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 | |
| State | Published - Jan 15 2013 |
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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
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
}
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 -