- Design and synthesis of high affinity inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferases directed by ligand efficiency dependent lipophilicity (LELP)
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N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3, 5-trimethyl-1H-pyrazol-4-yl)meth
- Rackham, Mark D.,Brannigan, James A.,Rangachari, Kaveri,Meister, Stephan,Wilkinson, Anthony J.,Holder, Anthony A.,Leatherbarrow, Robin J.,Tate, Edward W.
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supporting information
p. 2773 - 2788
(2014/04/17)
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- Synthesis and structure activity relationship studies of benzothieno[3,2-b]furan derivatives as a novel class of IKKβ inhibitors
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As a novel class of IKKβ inhibitors, a series of tricyclic furan derivatives was designed and synthesized based on the structure of known thiophene IKKβ inhibitors. Among the various fused furan derivatives synthesized, a benzothieno[3,2-b]furan derivative 13a displayed potent inhibitory activity towards IKKβ in enzymatic and cellular assays. The potent inhibitory activity originates from an intramolecular non-bonded S...O interaction which was confirmed by the X-ray structure of JNK3 with 16k. The introduction of further substituents on the core structure led to the discovery of the 6-alkoxy derivatives, which possessed a comparable IKKβ inhibitory activity to 13a and an improved metabolic stability. Among these, appropriately lipophilic compounds 16a, h, i, and 13g (logD>2) were found to possess good oral bioavailability.
- Sugiyama, Hideyuki,Yoshida, Masato,Mori, Kouji,Kawamoto, Tomohiro,Sogabe, Satoshi,Takagi, Terufumi,Oki, Hideyuki,Tanaka, Toshimasa,Kimura, Hiroyuki,Ikeura, Yoshinori
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p. 613 - 624
(2008/02/13)
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- Polycyclic N-heterocyclic compounds. 57 Syntheses of fused furo(or thieno)[2,3-b]pyridine derivatives via smiles rearrangement and cyclization
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An efficient methodology for the synthesis of thieno[2,3-c][2,7]-naphthyridine (6), thieno[2,3-c]isoquinoline (11), furo[2,3-c]isoquinoline (14), [1]benzothieno[3,2-d]thieno[2,3-b]pyridine (21), and [1]benzothieno[3,2-d]furo-[2,3-b]pyridine (26) skeletons from 4-[o-cyanoarylthio(or oxy)]butyronitriles with base via Smiles type rearrangement reaction followed by the cyclization is described.
- Hirota, Takashi,Tomita, Kei-Ichiroh,Sasaki, Kenji,Okuda, Kensuke,Yoshida, Masahiko,Kashino, Setsuo
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p. 741 - 752
(2007/10/03)
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- Analgesic compositions consisting of 2H-benzothieno[3,2-c]pyrazol-3-amine derivatives
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Herein is disclosed 2H-benzothieno[3,2-c]pyrazol-3-amine derivatives, therapeutically acceptable acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions. The derivatives are useful for
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