- Antiparasitic Lead Discovery: Toward Optimization of a Chemotype with Activity Against Multiple Protozoan Parasites
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Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis present a significant burden across the developing world. Existing therapeutics for these protozoal neglected tropical diseases suffer from severe side effects and toxicity. Previously
- Devine, William,Thomas, Sarah M.,Erath, Jessey,Bachovchin, Kelly A.,Lee, Patricia J.,Leed, Susan E.,Rodriguez, Ana,Sciotti, Richard J.,Mensa-Wilmot, Kojo,Pollastri, Michael P.
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p. 350 - 354
(2017/03/17)
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- Discovery of novel potent and highly selective glycogen synthase kinase-3β (GSK3β) inhibitors for Alzheimers Disease: Design, synthesis, and characterization of pyrazines
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Glycogen synthase kinase-3β, also called tau phosphorylating kinase, is a proline-directed serine/threonine kinase which was originally identified due to its role in glycogen metabolism. Active forms of GSK3β localize to pretangle pathology including dystrophic neuritis and neurofibrillary tangles in Alzheimers disease (AD) brain. By using a high throughput screening (HTS) approach to search for new chemical series and cocrystallization of key analogues to guide the optimization and synthesis of our pyrazine series, we have developed highly potent and selective inhibitors showing cellular efficacy and bloo-brain barrier penetrance. The inhibitors are suitable for in vivo efficacy testing and may serve as a new treatment strategy for Alzheimers disease.
- Berg, Stefan,Bergh, Margareta,Hellberg, Sven,Hoegdin, Katharina,Lo-Alfredsson, Yvonne,Soederman, Peter,Von Berg, Stefan,Weigelt, Tatjana,Ormoe, Mats,Xue, Yafeng,Tucker, Julie,Neelissen, Jan,Jerning, Eva,Nilsson, Yvonne,Bhat, Ratan
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supporting information
p. 9107 - 9119,13
(2020/10/15)
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- Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping
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Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling,
- Richardson, Christine M.,Nunns, Claire L.,Williamson, Douglas S.,Parratt, Martin J.,Dokurno, Pawel,Howes, Rob,Borgognoni, Jenifer,Drysdale, Martin J.,Finch, Harry,Hubbard, Roderick E.,Jackson, Philip S.,Kierstan, Peter,Lentzen, Georg,Moore, Jonathan D.,Murray, James B.,Simmonite, Heather,Surgenor, Allan E.,Torrance, Christopher J.
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p. 3880 - 3885
(2008/02/08)
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- New phenylpyridylpiperazine compounds
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A compound selected from those of formula (I): [image] wherein: X represents a C(O) or SO2 group, R1 represents an aryl group or a group NR3R4 wherein R3 and R4 are as defined in the description, R2 represents an alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl-(C1-C6)alkyl group, its isomers, and addition salts thereof, and medicinal products containing the same which are useful in treating conditions treatable by antagonists of type H3 central histamine receptors.
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Page/Page column 4; 5
(2008/06/13)
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