175730-33-3

Upstream product

• 108-31-6 maleic anhydride 
• 89-57-6 5-Aminosalicylic Acid 

Downstream Products

• 75164-01-1 5-(2,5-Dioxo-2,5-dihydro-pyrrol-1-yl)-2-methoxy-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester 

Relevant academic research and scientific papers

Synthesis and characterization of new theophylline and chlordiazepoxide prodrug polymers based on maleimide

In this work, two new drug substituted monomers and new homogenous and heterogeneous polymers were synthesized which loaded with medicinal properties to extend the controlled drug. The first step includes the preparation maleimic acid (L1) and (L2) via re

Design, synthesis, and biochemical evaluation of N-substituted maleimides as inhibitors of prostaglandin endoperoxide synthases

N-(Carboxyalkyl)maleimides are rapid as well as time-dependent inhibitors of prostaglandin endoperoxide synthase (PGHS). The corresponding N- alkylmaleimides were only time-dependent inactivators of PGHS, suggesting that the carboxylate is critical for rapid inhibition. Several N-substituted maleimide analogs containing structural features similar to those of the nonsteroidal anti-inflammatory drug aspirin were synthesized and evaluated as inhibitors of PGHS. Most of the aspirin-like maleimides inactivated the cyclooxygenase activity of purified ovine PGHS-1 in a time- and concentration-dependent manner similar to that of aspirin. The peroxidase activity of PGHS was also inactivated by the maleimide analogs. The cyclooxygenase activity of the inducible isozyme, i.e., PGHS-2, was also inhibited by these compounds. The corresponding succinimide analog of N-5- maleimido-2-acetoxy-1-benzoic acid did not inhibit either enzyme activity, suggesting that inactivation was due to covalent modification of the protein. The mechanism of inhibition of PGHS-1 by N-(carboxyheptyl)maleimide was investigated. Incubation of apoPGHS-1 with 2 equiv of N-(carboxyheptyl)[3,4- 14C]maleimide led to the incorporation of radioactivity in the protein, but no adduct was detected by reversed-phase HPLC, suggesting that it was unstable to the chromatographic conditions. Furthermore, hematin- reconstituted PGHS-1, which was rapidly inhibited by N- (carboxyheptyl)maleimide, displayed spontaneous regeneration of about 50% of the cyclooxygenase and peroxidase activities, suggesting that the adduct responsible for the inhibition breaks down to regenerate active enzyme. ApoPGHS-1, inhibited by N-(carboxyheptyl)maleimide, did not display regeneration of enzyme activity, but addition of hematin to the inhibited apoenzyme led to spontaneous recovery of about 50% of cyclooxygenase activity. These results suggest that addition of heme leads to a conformational change in the protein which increases the susceptibility of the adduct toward hydrolytic cleavage. ApoPGHS-1, pretreated with N(carboxyheptyl)maleimide, was resistant to trypsin cleavage, suggesting that the carboxylate functionality of the maleimide binds in the cyclooxygenase channel. A model for the interaction of N-(carboxyheptyl)maleimide in the cyclooxygenase active site is proposed.

Preparation and Characterization of Hetero-bifunctional Cross-linking Reagents for Protein Modifications

Ten aromatic and aliphatic cross-linking reagents of hetero-bifunctional type were synthesized as part of a search for useful reagents of this type.All of the reagents possess two selectively reactive groups a maleimide group which can combine with a thiol group via its double bond and an N-Hydroxysuccinimidyl ester (one of the most hydrophilic active esters), which can react with an ammmine group.It was found that the active esters of the reagents tested were mostly more reactive with lysine than with leucine, and acylated amino acids more rapidly at pH 8.0 than at pH 7.0.It was also found that the stability of the maleimide group in the compounds tested depends largely upon the pH of the buffer used.The most stable pH was 5.0-6.0.To use one of the present compounds as a cross-linker, the crystalline reagent should be dissolved in tetrahydrofuran of dioxane and the solution used for cross-linking.The acylation step should be carried out first with thiol addition to the maleimide group as the second step.The optimum pH of the buffer used for the first step is slightly basic.The reaction time should be limited to less than 1 hr.When the first step is over, the pH of the reaction mixture should be changed to 5.0-6.0.Keywords---cross-linker; hetero-bifunctional reagent; reactivity of N-hydroxy-succinimidyl ester; stability of maleimide residue; N-(maleimidobenzoyloxy)succinimide derivative; N-(maleimidoalkyloxy)succinimide derivative