Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors

Pecic, Stevan; Pakhomova, Svetlana; Newcomer, Marcia E.; Morisseau, Christophe; Hammock, Bruce D.; Zhu, Zhengxiang; Rinderspacher, Alison; Deng, Shi-Xian

doi:10.1016/j.bmcl.2012.11.084

Title: Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors

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Abstract

A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure–activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.

Authors:

Pecic, Stevan; Pakhomova, Svetlana; Newcomer, Marcia E.; Morisseau, Christophe; Hammock, Bruce D.; Zhu, Zhengxiang; Rinderspacher, Alison; Deng, Shi-Xian ^[1]

Publication Date:: Fri Sep 27 00:00:00 EDT 2013

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: OTHERNIH

OSTI Identifier:: 1094867

Resource Type:: Journal Article

Journal Name:: Bioorg. Med. Chem. Lett.

Additional Journal Information:: Journal Volume: 23; Journal Issue: (2) ; 01, 2013; Journal ID: ISSN 0960-894X

Country of Publication:: United States

Language:: ENGLISH

Citation Formats


                    Pecic, Stevan, Pakhomova, Svetlana, Newcomer, Marcia E., Morisseau, Christophe, Hammock, Bruce D., Zhu, Zhengxiang, Rinderspacher, Alison, Deng, Shi-Xian, LSU), and Columbia). Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.  United States: N. p., 2013. 
        Web.  doi:10.1016/j.bmcl.2012.11.084.

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                    Pecic, Stevan, Pakhomova, Svetlana, Newcomer, Marcia E., Morisseau, Christophe, Hammock, Bruce D., Zhu, Zhengxiang, Rinderspacher, Alison, Deng, Shi-Xian, LSU), & Columbia). Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.  United States.  https://doi.org/10.1016/j.bmcl.2012.11.084

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                    Pecic, Stevan, Pakhomova, Svetlana, Newcomer, Marcia E., Morisseau, Christophe, Hammock, Bruce D., Zhu, Zhengxiang, Rinderspacher, Alison, Deng, Shi-Xian, LSU), and Columbia). 2013.  
        "Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors".  United States.  https://doi.org/10.1016/j.bmcl.2012.11.084.

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@article{osti_1094867,

  title        = {Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors},

  author       = {Pecic, Stevan and Pakhomova, Svetlana and Newcomer, Marcia E. and Morisseau, Christophe and Hammock, Bruce D. and Zhu, Zhengxiang and Rinderspacher, Alison and Deng, Shi-Xian and LSU) and Columbia)},

  abstractNote = {A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure–activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.},

  doi          = {10.1016/j.bmcl.2012.11.084},

  url          = {https://www.osti.gov/biblio/1094867},
  journal      = {Bioorg. Med. Chem. Lett.},

  issn         = {0960-894X},

  number       = (2) ; 01, 2013,

  volume       = 23,

  place        = {United States},

  year         = {Fri Sep 27 00:00:00 EDT 2013},

  month        = {Fri Sep 27 00:00:00 EDT 2013}

}

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https://doi.org/10.1016/j.bmcl.2012.11.084

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