Provided herein are compounds that are useful in treating cancer.

The present invention relates to sulfonylureas and sulfonylthioureas comprising a 5-membered nitrogen-containing heteroaryl ring attached to the sulfonyl group, wherein the heteroaryl ring is substituted with a nitrogen-containing group R.sup.1′ wherein R.sup.1 contains from 1 to 7 atoms other than hydrogen or halogen. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the inhibition of NLRP.sub.3.

Glutathione deficiencies and deficiencies in glutathione synthetase activity, and therapeutic methods for the treatment thereof.

This disclosure relates to cannabinoid derivatives having the structure of formula (I), pharmaceutical compositions comprising them, and methods of using the cannabinoid derivatives in treating or preventing a diseases associated with a cannabinoid receptor in subject in need thereof, wherein the cannabinoid receptor is one or more of CB1, CB2, 5HT1A, 5HT2A, GPR18, GPR55, GPR119, TRPV1, TRPV2, PPARγ or a μ-opioid receptor.

This disclosure relates to cannabinoid derivatives having the structure of formula (I), pharmaceutical compositions comprising them, and methods of using the cannabinoid derivatives in treating or preventing a diseases associated with a cannabinoid receptor in subject in need thereof, wherein the cannabinoid receptor is one or more of CB1, CB2, 5HT1A, 5HT2A, GPR18, GPR55, GPR119, TRPV1, TRPV2, PPARγ or a μ-opioid receptor.

The invention relates to substituted di-hydro-hydantoin derivatives of the formula (I) wherein X, A, R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds to control or inhibit plant growth.

##STR00001##

The invention relates to substituted di-hydro-hydantoin derivatives of the formula (I) wherein X, A, R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds to control or inhibit plant growth.

##STR00001##

Identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target, Grb2-associated binder˜1 (GAB1), which integrates signals from different signaling pathways and is frequently over-expressed in cancer ceils. Intensive computational modeling is utilized to understand the structure of the GAB1 pleckstrin homology (PH) domain and screened five million compounds. Upon biological evaluation, several inhibitors were found that induced large conformational changes of the target structure exhibited strong selective binding to GAB1 PH domain. Particularly, these inhibitors demonstrated potent and tumor-specific cytotoxicity in breast cancer cells. This targeting GAB1 signaling may be used for cancer therapy, especially for triple negative breast cancer patients.

Identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target, Grb2-associated binder˜1 (GAB1), which integrates signals from different signaling pathways and is frequently over-expressed in cancer ceils. Intensive computational modeling is utilized to understand the structure of the GAB1 pleckstrin homology (PH) domain and screened five million compounds. Upon biological evaluation, several inhibitors were found that induced large conformational changes of the target structure exhibited strong selective binding to GAB1 PH domain. Particularly, these inhibitors demonstrated potent and tumor-specific cytotoxicity in breast cancer cells. This targeting GAB1 signaling may be used for cancer therapy, especially for triple negative breast cancer patients.

The invention provides a process for synthesising a compound of formula V

##STR00001##

wherein: n is 0, 1 or 2; and R is H or

##STR00002##

or a physiologically acceptable salt, tautomer, stereoisomer or mixture of stereoisomers thereof. The process utilizes a N-benzyl protected histidine rather than the unprotected form of histidine. The process of the invention comprises the steps of: (a) deprotecting a N-benzyl protected histidine of formula 11 to form N-benzyl histidine of formula 12; (b) converting compound 12 to (S)-3-(1-benzyl-1H-imidazol-4-yl)-2-(dimethylamino)propanoic acid of formula 13; (c) converting compound 13 to (2S)-N,N,N-2-trimethylethanaminium-3-(1-benzyl-1H-imidazol-4-yl)propanoic acid of formula 14; (d) brominating the imidazole ring of the compound of formula 14 to form 5-bromohercynine lactone (reactive intermediate); and (e) converting the 5-bromohercynine lactone of step (d) to (6-amino-6-carboxyethyl)ergothioneine sulfide of formula 15. The process optionally further includes one of steps (f) to (h): (f) converting the compound of formula 15 to a sulfoxide; (g) converting the compound of formula 15 to a sulfone; or (h) converting the compound of formula 15 to ergothioneine (ESH).