Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres

Douglas J. Sheffler; Michael T. Nedelovych; Richard Williams; Stephen C. Turner; Brittany B. Duerk; Megan R. Robbins; Sataya B. Jadhav; Colleen M. Niswender; Carrie K. Jones; P. Jeffrey Conn; R. Nathan Daniels; Craig W. Lindsley

doi:10.1016/j.bmcl.2014.01.011

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres

Douglas J. Sheffler, Michael T. Nedelovych, Richard Williams, Stephen C. Turner, Brittany B. Duerk, Megan R. Robbins, Sataya B. Jadhav, Colleen M. Niswender, Carrie K. Jones, P. Jeffrey Conn, R. Nathan Daniels, Craig W. Lindsley

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

8 Citations (Scopus)

Abstract

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series, e.g. I, displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was obsd., within this novel series and a no. of other piperidine bioisosteric cores.

Original language	English
Pages (from-to)	1062-1066
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	4
Early online date	13 Jan 2014
DOIs	https://doi.org/10.1016/j.bmcl.2014.01.011
Publication status	Published - 15 Feb 2014

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10.1016/j.bmcl.2014.01.011

http://www.sciencedirect.com/science/article/pii/S0960894X14000304#

8 Citations
1 Comment/debate

Corrigendum to “Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres” [Bioorg. Med. Chem. Lett. 24 (2014) 1062–1066]
Sheffler, D. J., Nedelcovych, M. T., Williams, R., Turner, S. C., Duerk, B. B., Robbins, M. R., Jadhav, S. B., Niswender, C. M., Jones, C. K., Jeffrey Conn, P., Nathan Daniels, R. & Lindsley, C. W., 24 Mar 2017, In: Bioorganic and Medicinal Chemistry Letters. 27, 9, p. 2079 1 p.
Research output: Contribution to journal › Comment/debate › peer-review

Cite this

Sheffler, D. J., Nedelovych, M. T., Williams, R., Turner, S. C., Duerk, B. B., Robbins, M. R., Jadhav, S. B., Niswender, C. M., Jones, C. K., Conn, P. J., Daniels, R. N., & Lindsley, C. W. (2014). Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres. Bioorganic and Medicinal Chemistry Letters, 24(4), 1062-1066. https://doi.org/10.1016/j.bmcl.2014.01.011

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title = "Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres",

abstract = "This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series, e.g. I, displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was obsd., within this novel series and a no. of other piperidine bioisosteric cores. ",

author = "Sheffler, {Douglas J.} and Nedelovych, {Michael T.} and Richard Williams and Turner, {Stephen C.} and Duerk, {Brittany B.} and Robbins, {Megan R.} and Jadhav, {Sataya B.} and Niswender, {Colleen M.} and Jones, {Carrie K.} and Conn, {P. Jeffrey} and Daniels, {R. Nathan} and Lindsley, {Craig W.}",

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Sheffler, DJ, Nedelovych, MT, Williams, R, Turner, SC, Duerk, BB, Robbins, MR, Jadhav, SB, Niswender, CM, Jones, CK, Conn, PJ, Daniels, RN & Lindsley, CW 2014, 'Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres', Bioorganic and Medicinal Chemistry Letters, vol. 24, no. 4, pp. 1062-1066. https://doi.org/10.1016/j.bmcl.2014.01.011

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AU - Sheffler, Douglas J.

AU - Nedelovych, Michael T.

AU - Williams, Richard

AU - Turner, Stephen C.

AU - Duerk, Brittany B.

AU - Robbins, Megan R.

AU - Jadhav, Sataya B.

AU - Niswender, Colleen M.

AU - Jones, Carrie K.

AU - Conn, P. Jeffrey

AU - Daniels, R. Nathan

AU - Lindsley, Craig W.

PY - 2014/2/15

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N2 - This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series, e.g. I, displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was obsd., within this novel series and a no. of other piperidine bioisosteric cores.

AB - This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series, e.g. I, displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was obsd., within this novel series and a no. of other piperidine bioisosteric cores.

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DO - 10.1016/j.bmcl.2014.01.011

M3 - Article

SN - 0960-894X

VL - 24

SP - 1062

EP - 1066

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres

Abstract

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Research output

Corrigendum to “Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres” [Bioorg. Med. Chem. Lett. 24 (2014) 1062–1066]

Cite this