Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists

Rong Jiang; Xinyi Song; Purva Bali; Anthony Smith; Claudia Ruiz Bayona; Li Lin; Michael D. Cameron; Patricia H. McDonald; Paul J. Kenny; Theodore M. Kamenecka

doi:10.1016/j.bmcl.2012.04.122

Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists

Rong Jiang, Xinyi Song, Purva Bali, Anthony Smith, Claudia Ruiz Bayona, Li Lin, Michael D. Cameron, Patricia H. McDonald, Paul J. Kenny, Theodore M. Kamenecka

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

23 Scopus citations

Abstract

A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure-activity relationships (SAR), installation of various groups at the 3-6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.

Original language	English
Pages (from-to)	3890-3894
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2012.04.122
State	Published - 15 Jun 2012
Externally published	Yes

Keywords

Addiction
GPCR
Orexin

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10.1016/j.bmcl.2012.04.122

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title = "Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists",

abstract = "A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure-activity relationships (SAR), installation of various groups at the 3-6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.",

keywords = "Addiction, GPCR, Orexin",

author = "Rong Jiang and Xinyi Song and Purva Bali and Anthony Smith and Bayona, {Claudia Ruiz} and Li Lin and Cameron, {Michael D.} and McDonald, {Patricia H.} and Kenny, {Paul J.} and Kamenecka, {Theodore M.}",

note = "Funding Information: Supported by the National Institute on Drug Abuse (DA023915 to P.J.K.).",

year = "2012",

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language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists

AU - Jiang, Rong

AU - Song, Xinyi

AU - Bali, Purva

AU - Smith, Anthony

AU - Bayona, Claudia Ruiz

AU - Lin, Li

AU - Cameron, Michael D.

AU - McDonald, Patricia H.

AU - Kenny, Paul J.

AU - Kamenecka, Theodore M.

N1 - Funding Information: Supported by the National Institute on Drug Abuse (DA023915 to P.J.K.).

PY - 2012/6/15

Y1 - 2012/6/15

N2 - A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure-activity relationships (SAR), installation of various groups at the 3-6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.

AB - A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure-activity relationships (SAR), installation of various groups at the 3-6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.

KW - Addiction

KW - GPCR

KW - Orexin

UR - http://www.scopus.com/inward/record.url?scp=84861572284&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2012.04.122

DO - 10.1016/j.bmcl.2012.04.122

M3 - Article

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AN - SCOPUS:84861572284

SN - 0960-894X

VL - 22

SP - 3890

EP - 3894

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 12

ER -

Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists

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Keywords

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