Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter

Sean R. Bollinger; Darren W. Engers; Elizabeth A. Ennis; Jane Wright; Charles W. Locuson; Craig W. Lindsley; Randy D. Blakely; Corey R. Hopkins

doi:10.1016/j.bmcl.2015.02.058

Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter

Sean R. Bollinger, Darren W. Engers, Elizabeth A. Ennis, Jane Wright, Charles W. Locuson, Craig W. Lindsley, Randy D. Blakely, Corey R. Hopkins

Research output: Contribution to journal › Article

3 Scopus citations

Abstract

The synthesis and SAR of 4-methoxy-3-(piperidin-4-yl) benzamides identified after a high-throughput screen of the MLPCN library is reported. SAR was explored around the 3-piperidine substituent as well as the amide functionality of the reported compounds. Starting from the initial lead compounds, 1-7, iterative medicinal chemistry efforts led to the identification of ML352 (10m). ML352 represents a potent and selective inhibitor of CHT based on a drug-like scaffold.

Original language	English (US)
Pages (from-to)	1757-1760
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2015.02.058
State	Published - Apr 15 2015

Keywords

CHT
Choline transporter
ML352
MLPCN
Structure-activity relationship

ASJC Scopus subject areas

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

Access to Document

10.1016/j.bmcl.2015.02.058

Fingerprint Dive into the research topics of 'Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter'. Together they form a unique fingerprint.

Cite this

Bollinger, S. R., Engers, D. W., Ennis, E. A., Wright, J., Locuson, C. W., Lindsley, C. W., Blakely, R. D., & Hopkins, C. R. (2015). Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter. Bioorganic and Medicinal Chemistry Letters, 25(8), 1757-1760. https://doi.org/10.1016/j.bmcl.2015.02.058

Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter. / Bollinger, Sean R.; Engers, Darren W.; Ennis, Elizabeth A.; Wright, Jane; Locuson, Charles W.; Lindsley, Craig W.; Blakely, Randy D.; Hopkins, Corey R.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 8, 15.04.2015, p. 1757-1760.

Research output: Contribution to journal › Article

Bollinger, SR, Engers, DW, Ennis, EA, Wright, J, Locuson, CW, Lindsley, CW, Blakely, RD & Hopkins, CR 2015, 'Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter', Bioorganic and Medicinal Chemistry Letters, vol. 25, no. 8, pp. 1757-1760. https://doi.org/10.1016/j.bmcl.2015.02.058

Bollinger, Sean R. ; Engers, Darren W. ; Ennis, Elizabeth A. ; Wright, Jane ; Locuson, Charles W. ; Lindsley, Craig W. ; Blakely, Randy D. ; Hopkins, Corey R. / Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter. In: Bioorganic and Medicinal Chemistry Letters. 2015 ; Vol. 25, No. 8. pp. 1757-1760.

@article{1035951179ac4d5dbe1e081095d09bce,

title = "Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter",

abstract = "The synthesis and SAR of 4-methoxy-3-(piperidin-4-yl) benzamides identified after a high-throughput screen of the MLPCN library is reported. SAR was explored around the 3-piperidine substituent as well as the amide functionality of the reported compounds. Starting from the initial lead compounds, 1-7, iterative medicinal chemistry efforts led to the identification of ML352 (10m). ML352 represents a potent and selective inhibitor of CHT based on a drug-like scaffold.",

keywords = "CHT, Choline transporter, ML352, MLPCN, Structure-activity relationship",

author = "Bollinger, {Sean R.} and Engers, {Darren W.} and Ennis, {Elizabeth A.} and Jane Wright and Locuson, {Charles W.} and Lindsley, {Craig W.} and Blakely, {Randy D.} and Hopkins, {Corey R.}",

year = "2015",

month = apr,

day = "15",

doi = "10.1016/j.bmcl.2015.02.058",

language = "English (US)",

volume = "25",

pages = "1757--1760",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "8",

}

TY - JOUR

T1 - Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter

AU - Bollinger, Sean R.

AU - Engers, Darren W.

AU - Ennis, Elizabeth A.

AU - Wright, Jane

AU - Locuson, Charles W.

AU - Lindsley, Craig W.

AU - Blakely, Randy D.

AU - Hopkins, Corey R.

PY - 2015/4/15

Y1 - 2015/4/15

N2 - The synthesis and SAR of 4-methoxy-3-(piperidin-4-yl) benzamides identified after a high-throughput screen of the MLPCN library is reported. SAR was explored around the 3-piperidine substituent as well as the amide functionality of the reported compounds. Starting from the initial lead compounds, 1-7, iterative medicinal chemistry efforts led to the identification of ML352 (10m). ML352 represents a potent and selective inhibitor of CHT based on a drug-like scaffold.

AB - The synthesis and SAR of 4-methoxy-3-(piperidin-4-yl) benzamides identified after a high-throughput screen of the MLPCN library is reported. SAR was explored around the 3-piperidine substituent as well as the amide functionality of the reported compounds. Starting from the initial lead compounds, 1-7, iterative medicinal chemistry efforts led to the identification of ML352 (10m). ML352 represents a potent and selective inhibitor of CHT based on a drug-like scaffold.

KW - CHT

KW - Choline transporter

KW - ML352

KW - MLPCN

KW - Structure-activity relationship

UR - http://www.scopus.com/inward/record.url?scp=84939976006&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939976006&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2015.02.058

DO - 10.1016/j.bmcl.2015.02.058

M3 - Article

C2 - 25801932

AN - SCOPUS:84939976006

VL - 25

SP - 1757

EP - 1760

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 8

ER -