The present invention relates to a compound of formula (Ia), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X-Y is —NHSO.sub.2— or —SO.sub.2NH—; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H, Cl and F; R.sub.5 is selected from H, alkyl, alkynyl, alkenyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, Cl, F, SO.sub.2-alkyl, SO.sub.2NR.sub.13R.sub.14, optionally substituted heteroaryl and alkyl; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H, C.sub.1-C.sub.3-alkyl, or halo; R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azepanyl group, wherein (a) said azepanyl group is substituted by one or more substituents, or (b) one or two carbons in said azepanyl group are replaced by a group selected from O, NH, S and CO, and said azepanyl group is optionally further substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azetidinyl, pyrrolidinyl or piperidinyl group wherein (a) said azetidinyl, pyrrolidinyl or piperidinyl group is substituted by one or more substituents, or (b) one or two carbons in said azetidinyl, pyrrolidinyl or piperidinyl group are replaced by a group selected from NH, S and CO; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an 8, 9 or 10-membered bicyclic heterocycloalkyl group, wherein one or two carbons in the bicyclic heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic heterocycloalkyl group is optionally substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form a 6 to 12-membered bicyclic group containing a spirocyclic carbon atom, wherein one or two carbons in the bicyclic group are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic group is optionally substituted, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group; R.sub.13 and R.sub.14 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

The present invention relates to a method for preparing coumarin compounds substituted by amidoalkyl at 3-position, and related intermediates thereof. The method includes: Step (A): reacting a compound of formula (VI) with a compound of formula (V) to give a compound of formula (VII)

##STR00001## wherein R.sub.1 and R.sub.2 are each independently selected from hydrogen, halogen, and —O(C.sub.1-8 alkyl), wherein the alkyl is optionally substituted with 1 or 2 groups selected from the group consisting of halogen, C.sub.1-8 alkyl substituted with 1-2 hydroxyl groups, —O(C.sub.1-8 alkyl); R.sub.3 is -L-C(O)NR.sub.5R.sub.6, L is C.sub.1-3 alkylene.

Disclosed herein are compounds having a structure of formula (I), compositions and methods useful for the treatment of a disease or infection, such as a viral infection (e.g., Ebola), cancer and obesity: ##STR00001##
wherein A is N or CR.sup.8; Z is ##STR00002## E is selected from optionally substituted alkyl, cycloalkyl, arylalkyl, cycloalkylalkyl, amino, alkoxy, cycloalkyloxy, and cycloalkylamino; R.sup.1 is selected from optionally substituted aryl and heteroaryl, R.sup.2 and R.sup.3 are independently selected from H, deutero, optionally substituted alkyl, haloalkyl, or R.sup.2 and R.sup.3, together with the carbon to which they are bound, combine to form a carbonyl; and R.sup.8 is selected from H, deutero, halo, hydroxyl, cyano, amino, alkyl, alkoxy, carboxy, alkoxycarbonyl, and aminocarbonyl,
provided that E is not ##STR00003##

Disclosed herein are compounds having a structure of formula (I), compositions and methods useful for the treatment of a disease or infection, such as a viral infection (e.g., Ebola), cancer and obesity: ##STR00001##
wherein A is N or CR.sup.8; Z is ##STR00002## E is selected from optionally substituted alkyl, cycloalkyl, arylalkyl, cycloalkylalkyl, amino, alkoxy, cycloalkyloxy, and cycloalkylamino; R.sup.1 is selected from optionally substituted aryl and heteroaryl, R.sup.2 and R.sup.3 are independently selected from H, deutero, optionally substituted alkyl, haloalkyl, or R.sup.2 and R.sup.3, together with the carbon to which they are bound, combine to form a carbonyl; and R.sup.8 is selected from H, deutero, halo, hydroxyl, cyano, amino, alkyl, alkoxy, carboxy, alkoxycarbonyl, and aminocarbonyl,
provided that E is not ##STR00003##

Provided are compounds that inhibit ferroptosis activity, or modulate or inhibit a disease associated with ferroptosis dysregulation, such as neuropathy, ischemia reperfusion injury, acute kidney failure and cancer, including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

The present disclosure provides methadone prodrugs, pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a methadone prodrug that provides enzymatically-controlled release of methadone, and an optional enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of methadone from the prodrug so as to attenuate enzymatic cleavage of the prodrug.

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

Provided in the present invention are a heteroaromatic acetamide derivative and the preparation and the use thereof, wherein the heteroaromatic acetamide derivative is a heteroaromatic acetamide compound as shown in general formula (I), or a pharmaceutically acceptable salt and/or solvate thereof. According to the present invention, experiments have confirmed that the heteroaromatic acetamide derivative of the present invention can specifically bind to transient receptor potential ankyrin 1 (TRPA1) and inhibit or reduce the activity thereof, and can be used for treating diseases mediated by TRPA1. The present invention further provides a method for preparing the heteroaromatic acetamide derivative, and a drug and pharmaceutical composition containing the heteroaromatic acetamide derivative.

##STR00001##

Provided in the present invention are a heteroaromatic acetamide derivative and the preparation and the use thereof, wherein the heteroaromatic acetamide derivative is a heteroaromatic acetamide compound as shown in general formula (I), or a pharmaceutically acceptable salt and/or solvate thereof. According to the present invention, experiments have confirmed that the heteroaromatic acetamide derivative of the present invention can specifically bind to transient receptor potential ankyrin 1 (TRPA1) and inhibit or reduce the activity thereof, and can be used for treating diseases mediated by TRPA1. The present invention further provides a method for preparing the heteroaromatic acetamide derivative, and a drug and pharmaceutical composition containing the heteroaromatic acetamide derivative.

##STR00001##