87766-32-3Relevant academic research and scientific papers
Protecting-Group-Free Amidation of Amino Acids using Lewis Acid Catalysts
Sabatini, Marco T.,Karaluka, Valerija,Lanigan, Rachel M.,Boulton, Lee T.,Badland, Matthew,Sheppard, Tom D.
supporting information, p. 7033 - 7043 (2018/05/04)
Amidation of unprotected amino acids has been investigated using a variety of ‘classical“ coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions.
SMALL MOLECULES AGAINST CEREBLON TO ENHANCE EFFECTOR T CELL FUNCTION
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Page/Page column 156-157, (2017/10/11)
Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.
Discovery of highly functionalized scaffolds: Pyrroloimidazolediones as P2X7 receptor antagonists
Homerin, Germain,Lipka, Emmanuelle,Rigo, Beno?t,Millet, Régis,Dezitter, Xavier,Furman, Christophe,Ghinet, Alina
supporting information, p. 5327 - 5336 (2017/08/04)
A broad range of pyrroloimidazolediones, new highly functionalized bicyclic heterocycles, was obtained by a cycloaddition reaction between L-pyroglutamide derivatives and Bredereck's reagent. Methanolysis of subsequent pyrroloimidazolediones provided antagonists of P2X7 receptor, with retention of initial stereoconfiguration, with potential applications in the treatment of inflammatory and neurological diseases. We have thus developed a new synthesis of lactamic nitrogen free enaminones which is currently the easiest method cited in the literature to access these compounds.
On the discovery of new potent human farnesyltransferase inhibitors: Emerging pyroglutamic derivatives
Homerin, Germain,Lipka, Emmanuelle,Rigo, Beno?t,Farce, Amaury,Dubois, Jo?lle,Ghinet, Alina
, p. 8110 - 8118 (2017/10/10)
In the current context of lack of emergence of innovative human farnesyltransferase inhibitors families, and given all new therapeutic perspectives that open up for such molecules in rare diseases (e.g. Hutchinson-Gilford progeria syndrome), and in delta hepatitis, cardiovascular or neuroinflammatory diseases, we have just discovered a new series of powerful inhibitors. These molecules are pyroglutamic acid derivatives, and were evaluated on human farnesyltransferase in vitro then modeled in silico on the active site of the protein. Three main points of the pyroglutamic acid cycle have undergone chemical modulations pyroglutamides in position 5 (compounds 7a-h), constrained bicyclic analogues of pyrroloimidazoledione type (compounds 1a-h), modulation of the position 3 (compounds 2-5 and 8), and allowed the first SAR in the field. Five derivatives in the current work have IC50 values in the small nanomolar range (2-5 nM). These new lead compounds open the way for the next generation of farnesyltransferase inhibitors.
B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether
Karaluka, Valerija,Lanigan, Rachel M.,Murray, Paul M.,Badland, Matthew,Sheppard, Tom D.
supporting information, p. 10888 - 10894 (2015/11/17)
The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.
XtalFluor-E, an efficient coupling reagent for amidation of carboxylic acids
Orliac, Aurélie,Gomez Pardo, Domingo,Bombrun, Agnès,Cossy, Janine
supporting information, p. 902 - 905 (2013/03/29)
Amides were produced from carboxylic acids and amines by using XtalFluor-E as an activator. Even poorly reactive carboxylic acids can be transformed to amides. In addition, optically active amines and/or carboxylic acids were not epimerized/racemized during the process.
Design and synthesis of potent inhibitor of apoptosis (IAP) proteins antagonists bearing an octahydropyrrolo[1,2-a]pyrazine scaffold as a novel proline mimetic
Hashimoto, Kentaro,Saito, Bunnai,Miyamoto, Naoki,Oguro, Yuya,Tomita, Daisuke,Shiokawa, Zenyu,Asano, Moriteru,Kakei, Hiroyuki,Taya, Naohiro,Kawasaki, Masanori,Sumi, Hiroyuki,Yabuki, Masato,Iwai, Kenichi,Yoshida, Sei,Yoshimatsu, Mie,Aoyama, Kazunobu,Kosugi, Yohei,Kojima, Takashi,Morishita, Nao,Dougan, Douglas R.,Snell, Gyorgy P.,Imamura, Shinichi,Ishikawa, Tomoyasu
, p. 1228 - 1246 (2013/03/28)
To develop novel inhibitor of apoptosis (IAP) proteins antagonists, we designed a bicyclic octahydropyrrolo[1,2-a]pyrazine scaffold as a novel proline bioisostere. This design was based on the X-ray co-crystal structure of four N-terminal amino acid residues (AVPI) of the second mitochondria-derived activator of caspase (Smac) with the X-chromosome-linked IAP (XIAP) protein. Lead optimization of this scaffold to improve oral absorption yielded compound 45, which showed potent cellular IAP1 (cIAP1 IC50: 1.3 nM) and XIAP (IC50: 200 nM) inhibitory activity, in addition to potent tumor growth inhibitory activity (GI50: 1.8 nM) in MDA-MB-231 breast cancer cells. X-ray crystallographic analysis of compound 45 bound to XIAP and to cIAP1 was achieved, revealing the various key interactions that contribute to the higher cIAPI affinity of compound 45 over XIAP. Because of its potent IAP inhibitory activities, compound 45 (T-3256336) caused tumor regression in a MDA-MB-231 tumor xenograft model (T/C: -53% at 30 mg/kg).
Heterocyclic Compound
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Page/Page column 73, (2011/02/26)
The present invention provides a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof. The compound of the present invention shows a strong IAP antagonistic activity.
Iridium-catalyzed X-H insertions of sulfoxonium ylides
Mangion, Ian K.,Nwamba, Ikenna K.,Shevlin, Michael,Huffman, Mark A.
supporting information; experimental part, p. 3566 - 3569 (2011/02/22)
Image Persented The unique reactivity of sulfoxonium ylides as a carbene source is described for a variety of X-H bond insertions, taking advantage of a simple, commercially available iridium catalyst. This method has applications in both intra- and intermolecular reactivity, including a practical ring-expansion strategy for lactams. The safety and stability of sulfoxonium ylides recommend them as preferable surrogates to traditional diazo ketones and esters.
Synthesis and characterization of chiral 1,2-diamines from 5-oxo-pyrrolidine-(S)-2-carboxylic acid
Koehn, Uwe,Schramm, Andrea,Kloss, Florian,Goerls, Helmar,Arnold, Evelyn,Anders, Ernst
, p. 1735 - 1741 (2008/02/11)
Unsymmetrical chiral secondary vicinal diamines were synthesized by applying a modified three-step reaction. The key step in this sequence is a primary amine mediated ring opening reaction of a diastereomeric oxazolidinone derivative. A possible mechanism
