Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors

Kenneth J. Wilson; Carl R. Illig; Jinsheng Chen; Mark J. Wall; Shelley K. Ballentine; Renee L. Desjarlais; Yanmin Chen; Carsten Schubert; Robert Donatelli; Ioanna Petrounia; Carl S. Crysler; Christopher J. Molloy; Margery A. Chaikin; Carl L. Manthey; Mark R. Player; Bruce E. Tomczuk; Sanath K. Meegalla

doi:10.1016/j.bmcl.2010.05.013

Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors

Kenneth J. Wilson, Carl R. Illig, Jinsheng Chen, Mark J. Wall, Shelley K. Ballentine, Renee L. Desjarlais, Yanmin Chen, Carsten Schubert, Robert Donatelli, Ioanna Petrounia, Carl S. Crysler, Christopher J. Molloy, Margery A. Chaikin, Carl L. Manthey, Mark R. Player, Bruce E. Tomczuk, Sanath K. Meegalla

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

10 Scopus citations

Abstract

During efforts to improve the bioavailability of FMS kinase inhibitors 1 and 2, a series of saturated and aromatic 4-heterocycles of reduced basicity were prepared and evaluated in an attempt to also improve the cardiovascular safety profile over lead arylamide 1, which possessed ion channel activity. The resultant compounds retained excellent potency and exhibited diminished ion channel activity.

Original language	American English
Pages (from-to)	3925-3929
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2010.05.013
State	Published - 2010
Externally published	Yes

ASJC Scopus subject areas

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

Keywords

Anti-inflammatory activity
CSF-1R
Colony stimulating factor-1
FMS
M-CSF
Macrophages

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10.1016/j.bmcl.2010.05.013

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Wilson, K. J., Illig, C. R., Chen, J., Wall, M. J., Ballentine, S. K., Desjarlais, R. L., Chen, Y., Schubert, C., Donatelli, R., Petrounia, I., Crysler, C. S., Molloy, C. J., Chaikin, M. A., Manthey, C. L., Player, M. R., Tomczuk, B. E., & Meegalla, S. K. (2010). Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors. Bioorganic and Medicinal Chemistry Letters, 20(13), 3925-3929. https://doi.org/10.1016/j.bmcl.2010.05.013

@article{188acd2938e9461188e45c2b7f3e3b0b,

title = "Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors",

abstract = "During efforts to improve the bioavailability of FMS kinase inhibitors 1 and 2, a series of saturated and aromatic 4-heterocycles of reduced basicity were prepared and evaluated in an attempt to also improve the cardiovascular safety profile over lead arylamide 1, which possessed ion channel activity. The resultant compounds retained excellent potency and exhibited diminished ion channel activity.",

keywords = "Anti-inflammatory activity, CSF-1R, Colony stimulating factor-1, FMS, M-CSF, Macrophages",

author = "Wilson, {Kenneth J.} and Illig, {Carl R.} and Jinsheng Chen and Wall, {Mark J.} and Ballentine, {Shelley K.} and Desjarlais, {Renee L.} and Yanmin Chen and Carsten Schubert and Robert Donatelli and Ioanna Petrounia and Crysler, {Carl S.} and Molloy, {Christopher J.} and Chaikin, {Margery A.} and Manthey, {Carl L.} and Player, {Mark R.} and Tomczuk, {Bruce E.} and Meegalla, {Sanath K.}",

year = "2010",

doi = "10.1016/j.bmcl.2010.05.013",

language = "American English",

volume = "20",

pages = "3925--3929",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "13",

}

Wilson, KJ, Illig, CR, Chen, J, Wall, MJ, Ballentine, SK, Desjarlais, RL, Chen, Y, Schubert, C, Donatelli, R, Petrounia, I, Crysler, CS, Molloy, CJ, Chaikin, MA, Manthey, CL, Player, MR, Tomczuk, BE & Meegalla, SK 2010, 'Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 13, pp. 3925-3929. https://doi.org/10.1016/j.bmcl.2010.05.013

TY - JOUR

T1 - Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors

AU - Wilson, Kenneth J.

AU - Illig, Carl R.

AU - Chen, Jinsheng

AU - Wall, Mark J.

AU - Ballentine, Shelley K.

AU - Desjarlais, Renee L.

AU - Chen, Yanmin

AU - Schubert, Carsten

AU - Donatelli, Robert

AU - Petrounia, Ioanna

AU - Crysler, Carl S.

AU - Molloy, Christopher J.

AU - Chaikin, Margery A.

AU - Manthey, Carl L.

AU - Player, Mark R.

AU - Tomczuk, Bruce E.

AU - Meegalla, Sanath K.

PY - 2010

Y1 - 2010

N2 - During efforts to improve the bioavailability of FMS kinase inhibitors 1 and 2, a series of saturated and aromatic 4-heterocycles of reduced basicity were prepared and evaluated in an attempt to also improve the cardiovascular safety profile over lead arylamide 1, which possessed ion channel activity. The resultant compounds retained excellent potency and exhibited diminished ion channel activity.

AB - During efforts to improve the bioavailability of FMS kinase inhibitors 1 and 2, a series of saturated and aromatic 4-heterocycles of reduced basicity were prepared and evaluated in an attempt to also improve the cardiovascular safety profile over lead arylamide 1, which possessed ion channel activity. The resultant compounds retained excellent potency and exhibited diminished ion channel activity.

KW - Anti-inflammatory activity

KW - CSF-1R

KW - Colony stimulating factor-1

KW - FMS

KW - M-CSF

KW - Macrophages

UR - http://www.scopus.com/inward/record.url?scp=77954313375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954313375&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2010.05.013

DO - 10.1016/j.bmcl.2010.05.013

M3 - Article

C2 - 20570147

SN - 0960-894X

VL - 20

SP - 3925

EP - 3929

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 13

ER -

Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors

Abstract

ASJC Scopus subject areas

Keywords

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