| abstract |
The invention relates to a process for the manufacture of substituted maleimides of the formula <IMAGE> (I) wherein R1 is alkyl, aryl or heteroaryl and R2 is hydrogen, alkyl, alkoxycarbonyl, aryl or heteroaryl, by reacting an activated glyoxylate of the formula <IMAGE> (II) wherein R1 has the above significance and X is a leaving atom or group, with an imidate of the formula <IMAGE> (III) wherein R2 has the above significance, R3 is alkyl, aryl or trialkylsilyl and Y is oxygen or sulfur, in the presence of a base and, after treating the resulting reaction product obtained in which R2 is hydrogen or alkyl with a strong base, hydrolyzing and dehydrating the resulting hydroxy-pyrrolinone of the formula <IMAGE> (IV) wherein R1, R2, R3 and Y have the above significance. The substituted maleimides of formula I are pharmacologically active, for example as protein kinase C inhibitors and which a useful, for example, in the treatment and prophylaxis of inflammatory, immunological, bronchopulmonary and cardiovascular disorders, or as antiproliferative agents useful, for example, in the treatment of immune diseases and allergic disorders. |