552295-33-7Relevant academic research and scientific papers
PROTOZOAN PARASITE GROWTH INHIBITORS
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Paragraph 0203; 0225; 0227, (2015/11/10)
Compounds and methods for inhibiting growth of a protozoan parasite. Methods of treating a protozoan parasite infection in a subject by administering a therapeutically effective amount of a compound as disclosed herein. The compounds and methods can be us
Evaluation of aromatic 6-substituted thienopyrimidines as scaffolds against parasites that cause trypanosomiasis, leishmaniasis, and malaria
Woodring, Jennifer L.,Patel, Gautam,Erath, Jessey,Behera, Ranjan,Lee, Patricia J.,Leed, Susan E.,Rodriguez, Ana,Sciotti, Richard J.,Mensa-Wilmot, Kojo,Pollastri, Michael P.
, p. 339 - 346 (2015/03/30)
Target repurposing is a proven method for finding new lead compounds that target Trypanosoma brucei, the causative agent of human African trypanosomiasis. Due to the recent discovery of a lapatinib-derived analog 2 with excellent potency against T. brucei (EC50 = 42 nM) and selectivity over human host cells, we have explored other classes of human tyrosine kinase inhibitor scaffolds in order to expand the range of chemotypes for pursuit. Following library expansion, we found compound 11e to have an EC50 of 84 nM against T. brucei cells while maintaining selectivity over human hepatocytes. In addition, the library was tested against causative agents of Chagas' disease, leishmaniasis, and malaria. Two analogs with sub-micromolar potencies for T. cruzi (4j) and Plasmodium falciparum (11j) were discovered, along with an analog with considerable potency against Leishmania major amastigotes (4e). Besides identifying new and potent protozoan growth inhibitors, these data highlight the value of concurrent screening of a chemical library against different protozoan parasites. This journal is
Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery
Devine, William,Woodring, Jennifer L.,Swaminathan, Uma,Amata, Emanuele,Patel, Gautam,Erath, Jessey,Roncal, Norma E.,Lee, Patricia J.,Leed, Susan E.,Rodriguez, Ana,Mensa-Wilmot, Kojo,Sciotti, Richard J.,Pollastri, Michael P.
, p. 5522 - 5537 (2015/08/03)
Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.
Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors
Stevens, Kirk L.,Alligood, Krystal J.,Alberti, Jennifer G. Badiang,Caferro, Thomas R.,Chamberlain, Stanley D.,Dickerson, Scott H.,Dickson, Hamilton D.,Emerson, Holly K.,Griffin, Robert J.,Hubbard, Robert D.,Keith, Barry R.,Mullin, Robert J.,Petrov, Kimberly G.,Gerding, Roseanne M.,Reno, Michael J.,Rheault, Tara R.,Rusnak, David W.,Sammond, Douglas M.,Smith, Stephon C.,Uehling, David E.,Waterson, Alex G.,Wood, Edgar R.
scheme or table, p. 21 - 26 (2009/04/10)
A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
Thienopyrimidine-based dual EGFR/ErbB-2 inhibitors
Rheault, Tara R.,Caferro, Thomas R.,Dickerson, Scott H.,Donaldson, Kelly H.,Gaul, Michael D.,Goetz, Aaron S.,Mullin, Robert J.,McDonald, Octerloney B.,Petrov, Kimberly G.,Rusnak, David W.,Shewchuk, Lisa M.,Spehar, Glenn M.,Truesdale, Anne T.,Vanderwall, Dana E.,Wood, Edgar R.,Uehling, David E.
scheme or table, p. 817 - 820 (2009/08/15)
Two new series of potent and selective dual EGFR/ErbB-2 kinase inhibitors derived from novel thienopyrimidine cores have been identified. Isomeric thienopyrimidine cores were evaluated as isosteres for a 4-anilinoquinazoline core and several analogs conta
