γ‑Aminobutyric Acid(C) (GABAC) Selective Antagonists Derived from the Bioisosteric Modification of 4‑Aminocyclopent-1-enecarboxylic Acid: Amides and Hydroxamates
Series of compounds were generated via the bioisosteric replacement of the carboxylate of 4-ACPCA (2) with hydroxamate or amide groups. All compounds from this study exhibited increased selectivity for GABAC, the most potent being 4-ACPHA (10a, IC50 = 13 μM) and 4-ACPAM (11a, IC50 = 10 μM). This pro...
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| Veröffentlicht in: | Journal of medicinal chemistry 2013-07, Vol.56 (13), p.5626-5630 |
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| container_title | Journal of medicinal chemistry |
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| creator | Locock, Katherine E. S Yamamoto, Izumi Tran, Priscilla Hanrahan, Jane R Chebib, Mary Johnston, Graham A. R Allan, Robin D |
| description | Series of compounds were generated via the bioisosteric replacement of the carboxylate of 4-ACPCA (2) with hydroxamate or amide groups. All compounds from this study exhibited increased selectivity for GABAC, the most potent being 4-ACPHA (10a, IC50 = 13 μM) and 4-ACPAM (11a, IC50 = 10 μM). This provides evidence that a zwitterionic structure is not essential for GABAC antagonists, rather the emphasis lies in appropriate heteroatoms to participate in hydrogen bonding. |
| doi_str_mv | 10.1021/jm4006548 |
| format | Article |
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R ; Allan, Robin D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-5f97039f25a47a2a79459180cb7a47a1cff1e0ed8b0333a3c55b38bf2fea88693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amides - chemical synthesis</topic><topic>Amides - chemistry</topic><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Binding, Competitive</topic><topic>Chemistry, Pharmaceutical - methods</topic><topic>Cyclopentanes - chemistry</topic><topic>Cyclopentanes - pharmacology</topic><topic>Female</topic><topic>GABA Antagonists - chemistry</topic><topic>GABA Antagonists - pharmacology</topic><topic>Humans</topic><topic>Hydroxamic Acids - chemical synthesis</topic><topic>Hydroxamic Acids - chemistry</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Membrane Potentials - drug effects</topic><topic>Models, Chemical</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Oocytes - drug effects</topic><topic>Oocytes - metabolism</topic><topic>Oocytes - physiology</topic><topic>Patch-Clamp Techniques</topic><topic>Protein Structure, Tertiary</topic><topic>Receptors, GABA - chemistry</topic><topic>Receptors, GABA - genetics</topic><topic>Receptors, GABA - metabolism</topic><topic>Xenopus laevis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Locock, Katherine E. S</creatorcontrib><creatorcontrib>Yamamoto, Izumi</creatorcontrib><creatorcontrib>Tran, Priscilla</creatorcontrib><creatorcontrib>Hanrahan, Jane R</creatorcontrib><creatorcontrib>Chebib, Mary</creatorcontrib><creatorcontrib>Johnston, Graham A. R</creatorcontrib><creatorcontrib>Allan, Robin D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Locock, Katherine E. S</au><au>Yamamoto, Izumi</au><au>Tran, Priscilla</au><au>Hanrahan, Jane R</au><au>Chebib, Mary</au><au>Johnston, Graham A. 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This provides evidence that a zwitterionic structure is not essential for GABAC antagonists, rather the emphasis lies in appropriate heteroatoms to participate in hydrogen bonding.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>23755849</pmid><doi>10.1021/jm4006548</doi><tpages>5</tpages></addata></record> |
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| subjects | Amides - chemical synthesis Amides - chemistry Amides - pharmacology Animals Binding, Competitive Chemistry, Pharmaceutical - methods Cyclopentanes - chemistry Cyclopentanes - pharmacology Female GABA Antagonists - chemistry GABA Antagonists - pharmacology Humans Hydroxamic Acids - chemical synthesis Hydroxamic Acids - chemistry Hydroxamic Acids - pharmacology Membrane Potentials - drug effects Models, Chemical Models, Molecular Molecular Structure Oocytes - drug effects Oocytes - metabolism Oocytes - physiology Patch-Clamp Techniques Protein Structure, Tertiary Receptors, GABA - chemistry Receptors, GABA - genetics Receptors, GABA - metabolism Xenopus laevis |
| title | γ‑Aminobutyric Acid(C) (GABAC) Selective Antagonists Derived from the Bioisosteric Modification of 4‑Aminocyclopent-1-enecarboxylic Acid: Amides and Hydroxamates |
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