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Synthesis and appli...
Synthesis and application of a bromomethyl substituted scaffold to be used for efficient optimization of anti-virulence activity
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- Chorell, Erik (author)
- Umeå universitet,Kemiska institutionen
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- Bengtsson, Christoffer (author)
- Umeå universitet,Kemiska institutionen
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- Sainte-Luce Banchelin, Thomas (author)
- Umeå universitet,Kemiska institutionen
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- Das, Pralay (author)
- Umeå universitet,Kemiska institutionen
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- Uvell, Hanna (author)
- Umeå universitet,Kemiska institutionen
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- Sinha, Arun K (author)
- Umeå universitet,Kemiska institutionen
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- Pinkner, Jerome S (author)
- Department of Molecular Microbiology, Washington University, School of Medicine, St. Louis, Missouri 63110, USA
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- Hultgren, Scott J (author)
- Department of Molecular Microbiology, Washington University, School of Medicine, St. Louis, Missouri 63110, USA
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- Almqvist, Fredrik (author)
- Umeå universitet,Kemiska institutionen
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(creator_code:org_t)
- Elsevier Masson SAS, 2011
- 2011
- English.
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In: European Journal of Medicinal Chemistry. - : Elsevier Masson SAS. - 0223-5234 .- 1768-3254. ; 46:4, s. 1103-1116
- Related links:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Pilicides are a class of compounds that attenuate virulence in Gram negative bacteria by blocking the chaperone/usher pathway in Escherichia coli. It has also been shown that compounds derived from the peptidomimetic scaffold that the pilicides are based on can prevent both Aβ aggregation and curli formation. To facilitate optimizations towards the different targets, a new synthetic platform has been developed that enables fast and simple introduction of various substituents in position C-7 on the peptidomimetic scaffold. Importantly, this strategy also enables introduction of previously unattainable heteroatoms in this position. Pivotal to the synthetic strategy is the synthesis of a C-7 bromomethyl substituted derivative of the ring-fused dihydrothiazolo 2-pyridone pilicide scaffold. From this versatile and reactive intermediate various heteroatom-linked substituents could be introduced on the scaffold including amines, ethers, amides and sulfonamides. In addition, carbon-carbon bonds could be introduced to the sp(3)-hybridized bromomethyl substituted scaffold by Suzuki-Miyaura cross couplings. Evaluation of the 24 C-7 substituted compounds in whole-bacterial assays provided important structure-activity data and resulted in the identification of a number of new pilicides with activity as good or better than those developed previously.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
- NATURVETENSKAP -- Kemi -- Oorganisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Inorganic Chemistry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Keyword
- Pilicide
- Anti-virulence
- 2-Pyridone
- peptidomimetic
- Infectious diseases
- Infektionssjukdomar
- Organic chemistry
- Organisk kemi
- Bio-inorganic chemistry
- Bio-oorganisk kemi
- Pharmaceutical chemistry
- Läkemedelskemi
- Organic synthesis
- Organisk syntes
- Biorganic Chemistry
- bioorganisk kemi
- Infectious Diseases
- infektionssjukdomar
- computational linguistics
- datorlingvistik
- organisk kemi
- Organic Chemistry
Publication and Content Type
- ref (subject category)
- art (subject category)
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