Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

The invention provides novel compounds having the general formula (I) ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, A, X and R.sup.11 are as described herein, compositions including the compounds and methods of using the compounds.

The present invention is related to the use of HMGB1 antagonists such as K883 in the treatment and/or prevention and/or inhibition of severe sepsis in mammals, e.g., humans, and pharmaceutical compositions for the same comprising HMGB1 antagonists in an effective amount to treat and/or prevent and/or inhibit this condition.

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.

The present invention is related to HMGB1 antagonists and, in particular, HMGB1 tetramer peptidomimetics which have been stabilized with at least one azatide linkage, such as K883. The present invention is also related to pharmaceutical compositions comprising HMGB1 antagonists such as K883.

The present invention is related to the use of HMGB1 antagonists, specifically derivatives of K883 in the treatment and/or prevention and/or inhibition of neuropathy pain, and in particular diabetic neuropathy in mammals, e.g., humans, and pharmaceutical compositions for the same comprising HMGB1 antagonists in an effective amount to treat and/or prevent and/or inhibit this condition.

The present invention is related to the use of HMGB1 antagonists in the treatment and/or prevention and/or inhibition of acute lung injury in mammals, e.g., humans, and pharmaceutical compositions for the same comprising HMGB1 antagonists, in particular K883, in an effective amount to treat and/or prevent and/or inhibit this condition.

The present invention relates to a compound of formula (I), wherein X is CO, CS or BOH; Y is an electrophile and Z is a leaving group, or YZ is an electrophile; R.sup.1 comprises or consists of (a) (i) a first group binding to a proteolytic site of a proteasome, said first group being bound to X; and (ii) optionally a second group enhancing delivery; or (b) a group binding between subunits 1 and 2 of a proteasome; R.sup.2 and R.sup.3 are independently selected from H, methyl, methoxy, ethyl, ethenyl, ethinyl and cyano, wherein methyl and ethyl maybe substituted with OH or halogen.

##STR00001##

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.

The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compound that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to the prevention and treatment of Alzheimer's disease