Inhibitors of HBV replication of Formula (I) ##STR00001##
including stereochemically isomeric forms, salts, hydrates and solvates thereof, wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HBV inhibitors, in HBV therapy.

Provided herein are, inter alia, compounds inhibiting poly(ADP-ribose) Glycohydrolase (PARG) in a cancer cell and methods of treating cancer using compounds of the invention.

Provided herein are, inter alia, compounds inhibiting poly(ADP-ribose) Glycohydrolase (PARG) in a cancer cell and methods of treating cancer using compounds of the invention.

Disclosed are a mild and efficient preparation method for an -acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The -acyloxyenamide compound is obtained by an addition reaction of a ynamide and a carboxylic acid in dichloromethane under conditions where the temperature is 0 C. to 50 C.; the produced -acyloxyenamide compound can react with an amine compound to produce an amide or a polypeptide; the two reactions can be carried out step by step, and can also be carried out in one pot. According to the invention, the reaction conditions are mild and no metal catalyst is required; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; and the operation is simple and the application range is wide.

Disclosed are a mild and efficient preparation method for an -acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The -acyloxyenamide compound is obtained by an addition reaction of a ynamide and a carboxylic acid in dichloromethane under conditions where the temperature is 0 C. to 50 C.; the produced -acyloxyenamide compound can react with an amine compound to produce an amide or a polypeptide; the two reactions can be carried out step by step, and can also be carried out in one pot. According to the invention, the reaction conditions are mild and no metal catalyst is required; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; and the operation is simple and the application range is wide.

Disclosed are a mild and efficient preparation method for an -acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The -acyloxyenamide compound is obtained by an addition reaction of a ynamide and a carboxylic acid in dichloromethane under conditions where the temperature is 0 C. to 50 C.; the produced -acyloxyenamide compound can react with an amine compound to produce an amide or a polypeptide; the two reactions can be carried out step by step, and can also be carried out in one pot. According to the invention, the reaction conditions are mild and no metal catalyst is required; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; and the operation is simple and the application range is wide.

Disclosed are a mild and efficient preparation method for an -acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The -acyloxyenamide compound is obtained by an addition reaction of a ynamide and a carboxylic acid in dichloromethane under conditions where the temperature is 0 C. to 50 C.; the produced -acyloxyenamide compound can react with an amine compound to produce an amide or a polypeptide; the two reactions can be carried out step by step, and can also be carried out in one pot. According to the invention, the reaction conditions are mild and no metal catalyst is required; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; and the operation is simple and the application range is wide.

Disclosed are a mild and efficient preparation method for an -acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The -acyloxyenamide compound is obtained by an addition reaction of a ynamide and a carboxylic acid in dichloromethane under conditions where the temperature is 0 C. to 50 C.; the produced -acyloxyenamide compound can react with an amine compound to produce an amide or a polypeptide; the two reactions can be carried out step by step, and can also be carried out in one pot. According to the invention, the reaction conditions are mild and no metal catalyst is required; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; and the operation is simple and the application range is wide.

Disclosed are a mild and efficient preparation method for an -acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The -acyloxyenamide compound is obtained by an addition reaction of a ynamide and a carboxylic acid in dichloromethane under conditions where the temperature is 0 C. to 50 C.; the produced -acyloxyenamide compound can react with an amine compound to produce an amide or a polypeptide; the two reactions can be carried out step by step, and can also be carried out in one pot. According to the invention, the reaction conditions are mild and no metal catalyst is required; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; and the operation is simple and the application range is wide.

Described herein are compounds and compositions for the amelioration of arthritis or joint injuries by inducing mesenchymal stem cells into chondrocytes.