- Cu-Catalyzed Denitrogenative Transannulation of 3-Aminoindazoles to Assemble 1-Aminoisoquinolines and 3-Aminobenzothiophenes
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We disclose a novel Cu-catalyzed denitrogenative transannulation of 3-aminoindazoles to afford diverse functionalized 3-aminobenzothiophenes and 1-aminoisoquinolines, in which denitrogenative transannulation of 3-aminoindazoles is reported for the first t
- Zhou, Yao,Wang, Ya,Lou, Yixian,Song, Qiuling
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p. 8869 - 8873
(2019/09/12)
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- Exploration of 3-methylisoquinoline-4-carbonitriles as protein kinase A inhibitors of Plasmodium falciparum
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A series of isoquinolines have been evaluated in a homology model of Plasmodium falciparum Protein Kinase A (PfPKA) using molecular dynamics. Synthesis of these compounds was then undertaken to investigate their structure-activity relationships. One compo
- Buskes, Melissa J.,Harvey, Katherine L.,Prinz, Boris,Crabb, Brendan S.,Gilson, Paul R.,Wilson, David J.D.,Abbott, Belinda M.
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p. 2389 - 2396
(2016/05/09)
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- Antimalarial activity of novel 4-cyano-3-methylisoquinoline inhibitors against: Plasmodium falciparum: Design, synthesis and biological evaluation
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Central to malaria pathogenesis is the invasion of human red blood cells by Plasmodium falciparum parasites. Following each cycle of intracellular development and replication, parasites activate a cellular program to egress from their current host cell and invade a new one. The orchestration of this process critically relies upon numerous organised phospho-signaling cascades, which are mediated by a number of central kinases. Parasite kinases are emerging as novel antimalarial targets as they have diverged sufficiently from their mammalian counterparts to allow selectable therapeutic action. Parasite protein kinase A (PfPKA) is highly expressed late in the cell cycle of the parasite blood stage and has been shown to phosphorylate a critical invasion protein, Apical Membrane Antigen 1. This enzyme could therefore be a valuable drug target so we have repurposed a substituted 4-cyano-3-methylisoquinoline that has been shown to inhibit rat PKA with the goal of targeting PfPKA. We synthesised a novel series of compounds and, although many potently inhibit the growth of chloroquine sensitive and resistant strains of P. falciparum, they were found to have minimal activity against PfPKA, indicating that they likely have another target important to parasite cytokinesis and invasion.
- Buskes, Melissa J.,Harvey, Katherine L.,Richards, Benjamin J.,Kalhor, Robabeh,Christoff, Rebecca M.,Gardhi, Chamodi K.,Littler, Dene R.,Cope, Elliott D.,Prinz, Boris,Weiss, Greta E.,O'Brien, Nathan J.,Crabb, Brendan S.,Deady, Leslie W.,Gilson, Paul R.,Abbott, Belinda M.
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p. 4617 - 4639
(2016/06/09)
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- Fused isoquinoline systems from reactions of an iminoisocoumarin with nitrogen nucleophiles
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Some reactions of 1-acetylimino-3-methyl-1H-2-benzopyran-4-carbonitrile with nitrogen nucleophiles are reported. This is a versatile intermediate and leads to isoquino[1,2-b]quinazoline (with methyl anthranilate), [1,2,4]triazolo[5,1-a]isoquinoline (with hydrazine), imidazo[2,1-a]isoquinoline (with glycine ethyl ester), benzimidazo[2,1-a]isoquinoline (with o-phenylenediamine) and 1,3,5-triazine (with acetamidine) systems.
- Deady, Leslie W.,Loria, Paul M.,Quazi, Nurul H.
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p. 485 - 488
(2007/10/03)
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- Acetylation of α-cyano-o-tolunitrile: Reinvestigation and convenient synthesis of isoquinolines
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The product from the diacetylation of α-cyano-o-tolunitrile has now been assigned as an isocoumarin derivative. This is readily transformed into various 1-substituted-3-methylisoquinoline-4-carbonitriles by reaction with oxygen, nitrogen, carbon and hydrogen nucleophiles.
- Deady,Quazi
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p. 309 - 320
(2007/10/02)
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