on the production of kynurenine, represented by formula (I):

##STR00001##

(wherein
R.sup.6 and R.sup.7 may be the same or different and each represent a hydrogen atom or the like,
R.sup.8, R.sup.9, R.sup.10, and R.sup.11 may be the same or different and each represent a hydrogen atom or the like,
R.sup.1 represents lower alkyl which may be substituted with cycloalkyl, or the like, and
R.sup.3 represents optionally substituted aryl or an optionally substituted heterocyclic group).

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):

##STR00001##

or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R.sup.1, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):

##STR00001##

or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R.sup.1, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

The present invention provides new prodrugs of therapeutically active compounds, including oligomeric prodrugs, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.