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MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 2: achieving activity in vivo through the use of alternative scaffolds
Problems of low solubility, high serum protein binding, and lack of efficacy in vivo in first generation MexAB-OprM specific efflux pump inhibitors were addressed. Through the use of pharmacophore modelling, the key structural elements for pump inhibition were defined. Use of alternative scaffolds u...
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| Published in: | Bioorganic & medicinal chemistry letters 2003-12, Vol.13 (23), p.4205-4208 |
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| Main Authors: | , , , , , , , , , , , , , , |
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| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c420t-c70152f3e05f9f9c24c65ea74c701836170d46cf8b77f0781ddd66396e8bb2113 |
| container_end_page | 4208 |
| container_issue | 23 |
| container_start_page | 4205 |
| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Nakayama, Kiyoshi Ishida, Yohei Ohtsuka, Masami Kawato, Haruko Yoshida, Ken-ichi Yokomizo, Yoshihiro Ohta, Toshiharu Hoshino, Kazuki Otani, Tsuyoshi Kurosaka, Yuichi Yoshida, Kumi Ishida, Hiroko Lee, Ving J. Renau, Thomas E. Watkins, William J. |
| description | Problems of low solubility, high serum protein binding, and lack of efficacy in vivo in first generation MexAB-OprM specific efflux pump inhibitors were addressed. Through the use of pharmacophore modelling, the key structural elements for pump inhibition were defined. Use of alternative scaffolds upon which the key elements were arrayed gave second generation leads with greatly improved physical properties and activity in the potentiation of antibacterial quinolones (levofloxacin and sitafloxacin) versus
Pseudomonas aeruginosa in vivo.
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| doi_str_mv | 10.1016/j.bmcl.2003.07.027 |
| format | article |
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Pseudomonas aeruginosa in vivo.
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Part 2: achieving activity in vivo through the use of alternative scaffolds</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2003-12-01</date><risdate>2003</risdate><volume>13</volume><issue>23</issue><spage>4205</spage><epage>4208</epage><pages>4205-4208</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Problems of low solubility, high serum protein binding, and lack of efficacy in vivo in first generation MexAB-OprM specific efflux pump inhibitors were addressed. Through the use of pharmacophore modelling, the key structural elements for pump inhibition were defined. Use of alternative scaffolds upon which the key elements were arrayed gave second generation leads with greatly improved physical properties and activity in the potentiation of antibacterial quinolones (levofloxacin and sitafloxacin) versus
Pseudomonas aeruginosa in vivo.
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2003-12, Vol.13 (23), p.4205-4208 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | ScienceDirect Freedom Collection |
| subjects | Animals Anti-Bacterial Agents - metabolism Anti-Bacterial Agents - pharmacology Bacterial Outer Membrane Proteins - metabolism Biological Transport, Active - drug effects Carrier Proteins - metabolism Drug Resistance, Microbial Fluoroquinolones - pharmacology Gene Expression Regulation, Bacterial Lactams - metabolism Levofloxacin Membrane Transport Proteins - metabolism Mice Microbial Sensitivity Tests Neutropenia - drug therapy Ofloxacin - pharmacology Protein Binding Pseudomonas aeruginosa - drug effects Pseudomonas aeruginosa - metabolism Rats Sepsis - drug therapy Serum Albumin - metabolism Structure-Activity Relationship |
| title | MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 2: achieving activity in vivo through the use of alternative scaffolds |
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