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

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

doi:10.1016/j.bmcl.2012.11.084

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

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

Entomology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English (US)
Pages (from-to)	417-421
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2012.11.084
State	Published - Jan 15 2013

Keywords

Human liver microsomes stability
Hypertension
Non-urea inhibitors
Soluble epoxide hydrolase

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Organic Chemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry
Biochemistry

Access to Document

10.1016/j.bmcl.2012.11.084

Fingerprint Dive into the research topics of 'Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors'. Together they form a unique fingerprint.

Cite this

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.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 2, 15.01.2013, p. 417-421.

Research output: Contribution to journal › Article › peer-review

@article{dd92b4406d064946989e16a7722d443a,

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

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.",

keywords = "Human liver microsomes stability, Hypertension, Non-urea inhibitors, Soluble epoxide hydrolase",

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

year = "2013",

month = jan,

day = "15",

doi = "10.1016/j.bmcl.2012.11.084",

language = "English (US)",

volume = "23",

pages = "417--421",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "2",

}

TY - JOUR

T1 - Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors

AU - Pecic, Stevan

AU - Pakhomova, Svetlana

AU - Newcomer, Marcia E.

AU - Morisseau, Christophe

AU - Hammock, Bruce D.

AU - Zhu, Zhengxiang

AU - Rinderspacher, Alison

AU - Deng, Shi Xian

PY - 2013/1/15

Y1 - 2013/1/15

N2 - 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.

AB - 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.

KW - Human liver microsomes stability

KW - Hypertension

KW - Non-urea inhibitors

KW - Soluble epoxide hydrolase

UR - http://www.scopus.com/inward/record.url?scp=84871721627&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871721627&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2012.11.084

DO - 10.1016/j.bmcl.2012.11.084

M3 - Article

C2 - 23237835

AN - SCOPUS:84871721627

VL - 23

SP - 417

EP - 421

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this