Azepinone as a conformational constraint in the design of κ-opioid receptor agonists

Paul A. Tuthill; Pamela R. Seida; William Barker; Joel A. Cassel; Serge Belanger; Robert N. DeHaven; Michael Koblish; Susan L. Gottshall; Patrick J. Little; Diane L. DeHaven-Hudkins; Roland E. Dolle

doi:10.1016/j.bmcl.2004.08.041

Azepinone as a conformational constraint in the design of κ-opioid receptor agonists

Paul A. Tuthill, Pamela R. Seida, William Barker, Joel A. Cassel, Serge Belanger, Robert N. DeHaven, Michael Koblish, Susan L. Gottshall, Patrick J. Little, Diane L. DeHaven-Hudkins, Roland E. Dolle

Center for Drug Discovery

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

20 Scopus citations

Abstract

A new class of κ-opioid receptor agonists is described. The design of these agents was based upon energy minimization and structural overlay studies of the generic azepin-2-one structure 3 with the crystal structure of arylacetamide κ agonist 1, ICI 199441. The most active compound identified was ligand 4a (K _i = 0.34 nM), which demonstrated potent antinociceptive activity after oral administration in rodents.

Original language	English
Pages (from-to)	5693-5697
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2004.08.041
State	Published - Nov 15 2004

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Tuthill, P. A., Seida, P. R., Barker, W., Cassel, J. A., Belanger, S., DeHaven, R. N., Koblish, M., Gottshall, S. L., Little, P. J., DeHaven-Hudkins, D. L., & Dolle, R. E. (2004). Azepinone as a conformational constraint in the design of κ-opioid receptor agonists. Bioorganic and Medicinal Chemistry Letters, 14(22), 5693-5697. https://doi.org/10.1016/j.bmcl.2004.08.041

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abstract = "A new class of κ-opioid receptor agonists is described. The design of these agents was based upon energy minimization and structural overlay studies of the generic azepin-2-one structure 3 with the crystal structure of arylacetamide κ agonist 1, ICI 199441. The most active compound identified was ligand 4a (K i = 0.34 nM), which demonstrated potent antinociceptive activity after oral administration in rodents.",

author = "Tuthill, {Paul A.} and Seida, {Pamela R.} and William Barker and Cassel, {Joel A.} and Serge Belanger and DeHaven, {Robert N.} and Michael Koblish and Gottshall, {Susan L.} and Little, {Patrick J.} and DeHaven-Hudkins, {Diane L.} and Dolle, {Roland E.}",

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doi = "10.1016/j.bmcl.2004.08.041",

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AU - Tuthill, Paul A.

AU - Seida, Pamela R.

AU - Barker, William

AU - Cassel, Joel A.

AU - Belanger, Serge

AU - DeHaven, Robert N.

AU - Koblish, Michael

AU - Gottshall, Susan L.

AU - Little, Patrick J.

AU - DeHaven-Hudkins, Diane L.

AU - Dolle, Roland E.

PY - 2004/11/15

Y1 - 2004/11/15

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AB - A new class of κ-opioid receptor agonists is described. The design of these agents was based upon energy minimization and structural overlay studies of the generic azepin-2-one structure 3 with the crystal structure of arylacetamide κ agonist 1, ICI 199441. The most active compound identified was ligand 4a (K i = 0.34 nM), which demonstrated potent antinociceptive activity after oral administration in rodents.

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DO - 10.1016/j.bmcl.2004.08.041

M3 - Article

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AN - SCOPUS:5144224991

SN - 0960-894X

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EP - 5697

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 22

ER -

Azepinone as a conformational constraint in the design of κ-opioid receptor agonists

Abstract

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