23734-86-3Relevant academic research and scientific papers
Synthesis and antiherpetic activity of novel purine conjugates with 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine
Andronova, Valeriya L.,Charushin, Valery N.,Galegov, Georgii А.,Krasnov, Victor P.,Levit, Galina L.,Vozdvizhenskaya, Olga А.
, p. 490 - 497 (2021/06/26)
[Figure not available: see fulltext.] A method for the synthesis of novel purine conjugates with 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine containing fragments of ω-amino acids with different lengths of the polymethylene chain as a linker has been developed. It was found in experiments in vitro that the obtained compounds are active against the herpes simplex virus type 1, including the acyclovir-resistant strain.
Transformations of higher terpenoids: IV. Synthesis and spectral parameters of glycyrrhetinic acid derivatives containing amino acid fragments
Petrenko,Petukhova,Shakirov,Shul'ts,Tolstikov
, p. 982 - 995 (2007/10/03)
New glycyrrhetinic acid derivatives containing amino acid and amino ester fragments were synthesized as potential biologically active substances. NMR spectra of the newly synthesized compounds were studied, and assignment of signals of the C8 and C14 carbon atoms in the terpenoid fragment was refined.
Design, synthesis, and biochemical evaluation of N-substituted maleimides as inhibitors of prostaglandin endoperoxide synthases
Kalgutkar, Amit S.,Crews, Brenda C.,Marnett, Lawrence J.
, p. 1692 - 1703 (2007/10/03)
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.
