579-98-6Relevant academic research and scientific papers
Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride (SASF) Hubs
Barrow, Andrew S.,Cheng, Yunfei,Gialelis, Timothy L.,Giel, Marie-Claire,Kitamura, Seiya,Li, Gencheng,Moses, John E.,Ottonello, Alessandra,Sharpless, K. Barry,Smedley, Christopher J.,Wolan, Dennis W.
, p. 12460 - 12469 (2020/06/10)
Diversity Oriented Clicking (DOC) is a unified click-approach for the modular synthesis of lead-like structures through application of the wide family of click transformations. DOC evolved from the concept of achieving “diversity with ease”, by combining classic C?C π-bond click chemistry with recent developments in connective SuFEx-technologies. We showcase 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs) as a new class of connective hub in concert with a diverse selection of click-cycloaddition processes. Through the selective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click-library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3- and 1,5-dipoles; while reaction with cyclic dienes yields several three-dimensional bicyclic Diels–Alder adducts. Growing the library to 278 discrete compounds through late-stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well-plates—demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin.
Amide derivatives and methods of their use
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Page/Page column 30, (2008/06/13)
Amide derivatives of the general formulae Ia and Ib: are disclosed. Pharmaceutical compositions containing these compounds, and methods for their use, inter alia, for treating and/or preventing gastrointestinal disorders, pain, and pruritus are also disclosed.
A new improved palladium-catalyzed amidocarbonylation
Beller, Matthias,Moradi, Wahed A.,Eckert, Markus,Neumann, Helfried
, p. 4523 - 4526 (2007/10/03)
A new and improved variant of the palladium-catalyzed amidocarbonylation to yield N-acyl-α-amino acids is described. Using Pd/C as catalyst the products were prepared in good to excellent yields (up to 98 %). Advantages of the Pd/C-catalyst with regard to former catalyst systems are demonstrated by the preparation of N-substituted non-natural amino acids which are of current interest as structural units of peptoids.
Synthesis and in Vitro Aldolase Reductase Inhibitory Activity of Compounds Containing an N-Acylglycine Moiety
DeRuiter, Jack,Swearingen, Blake E.,Wandrekar, Vinay,Mayfield, Charles A.
, p. 1033 - 1038 (2007/10/02)
A number of N-benzoylglycines (6), N-acetyl-N-phenylglycines (7), N-benzoyl-N-phenylglycines (8), and tricyclic N-acetic acids (9-12) were synthesized as analogues of the N-acylglycine-containing aldolase reductase inhibitors alrestatin and 2-oxoquinoline-1-acetic acid.Derivatives of 6, which represent ring-simplified analogues of alrestatin, are very weak inhibitors of aldolase reductase obtained from rat lens, producing 50percent inhibition only at concentrations exceeding 100 μM.Compounds of series 7 were designed as ring-opened analogues of the 2-oxoquinolines.While this derivatives are more potent than compounds of series 6 (IC 50s of 6-80 μM), they are less active than the corresponding 2-oxoquinolines.Analogues of series 8 were designed as hybrid structures of both alrestatin and the 2-oxoquinoline-1-acetic acids.These compounds are substantially more potent than compounds of series 6 and 7 and display inhibitory activities comparable to or greater than alrestatin or the 2-oxoquinolines (IC 50s of 0.1-10 μM).Of the rigid analogues of 8, the most potent derivative is benzoxindol (12) with an IC 50 of 0.67 μM, suggesting that fusion of the two aromatic rings of 8 in a coplanar conformation may optimize affinity for aldose reductase in this series.
Process for manufacturing N-acyl derivatives of glycines α-substituted by radicals of aromatic nature and novel products thereof
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, (2008/06/13)
This is an improved process of manufacturing N-acyl derivatives of glycines α-substituted by radicals with an aromatic nature by condensation of the addition product of glyoxylic acid and an amide, with an aromatic compound. In a first stage, the reaction is carried out at low temperature, in a concentrated sulfuric medium, of an aliphatic nitrile of the formula R--C N in which R is a radical selected from the group of substituted and unsubstituted, saturated and unsaturated alkyl radicals, with a concentrated aqueous solution of glyoxylic acid. Then in a second stage, the mixture obtained is condensed also at low temperature with a compound of aromatic nature not including a hydroxyl group and having at least one substitutable free hydrogen, and the resulting product is collected. The concentrated sulfuric acid may be supplemented with acetic acid during the second stage. A surface active agent may be also added in this stage. The products are valuable intermediates for the preparation of semi-synthetic penicillins.
