182120-87-2Relevant academic research and scientific papers
Exploring Heteroaromatic Rings as a Replacement for the Labile Amide of Antiplasmodial Pantothenamides
Guan, Jinming,Spry, Christina,Tjhin, Erick T.,Yang, Penghui,Kittikool, Tanakorn,Howieson, Vanessa M.,Ling, Harriet,Starrs, Lora,Duncan, Dustin,Burgio, Gaetan,Saliba, Kevin J.,Auclair, Karine
, p. 4478 - 4497 (2021/05/04)
Malaria-causing Plasmodium parasites are developing resistance to antimalarial drugs, providing the impetus for new antiplasmodials. Although pantothenamides show potent antiplasmodial activity, hydrolysis by pantetheinases/vanins present in blood rapidly inactivates them. We herein report the facile synthesis and biological activity of a small library of pantothenamide analogues in which the labile amide group is replaced with a heteroaromatic ring. Several of these analogues display nanomolar antiplasmodial activity against Plasmodium falciparum and/or Plasmodium knowlesi, and are stable in the presence of pantetheinase. Both a known triazole and a novel isoxazole derivative were further characterized and found to possess high selectivity indices, medium or high Caco-2 permeability, and medium or low microsomal clearance in vitro. Although they fail to suppress Plasmodium berghei proliferation in vivo, the pharmacokinetic and contact time data presented provide a benchmark for the compound profile likely required to achieve antiplasmodial activity in mice and should facilitate lead optimization.
Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2
Labadie, Sharada,Dragovich, Peter S.,Barrett, Kathy,Blair, Wade S.,Bergeron, Philippe,Chang, Christine,Deshmukh, Gauri,Eigenbrot, Charles,Ghilardi, Nico,Gibbons, Paul,Hurley, Christopher A.,Johnson, Adam,Kenny, Jane R.,Kohli, Pawan Bir,Kulagowski, Janusz J.,Liimatta, Marya,Lupardus, Patrick J.,Mendonca, Rohan,Murray, Jeremy M.,Pulk, Rebecca,Shia, Steven,Steffek, Micah,Ubhayakar, Savita,Ultsch, Mark,Van Abbema, Anne,Ward, Stuart,Zak, Mark
, p. 7627 - 7633 (2013/02/21)
Herein we describe our successful efforts in obtaining C-2 substituted imidazo-pyrrolopyridines with improved JAK1 selectivity relative to JAK2 by targeting an amino acid residue that differs between the two isoforms (JAK1: E966; JAK2: D939). Efforts to improve cellular potency by reducing the polarity of the inhibitors are also detailed. The X-ray crystal structure of a representative inhibitor in complex with the JAK1 enzyme is also disclosed.
Oxazole and thiazole combinatorial libraries
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Page/Page column 5; 9; Sheet 2, (2008/06/13)
This invention provides a novel method for synthesizing an ensemble of peptides that allows for the generation of an unlimited number of antibiotic compounds. More specifically, the method comprises utilizes synthetic heterocyclic amino acids containing thaizole and/or oxazole as building blocks in a solid phase combinatorial synthesis to yield natural and unnatural antibiotic compounds.
Synthese natuerlich vorkommender, konformativ eingeschraenkter Oxazol- und Thiazol-haltiger Di- und Tripeptidmimetika
Videnov, Georgi,Kaiser, Dietmar,Kempter, Christoph,Jung, Guenther
, p. 1604 - 1607 (2007/10/03)
Keywords: Aminosaeuren; Heterocyclen; Oxidationen; Peptidmimetica; Synthesemethoden
