- Aerobic co-oxidation of hemoglobin and aminoacetone, a putative source of methylglyoxal
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Aminoacetone (1-aminopropan-2-one), a putative minor biological source of methylglyoxal, reacts like other α-aminoketones such as 6-aminolevulinic acid (first heme precursor) and 1,4-diaminobutanone (a microbicide) yielding electrophilic α-oxoaldehydes, ammonium ion and reactive oxygen species by metal- and hemeprotein-catalyzed aerobic oxidation. A plethora of recent reports implicates triose phosphate-generated methylglyoxal in protein crosslinking and DNA addition, leading to age-related disorders, including diabetes. Importantly, methylglyoxal-treated hemoglobin adds four water-exposed arginine residues, which may compromise its physiological role and potentially serve as biomarkers for diabetes. This paper reports on the co-oxidation of aminoacetone and oxyhemoglobin in normally aerated phosphate buffer, leading to structural changes in hemoglobin, which can be attributed to the addition of aminoacetone-produced methylglyoxal to the protein. Hydroxyl radical-promoted chemical damage to hemoglobin may also occur in parallel, which is suggested by EPR-spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide and ethanol. Concomitantly, oxyhemoglobin is oxidized to methemoglobin, as indicated by characteristic CD spectral changes in the Soret and visible regions. Overall, these findings may contribute to elucidate the molecular mechanisms underlying human diseases associated with hemoglobin dysfunctions and with aminoacetone in metabolic alterations related to excess glycine and threonine.
- Ramos, Luiz D.,Mantovani, Mariana C.,Sartori, Adriano,Dutra, Fernando,Stevani, Cassius V.,Bechara, Etelvino J.H.
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Read Online
- The Wacker-type oxidation of allylamine
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Wacker-type oxidation of allylamine in acid solution can be used to produce 1-aminopropan-2-one hydrochloride, 1, in yields ranging from 26 to 42percent depending on reaction conditions.However, the difficulty of its separation from the hyproducts limits the scope of this reaction.
- Kaufmann, Werner,Venanzi, Luigi M.
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Read Online
- Synthesis method for medicine raw material aminoacetone hydrochloride
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The invention relates to a practical synthesis method for preparing an important medicine raw material aminoacetone hydrochloride. The method comprises the following steps: glycine used as a raw material reacts with acetic anhydride and pyridine in a refluxing state to obtain acetyl protected aminoacetone; and the acetyl protected aminoacetone is hydrolyzed to obtain the aminoacetone hydrochloride.
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Paragraph 0009; 0015; 0016
(2018/04/21)
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- High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors
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The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57-617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure-activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38α kinase.
- Myers, Stephanie M.,Bawn, Ruth H.,Bisset, Louise C.,Blackburn, Timothy J.,Cottyn, Betty,Molyneux, Lauren,Wong, Ai-Ching,Cano, Celine,Clegg, William,Harrington, Ross. W.,Leung, Hing,Rigoreau, Laurent,Vidot, Sandrine,Golding, Bernard T.,Griffin, Roger J.,Hammonds, Tim,Newell, David R.,Hardcastle, Ian R.
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supporting information
p. 444 - 455
(2016/08/16)
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- NOVEL HIGH AFFINITY QUINOLINE-BASED KINASE LIGANDS
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Quinoline-based inhibitors of cyclin dependent kinase 2, compositions including the inhibitors, and methods of using the inhibitors and inhibitor compositions are described. The inhibitors and compositions including them are useful for treating disease or disease symptoms. The invention also provides for methods of making CDK-2 inhibitor compounds, methods of inhibiting CDK-2, and methods for treating disease or disease symptoms.
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Paragraph 0220
(2014/01/09)
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- Rearrangement of N-tert-butanesulfinyl α-halo imines with alkoxides to N-tert-butanesulfinyl 2-amino acetals as precursors of N-protected and N-unprotected α-amino carbonyl compounds
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Reaction of N-tert-butanesulfinyl α-halo imines with alkoxides afforded new N-tert-butanesulfinyl 2-amino acetals in good to excellent yield. These N-tert-butanesulfinyl 2-amino acetals are convenient precursors for the TMSOTf-promoted synthesis of the co
- Colpaert, Filip,Mangelinckx, Sven,Denolf, Bram,De Kimpe, Norbert
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experimental part
p. 6023 - 6032
(2012/10/08)
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- A small molecule that mimics the metabolic activity of copper-containing amine oxidases (CuAOs) toward physiological mono- and polyamines
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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.
- Largeron, Martine,Fleury, Maurice-Bernard,Strolin Benedetti, Margherita
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scheme or table
p. 3796 - 3800
(2010/09/06)
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- Novel high affinity quinoline-based kinase ligands
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Quinoline-based inhibitors of cyclin dependent kinase 2, compositions including the inhibitors, and methods of using the inhibitors and inhibitor compositions are described. The inhibitors and compositions including them are useful for treating disease or disease symptoms. The invention also provides for methods of making CDK-2 inhibitor compounds, methods of inhibiting CDK-2, and methods for treating disease or disease symptoms.
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Page/Page column 92
(2008/06/13)
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- 2-ARYLTHIAZOLE DERIVATIVES AS CXCR3 RECEPTOR MODULATORS
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The invention encompasses compounds of Formula I or pharmaceutically acceptable salts thereof, which are modulators of the CXCR3 chemokine receptor function useful for the treatment or prevention of pathogenic inflammatory processes, autoimmune diseases or graft rejection processes. Methods of use and pharmaceutical compositions are also encompassed.
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Page/Page column 69
(2010/11/28)
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- Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes
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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.
- Cui, Peng,Macdonald, Timothy L.,Chen, Meng,Nadler, Jerry L.
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p. 3401 - 3405
(2007/10/03)
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- Electrolytic Oxidation of Ketones in Ammoniacal Methanol in the Presence of Catalytic Amounts of KI
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The indirect electrooxidation of ketones in ammoniacal methanol using iodide ion as a mediator afforded 2,2-dialkyl-2,5-dihydro-1H-imidazoles 3 via an oxidative cyclocoupling of ketimine intermediates formed from ketones and ammonia.The treatment of 3 with dilute HCl gave α-amino ketone hydrochlorides 4 and the parent ketones in good yields.A similar electrooxidation of 3 resulted in the formation of the corresponding 2H-imidazoles 6, which were hydrolyzed to α-diketones and the parent ketones.The same products 6 could also conveniently be obtained by chemical oxidation of 3 with aqueous NaOCl.
- Chiba, Toshiro,Sakagami, Hirotoshi,Murata, Miki,Okimoto, Mitsuhiro
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p. 6764 - 6770
(2007/10/03)
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- A Convenient Synthesis of Aminomethyl Ketones (α-Amino Ketones)
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Several N,N-diformylaminomethyl ketones 3 were prepared by treating the respective bromomethylketone 1 with sodium diformylamide in acetonitrile at room temperature.This reaction produced from N-formylaminomethyl ketones 4 when ethanol was used as the solvent.One of the formyl groups of N,N-difomylaminomethyl ketones was selectively removed by using a catalytic amount of sodium or potassium hydroxide in alcohol to the corresponding N-formylaminomethyl ketones 4.The formyl groups of both N,N-diformyl- and N-formylaminomethyl ketones could be easily removed by either5percent hydrochloric acid in ethanol or 6N hydrochloric acid to give the corresponding aminomethyl ketone hydrochlorides 5.These reactions are general and give high yield of the products.
- Yinglin, Han,Hongwen, Hu
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p. 615 - 618
(2007/10/02)
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- Lipophilic 5,6,7,8-tetrahydropterin substrates for phenylalanine hydroxylase (monkey brain), tryptophan hydroxylase (rat brain) and tyrosine hydroxylase (rat brain)
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A high yielding unambiguous synthesis of (+/-)-6-alkyl-5,6,7,8-tetrahydropterin 5a-f hydrochlorides starting from ethyl α-isocyanoacetate 1 and the respective alkanoic anhydrides or alkanoyl chlorides in four steps is described.All the six pterins 5a-f that have been synthesised are substrates for mammalian phenylalanine, tryptophan and tyrosine hydroxylases and their activities have been compared with those of natural 6R-tetrahydrobiopterin under similar conditions.The data allowed the choice of 6-n-propyl-5,6,7,8-tetrahydropterin 5c for further studies as a candidate for tetrahydrobiopterin drug therapy.Keywords: (+/-)-6-alkyltetrahydropterinsydroxylase / tryptophan hydroxylase / tyrosine hydroxylase
- Armarego, Wilfred L. F.,Taguchi, Hiroyasu,Cotton, Richard G. H.,Battiston, Sandra,Leong, Lillian
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p. 283 - 292
(2007/10/02)
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- α-Amino Ketones - A Contribution to the Synthesis of Optically Active Derivatives of Amino Acids and Peptides
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The synthesis of N-Z-protected methyl ketones from amino acids via the chloromethyl ketones and dehalogenation of the latter with zinc in glacial acetic acid is described.Deprotection of the methyl ketones results in the formation of hydrohalogenides of the α-aminoalkyl methyl ketones further converted to N-acylated peptide ketones as analogs of peptide hormones or as competitively acting substrate analogs of proteolytic enzymes.Aminoacetone is conveniently prepared as well as methyl-pyrrolidyl ketone and methyl-piperidyl ketone.
- Fittkau, Siegfried,Jahreis, Guenther,Peters, Klaus,Balaspiri, Lajos
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p. 529 - 538
(2007/10/02)
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