The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II):

##STR00001##

comprising treating a compound of Formula (I):

##STR00002##

with a transition metal catalyst and under alkylation conditions as valence and stability permit.

The present invention relates to a medicament for treating or preventing a disease related to orexin receptor, especially orexin type 2 receptor, comprising a new compound having a urea structure or a pharmaceutically acceptable salt thereof as an active ingredient. In more detail, the present invention relates to a medicament for treating or preventing narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, etc.

The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), 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 invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), 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.

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##

Methods of hydromethylation of alkenes and ketones, including methods that use Tebbe's reagent. The methods may include contacting Cp.sub.2Ti(μ-Cl)(μ-CH.sub.2)AlMe.sub.2 and an alkene or a ketone to produce an intermediate product that may include a titanacyclobutane. The intermediate product may be contacted with an acid to produce a methylated product.

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.

##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##

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##