74796-19-3Relevant academic research and scientific papers
Intramolecular Cycloaddition of (Allylimino)ketens: Access to 3-Azabicyclohept-2-en-7-ones
Maujean, Alain,Marcy, Guy,Chuche, Josselin
, p. 92 - 93 (1980)
Pyrolysis of the enamino esters (1a, b) leads to the (allylimino)keten intermediates (2a, b) which by cycloaddition and 1,5-sigmatropic hydrogen shift are converted into the new bicyclic heterocycles (3a, b), respectively, and, via the azatrienals (5), to
Design and development of FGF-23 antagonists: Definition of the pharmacophore and initial structure-activity relationships probed by synthetic analogues
Downs, Ryan P.,Xiao, Zhousheng,Ikedionwu, Munachi O.,Cleveland, Jacob W.,Lin Chin, Ai,Cafferty, Abigail E.,Darryl Quarles,Carrick, Jesse D.
supporting information, (2020/11/30)
Hereditary hypophosphatemic disorders, TIO, and CKD conditions are believed to be influenced by an excess of Fibroblast Growth Factor-23 (FGF-23) which activates a binary renal FGFRs / α-Klotho complex to regulate homeostatic metabolism of phosphate and vitamin D. Adaptive FGF-23 responses from CKD patients with excess FGF-23 frequently lead to increased mortality from cardiovascular disease. A reversibly binding small molecule therapeutic has yet to emerge from research and development in this area. Current outcomes described in this work highlight efforts related to lead identification and modification using organic synthesis of strategic analogues to probe structure-activity relationships and preliminarily define the pharmacophore of a computationally derived hit obtained from virtual high-throughput screening. Synthetic strategies for the initial hit and analogue preparation, as well as preliminary cellular in vitro assay results highlighting sub micromolar inhibition of the FGF-23 signaling sequence at a concentration well below cytotoxicity are reported herein.
Tandem vinyl radical Minisci-type annulation on pyridines: one-pot expeditious access to azaindenones
Xia, Dong,Duan, Xin-Fang
supporting information, p. 13570 - 13573 (2021/12/23)
A new regiospecific alkylative/alkenylative cascade annulation of pyridines has been achieved whilst the corresponding classic Minisci alkylative annulation failed. This protocol provides a novel and expeditious access to azaindenones and related compoundsviacross-dehydrogenative coupling with the long-standing problem of C2/C4 regioselectivity of pyridines being well addressed.
New α-Hydroxy-1,2,3-triazoles and 9H-Fluorenes-1,2,3-triazoles: H Synthesis and Evaluation as Glycine Transporter 1 Inhibitors
Buarque, Camilla D.,Guimar?es, Marilia Z.,López?Corcuera, Beatriz,Neto, Jo?o Gon?alves,No?l, Fran?ois,Silva, Rafaela R.,da Silva, Veronica D.
, p. 1258 - 1269 (2020/10/14)
Two series of new compounds containing 1,2,3-triazole moiety were designed as putative GlyT1 inhibitors aiming the discovery of new hits with activity in cognitive disorders. 1,4-Disubstituted α-hydroxy-1,2,3-triazoles were obtained as racemates in moderate to good yields by the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction (click chemistry) as the key step between propargyl alcohols and aryl azides, previously prepared from anilines or boronic acids. Benzo[c]chromene-triazoles were planned to be obtained by palladium-catalyzed C?H activation using [bis(trifluoroacetoxy)iodobenzene] (PhI(TFA)2) of some α-hydroxy-1,2,3-triazoles, since benzo[c]chromenes are also privileged groups with several biological activities, including to the central nervous system. Unexpectedly, 9H-fluorenes-1,2,3-triazoles, instead of benzo[c]chromenetriazoles, were obtained by Friedel-Crafts alkylation reaction. The two series of compounds were tested for inhibition of the glycine transporter (rat GlyT1 isoform) but only the α-hydroxy-1,2,3-triazole 9b was active (half maximal inhibitory concentration (IC50) = 8.0 μM).
FIBROBLAST GROWTH FACTOR 23 ANTAGONISTS AND RELATED COMPOSITIONS AND METHODS
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Page/Page column 25-26; 33, (2019/05/15)
This disclosure relates to small molecule inhibitors of Fibroblast growth factor 23 (FGF-23) and related compositions and methods of treatment.
Hypervalent Iodonium Alkynyl Triflate Generated Phenylcyanocarbene and Its Reactivity with Aromatic Systems
Al-Huniti, Mohammed H.,Sullivan, Zachary B.,Stanley, Jarrod L.,Carson, James A.,Hyatt, I. F. Dempsey,Hairston, A. Christina,Croatt, Mitchell P.
, p. 11772 - 11780 (2017/11/24)
Phenylcyanocarbene was generated by the reaction of azide with a hypervalent iodonium alkynyl triflate and reacted in situ with 21 different carbocyclic and heterocyclic aromatic compounds. These reactions led to more complex products that frequently underwent subsequent rearrangements. The reactivity was further explored in a mechanistic study to ascertain the chemoselectivity and stereospecificity.
Microwave-assisted syntheses of N-heterocycles using alkenone-, alkynone- and aryl-carbonyl O-phenyl oximes: Formal synthesis of neocryptolepine
Portela-Cubillo, Fernando,Scott, Jackie S.,Walton, John C.
, p. 5558 - 5565 (2008/12/20)
(Chemical Equation Presented) This research aimed to provide a new and "clean" synthetic method that would enable both known and novel N-heterocycles to be prepared efficiently. O-Phenyl oximes were found to be excellent precursors for iminyl radicals with a variety of acceptor side chains. Dihyropyrroles were made in good yields from O-phenyl oximes containing pent-4-ene acceptors. The analogous process with a hex-5-enyl acceptor did not yield a dihydropyridine, probably because the 6-exo-trig ring closure of the iminyl radical was too slow to compete with H-atom abstraction. The iminyl radical from a precursor with a pent-4-yne type side chain underwent ring closure followed by rearrangement to afford a pyrrole derivative. Suitably substituted iminyl radicals ring closed readily onto aromatic acceptors, thus enabling several polycyclic systems to be accessed. Quinolines were made from 3-phenylpropanones via their O-phenyl oximes. Syntheses of phenanthridines starting from 2-formylbiphenyls were particularly efficient, and this approach enabled the natural product trisphaeridine to be made. Starting from 2-phenylnicotinaldehyde derivatives, ring closures of the derived iminyl radicals onto the phenyl rings yielded benzo[h][1,6]naphthyridines. Similarly, ring closure onto a phenyl ring from a benzothiophene-based iminyl yielded a benzo[b-]thieno[2,3-c]quinoline. By way of contrast, iminyl radical ring closure onto pyridine rings was not observed. However, iminyl radicals did cyclize onto indoles, enabling indolopyridines to be prepared. The latter route was exploited in a short formal synthesis of neocryptolepine starting from 2-((1H-indol-3-yl)methyl)cyclohexanone.
