Peptidyl-urea based inhibitors of soluble epoxide hydrolases

Christophe Morisseau, John W. Newman, Hsing Ju Tsai, Preston A. Baecker, Bruce D. Hammock

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (KI = 15 nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs.

Original languageEnglish (US)
Pages (from-to)5439-5444
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number20
DOIs
StatePublished - Oct 15 2006

Fingerprint

Lead compounds
Epoxide Hydrolases
Biological Availability
Urea
Rats
Dogs
Amino Acids
Pharmaceutical Preparations
Lead

Keywords

  • Cardiovascular diseases
  • Soluble epoxide hydrolase inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Morisseau, C., Newman, J. W., Tsai, H. J., Baecker, P. A., & Hammock, B. D. (2006). Peptidyl-urea based inhibitors of soluble epoxide hydrolases. Bioorganic and Medicinal Chemistry Letters, 16(20), 5439-5444. https://doi.org/10.1016/j.bmcl.2006.07.073

Peptidyl-urea based inhibitors of soluble epoxide hydrolases. / Morisseau, Christophe; Newman, John W.; Tsai, Hsing Ju; Baecker, Preston A.; Hammock, Bruce D.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 20, 15.10.2006, p. 5439-5444.

Research output: Contribution to journalArticle

Morisseau, C, Newman, JW, Tsai, HJ, Baecker, PA & Hammock, BD 2006, 'Peptidyl-urea based inhibitors of soluble epoxide hydrolases', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 20, pp. 5439-5444. https://doi.org/10.1016/j.bmcl.2006.07.073
Morisseau, Christophe ; Newman, John W. ; Tsai, Hsing Ju ; Baecker, Preston A. ; Hammock, Bruce D. / Peptidyl-urea based inhibitors of soluble epoxide hydrolases. In: Bioorganic and Medicinal Chemistry Letters. 2006 ; Vol. 16, No. 20. pp. 5439-5444.
@article{d2326aafcd504728a0250c46739d11ea,
title = "Peptidyl-urea based inhibitors of soluble epoxide hydrolases",
abstract = "We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (KI = 15 nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs.",
keywords = "Cardiovascular diseases, Soluble epoxide hydrolase inhibitors",
author = "Christophe Morisseau and Newman, {John W.} and Tsai, {Hsing Ju} and Baecker, {Preston A.} and Hammock, {Bruce D.}",
year = "2006",
month = "10",
day = "15",
doi = "10.1016/j.bmcl.2006.07.073",
language = "English (US)",
volume = "16",
pages = "5439--5444",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "20",

}

TY - JOUR

T1 - Peptidyl-urea based inhibitors of soluble epoxide hydrolases

AU - Morisseau, Christophe

AU - Newman, John W.

AU - Tsai, Hsing Ju

AU - Baecker, Preston A.

AU - Hammock, Bruce D.

PY - 2006/10/15

Y1 - 2006/10/15

N2 - We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (KI = 15 nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs.

AB - We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (KI = 15 nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs.

KW - Cardiovascular diseases

KW - Soluble epoxide hydrolase inhibitors

UR - http://www.scopus.com/inward/record.url?scp=33748302000&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748302000&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2006.07.073

DO - 10.1016/j.bmcl.2006.07.073

M3 - Article

C2 - 16908134

AN - SCOPUS:33748302000

VL - 16

SP - 5439

EP - 5444

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 20

ER -