131713-50-3Relevant articles and documents
Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes
Cui, Peng,Macdonald, Timothy L.,Chen, Meng,Nadler, Jerry L.
, p. 3401 - 3405 (2006)
Lisofylline (LSF, 1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine) is an anti-inflammatory agent that protects β-cells from Th1 cytokine-induced dysfunction and reduces the onset of Type 1 diabetes in non-obese diabetic (NOD) mice. Due to its low potency, poor oral bioavailability, and short half-life, the widespread clinical utility of LSF may be limited. Our goal has been to develop new agents based on the LSF structural motif that resolve the potency and pharmacokinetic liabilities of LSF. In this study, we have generated a focused library of LSF analogs that maintain the side chain (5-R-hydroxyhexyl) constant, while substituting a variety of nitrogen-containing heterocyclic substructures for the xanthine moiety of LSF. This library includes the xanthine-like (5-aza-7-deazaxanthine), as well as non-xanthine-like skeletons. The LSF analogs were evaluated in a pancreatic β-cell line for the effects on apoptosis protection and insulin release. The metabolic stability of selected compounds was also tested.
A small molecule that mimics the metabolic activity of copper-containing amine oxidases (CuAOs) toward physiological mono- and polyamines
Largeron, Martine,Fleury, Maurice-Bernard,Strolin Benedetti, Margherita
scheme or table, p. 3796 - 3800 (2010/09/06)
Primary aliphatic biogenic amines have been successfully oxidized using a quinonoid species that mimics the metabolic activity of copper-containing amine oxidase (CuAO) enzymes. Especially, high catalytic performances were observed with aminoacetone, a threonine catabolite, and methylamine, a metabolite of adrenaline, and with the primary amino groups of putrescine and spermidine which are both decarboxylation products of ornithine and S-adenosyl-methionine. Furthermore, contrary to flavine adenine dinucleotide (FAD)-dependent amine oxidase enzymes, no activity was found toward secondary and tertiary amines.
Molecular transporter between polymer platforms: Highly efficient chemoenzymatic glycopeptide synthesis by the combined use of solid-phase and water-soluble polymer supports
Fumoto, Masataka,Hinou, Hiroshi,Matsushita, Takahiko,Kurogochi, Masaki,Ohta, Takashi,Ito, Takaomi,Yamada, Kuriko,Takimoto, Akio,Kondo, Hirosato,Inazu, Toshiyuki,Nishimura, Shin-Ichiro
, p. 2534 - 2537 (2007/10/03)
(Figure Presented) The molecule standing at platform one ...: Rapid glycopeptide synthesis is achieved with a heterobifunctional "molecular transporter" (see scheme), which interfaces two types of polymer platforms for combined chemical and enzymatic synt
Peptidyl and azapeptidyl methylketones as substrate analog inhibitors of papin and cathepsin B
Calabretta, R.,Giordano, C.,Gallina, C.,Morea, V.,Consalvi, V.,Scandurra, R.
, p. 931 - 942 (2007/10/03)
Peptidyl methylketones containing Phe, Tyr, Tyr(I), Tyr(I2), Leu and Ile in P2 were synthesized and tested as substrate analog revesible of papain and bovine spleen cathepsin B.The most effective cathepsin B inhibitor contained Tyr(I2) and displayed an inhibition constant of 4.7 μM at pH 6.8 and 25 deg C, while Leu or Ile gave practically inert analogs.Replacement of the amino acids in P2 with the analogues α-azaamino acids, as well as the glycine in P1 with α-azaglycine, led to complete loss of inhibiting activity.Introducing alkoxy substituents at themethyl adjacent to the ketone group generally resulted in more effective inhibitors, with inhibition constants in the micromolar range for both papin and cathepsin B. - Keywords: enzyme inhibiting activity; cysteine proptease; slow binding; peptidyl methylketone; azapeptidyl methylketone; papain; cathepsin B
