31224-43-8Relevant articles and documents
Understanding Cu(ii)-based systems for C(sp3)-H bond functionalization: insights into the synthesis of aza-heterocycles
Camats, Marc,Gómez, Montserrat,Mallet-Ladeira, Sonia,Pla, Daniel,favier, Isabelle
supporting information, p. 219 - 227 (2021/12/29)
Herein we report the synthesis of imidazo[1,5-a]pyridine heterocyclesviaa Cu(ii)-mediated functionalization of α′-C(sp3)-H bonds of pyridinylaldimines and subsequent cyclization. This strategy exploits the inherent directing ability of heteroleptic aldimine and pyridine groups in the substrate yielding the C-H functionalization of α′-methylene groups in a regioselective fashion over distant methyl or methylene groups in β or γ positions. The observed correlation between the nature of the anionic ligands (halidevs.carboxylate) bonded to copper and the chemoselectivity of the C(sp3)-H activation process points to a concerted metalation-deprotonation pathway prior to cyclization to furnish the corresponding imidazo[1,5-a]pyridine derivative. This copper-mediated C(sp3)-H bond functionalization reaction works for a variety of substrates incorporating linear alkyl chains (from 3 to 12 carbon atoms), and good functional group tolerance (aryl, ether and ester groups). Cu-Catalyzed C(sp2)-H cyanation on the imidazole ring can then take place selectively under oxidative conditions.
TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS
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Page/Page column 89-90, (2013/02/28)
Compounds of Formula (I) are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula (I) have the above structure, where the definitions of the variables are provided herein.
Synthesis of some fluorine-containing pyridinealdoximes of potential use for the treatment of organophosphorus nerve-agent poisoning
Timperley, Christopher M.,Banks, R. Eric,Young, Ian M.,Haszeldine, Robert N.
, p. 541 - 547 (2011/09/15)
Fluoroheterocyclic aldoximes were screened as therapeutic agents for the treatment of anticholinesterase poisoning. 2-Fluoropyridine-3- and -6-aldoxime, and 3-fluoropyridine-2- and -4-aldoxime, were synthesised. Attempts to obtain 3,5,6-trifluoropyridine-2,4-bis(aldoxime) and -2-aldoxime, however, proved unsuccessful. Pentafluorobenzaldoxime was prepared by oximation of pentafluorobenzaldehyde. Acid dissociation constants (pKa) and second-order rate constants (kox-) of the fluorinated pyridinealdoximes towards sarin were measured. 2,3,5,6-Tetrafluoropyridine-4- aldoxime had the best profile: its kox- approached that of the therapeutic oxime P2S (310 vs. 120 l mol-1 min-1), but its higher pKa (9.1 vs. 7.8) fell short of the target figure of 8 required for reactivation of inhibited acetylcholinesterase in vivo. N-alkylation of the fluorinated pyridine-aldoximes may reduce their pK a nearer to 8 and enhance their therapeutic potential. Crown Copyright