The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
Thomas Strassner - One of the best experts on this subject based on the ideXlab platform.
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sky blue triplet emitters with cyclometalated Imidazopyrazine based nhc ligands and aromatic bulky acetylacetonates
Chemistry: A European Journal, 2019Co-Authors: Piermaria Pinter, Johannes Soellner, Thomas StrassnerAbstract:Platinum(II) complexes with an N-heterocyclic carbene and a cyclometalating phenyl ligand (C^C*) are excellent candidates as efficient blue triplet emitters for OLED applications. The electronic and photophysical properties of these complexes can be fine-tuned with the objective to increase the quantum yields and lower the phosphorescence decay times. We found that platinum complexes with an Imidazopyrazine C^C* ligand and bulky acetylacetonates are sky-blue triplet emitters, characterised by an almost unitary quantum yield and short phosphorescence decay times.
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Sky‐Blue Triplet Emitters with Cyclometalated Imidazopyrazine‐Based NHC‐Ligands and Aromatic Bulky Acetylacetonates
Chemistry (Weinheim an der Bergstrasse Germany), 2019Co-Authors: Piermaria Pinter, Johannes Soellner, Thomas StrassnerAbstract:Platinum(II) complexes with an N-heterocyclic carbene and a cyclometalating phenyl ligand (C^C*) are excellent candidates as efficient blue triplet emitters for OLED applications. The electronic and photophysical properties of these complexes can be fine-tuned with the objective to increase the quantum yields and lower the phosphorescence decay times. We found that platinum complexes with an Imidazopyrazine C^C* ligand and bulky acetylacetonates are sky-blue triplet emitters, characterised by an almost unitary quantum yield and short phosphorescence decay times.
Arnab K. Chatterjee - One of the best experts on this subject based on the ideXlab platform.
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Lead optimization of Imidazopyrazines: a new class of antimalarial with activity on Plasmodium liver stages.
ACS medicinal chemistry letters, 2014Co-Authors: Bin Zou, Advait Nagle, Arnab K. Chatterjee, Seh Yong Leong, Liying Jocelyn Tan, Wei Lin Sandra Sim, Mishra Pranab, Prasuna Guntapalli, David C. Tully, Suresh B. LakshminarayanaAbstract:Imidazopyridine 1 was identified from a phenotypic screen against P. falciparum (Pf) blood stages and subsequently optimized for activity on liver-stage schizonts of the rodent parasite P. yoelii (Py) as well as hypnozoites of the simian parasite P. cynomolgi (Pc). We applied these various assays to the cell-based lead optimization of the Imidazopyrazines, exemplified by 3 (KAI407), and show that optimized compounds within the series with improved pharmacokinetic properties achieve causal prophylactic activity in vivo and may have the potential to target the dormant stages of P. vivax malaria.
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Targeting Plasmodium PI(4)K to eliminate malaria
Nature, 2013Co-Authors: Case W. Mcnamara, Marcus C. S. Lee, Chek Shik Lim, Siau Hoi Lim, Jason Roland, Advait Nagle, Oliver Simon, Bryan K. S. Yeung, Arnab K. Chatterjee, Susan L. MccormackAbstract:To eliminate malaria completely it is necessary to cure an individual of all stages in the malaria parasite's life cycle including the symptomatic blood-stage infection and the preceding liver-stage infection (to prevent relapse) and also to block transmission to mosquitoes. Here Elizabeth Winzeler and colleagues identify phosphatidylinositol-4-OH kinase (PI(4)K) as a potential drug target that is essential to fatty acid metabolism in all stages of the Plasmodium parasite. The authors show that a family of compounds with an Imidazopyrazine core, distinct from known antimalarials, inhibits PI(4)K and also inhibits the development of multiple Plasmodium species at each stage of the life cycle. Their analyses reveal that the Imidazopyrazines interact with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4 phosphate and interfering with cell division. The lipid kinase phosphatidylinositol-4-OH kinase (PI(4)K) is identified as a target of the Imidazopyrazines, a new antimalarial compound class that can inhibit several Plasmodium species at each stage of the parasite life cycle; the Imidazopyrazines exert their inhibitory action by interacting with the ATP-binding pocket of PI(4)K. Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of Imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax , and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi . We show that Imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.
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Targeting Plasmodium PI(4)K to eliminate malaria
Nature, 2013Co-Authors: Case W. Mcnamara, Marcus C. S. Lee, Chek Shik Lim, Siau Hoi Lim, Jason Roland, Oliver Simon, Bryan K. S. Yeung, Arnab K. Chatterjee, Susan Mccormack, Micah J. ManaryAbstract:Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of Imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that Imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.
Case W. Mcnamara - One of the best experts on this subject based on the ideXlab platform.
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Targeting Plasmodium PI(4)K to eliminate malaria
Nature, 2013Co-Authors: Case W. Mcnamara, Marcus C. S. Lee, Chek Shik Lim, Siau Hoi Lim, Jason Roland, Advait Nagle, Oliver Simon, Bryan K. S. Yeung, Arnab K. Chatterjee, Susan L. MccormackAbstract:To eliminate malaria completely it is necessary to cure an individual of all stages in the malaria parasite's life cycle including the symptomatic blood-stage infection and the preceding liver-stage infection (to prevent relapse) and also to block transmission to mosquitoes. Here Elizabeth Winzeler and colleagues identify phosphatidylinositol-4-OH kinase (PI(4)K) as a potential drug target that is essential to fatty acid metabolism in all stages of the Plasmodium parasite. The authors show that a family of compounds with an Imidazopyrazine core, distinct from known antimalarials, inhibits PI(4)K and also inhibits the development of multiple Plasmodium species at each stage of the life cycle. Their analyses reveal that the Imidazopyrazines interact with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4 phosphate and interfering with cell division. The lipid kinase phosphatidylinositol-4-OH kinase (PI(4)K) is identified as a target of the Imidazopyrazines, a new antimalarial compound class that can inhibit several Plasmodium species at each stage of the parasite life cycle; the Imidazopyrazines exert their inhibitory action by interacting with the ATP-binding pocket of PI(4)K. Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of Imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax , and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi . We show that Imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.
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Targeting Plasmodium phosphatidylinositol-4 kinase for the treatment, prevention and elimination of malaria
2013Co-Authors: Case W. Mcnamara, Chek Shik Lim, Siau Hoi Lim, Jason Roland, Advait Nagle, Oliver Simon, Bryan K. S. Yeung, Kelli L. Kuhen, Kerstin Gagaring, David PlouffeAbstract:Achieving the goal of malaria elimination is vitally dependent on identifying validated drug targets that are active across all stages of the Plasmodium lifecycle. Here, we identify phosphatidylinositol-4 kinase (PfPI4K) as the target of the Imidazopyrazines, a novel antimalarial compound class that potently inhibits the intracellular development of multiple Plasmodium species at each stage of infection of the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in several rodent malaria models. These compounds are also active against blood-stage field isolates of the major human malaria pathogens, P. falciparum and P. vivax, and inhibit liver stage hypnozoites in the human and simian parasite P. cynomolgi. Evolved resistance, full genome-scanning and genome editing experiments in intra-erythrocytic stages as well as biochemical data, show that Imidazopyrazines exert their potent antimalarial activity through interaction with the ATP-binding pocket of the lipid kinase. Inhibition of PfPI4K, alters the intracellular distribution of phosphatidylinositol-4 phosphate, the PI4K product, and interferes with cytokinesis via a Rab11A-dependent pathway. Collectively, our data define PfPI4K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify antimalarial drugs with an ideal pharmacological profile for the prevention, treatment and elimination of malaria.
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Targeting Plasmodium PI(4)K to eliminate malaria
Nature, 2013Co-Authors: Case W. Mcnamara, Marcus C. S. Lee, Chek Shik Lim, Siau Hoi Lim, Jason Roland, Oliver Simon, Bryan K. S. Yeung, Arnab K. Chatterjee, Susan Mccormack, Micah J. ManaryAbstract:Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of Imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that Imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.
Piermaria Pinter - One of the best experts on this subject based on the ideXlab platform.
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sky blue triplet emitters with cyclometalated Imidazopyrazine based nhc ligands and aromatic bulky acetylacetonates
Chemistry: A European Journal, 2019Co-Authors: Piermaria Pinter, Johannes Soellner, Thomas StrassnerAbstract:Platinum(II) complexes with an N-heterocyclic carbene and a cyclometalating phenyl ligand (C^C*) are excellent candidates as efficient blue triplet emitters for OLED applications. The electronic and photophysical properties of these complexes can be fine-tuned with the objective to increase the quantum yields and lower the phosphorescence decay times. We found that platinum complexes with an Imidazopyrazine C^C* ligand and bulky acetylacetonates are sky-blue triplet emitters, characterised by an almost unitary quantum yield and short phosphorescence decay times.
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Sky‐Blue Triplet Emitters with Cyclometalated Imidazopyrazine‐Based NHC‐Ligands and Aromatic Bulky Acetylacetonates
Chemistry (Weinheim an der Bergstrasse Germany), 2019Co-Authors: Piermaria Pinter, Johannes Soellner, Thomas StrassnerAbstract:Platinum(II) complexes with an N-heterocyclic carbene and a cyclometalating phenyl ligand (C^C*) are excellent candidates as efficient blue triplet emitters for OLED applications. The electronic and photophysical properties of these complexes can be fine-tuned with the objective to increase the quantum yields and lower the phosphorescence decay times. We found that platinum complexes with an Imidazopyrazine C^C* ligand and bulky acetylacetonates are sky-blue triplet emitters, characterised by an almost unitary quantum yield and short phosphorescence decay times.
Huanfeng Jiang - One of the best experts on this subject based on the ideXlab platform.
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copper catalyzed intermolecular oxidative cyclization of halo alkynes synthesis of 2 halo substituted imidazo 1 2 a pyridines imidazo 1 2 a pyrazines and imidazo 1 2 a pyrimidines
Advanced Synthesis & Catalysis, 2013Co-Authors: Wanqing Wu, Huawen Huang, Huanfeng JiangAbstract:An efficient copper-catalyzed method for the synthesis of 2-haloimidazopyridines with aminopyridines and haloalkynes using molecular oxygen as oxidant in a one-pot manner has been developed. In this process, the reaction appears to be very general and suitable for the construction of a variety of 2-halo-substituted imidazopyridines, Imidazopyrazines and imidazopyrimidines. The intermolecular oxidative diamination of haloalkynes was achieved for the first time. Importantly, the mild reaction conditions and the efficient conversion of the alkyl-substituted haloalkynes are great improvements over the existing methods. Moreover, the resultant 2-haloimidazo[1,2-a]pyridines could be efficiently converted to other functionalized imidazopyridine products via substitution, coupling reactions and other transformations, which further indicates potential applications of this method in synthetic and pharmaceutical chemistry.
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Copper‐Catalyzed Intermolecular Oxidative Cyclization of Halo‐ alkynes: Synthesis of 2‐Halo‐substituted Imidazo[1,2‐a]pyridines, Imidazo[1,2‐a]pyrazines and Imidazo[1,2‐a]pyrimidines
Advanced Synthesis & Catalysis, 2013Co-Authors: Yang Gao, Huawen Huang, Meizhou Yin, Huanfeng JiangAbstract:An efficient copper-catalyzed method for the synthesis of 2-haloimidazopyridines with aminopyridines and haloalkynes using molecular oxygen as oxidant in a one-pot manner has been developed. In this process, the reaction appears to be very general and suitable for the construction of a variety of 2-halo-substituted imidazopyridines, Imidazopyrazines and imidazopyrimidines. The intermolecular oxidative diamination of haloalkynes was achieved for the first time. Importantly, the mild reaction conditions and the efficient conversion of the alkyl-substituted haloalkynes are great improvements over the existing methods. Moreover, the resultant 2-haloimidazo[1,2-a]pyridines could be efficiently converted to other functionalized imidazopyridine products via substitution, coupling reactions and other transformations, which further indicates potential applications of this method in synthetic and pharmaceutical chemistry.