2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors

Susan Luehr; Marcelo Vilches-Herrera; Angelica Fierro; Rona R. Ramsay; Dale E. Edmondson; Miguel Reyes-Parada; Bruce K. Cassels; Patricio Iturriaga-Vasquez

doi:10.1016/j.bmc.2010.01.029

2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors

Susan Luehr, Marcelo Vilches-Herrera, Angelica Fierro, Rona R. Ramsay, Dale E. Edmondson, Miguel Reyes-Parada, Bruce K. Cassels, Patricio Iturriaga-Vasquez

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

Abstract

2-Arylthiomorpholine and 2-arylthiomorpholin-5-one derivatives, designed as rigid and/or non-basic phenylethylamine analogues, were evaluated as rat and human monoamine oxidase inhibitors. Molecular docking provided insight into the binding mode of these inhibitors and rationalized their different potencies. Making the phenylethylamine scaffold rigid by. xing the amine chain in an extended six-membered ring conformation increased MAO-B (but not MAO-A) inhibitory activity relative to the more flexible alpha-methylated derivative. The presence of a basic nitrogen atom is not a prerequisite in either MAO-A or MAO-B. The best K-i values were in the 10(8) M range, with selectivities towards human MAO-B exceeding 2000-fold. (C) 2010 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	1388-1395
Number of pages	8
Journal	Bioorganic & Medicinal Chemistry
Volume	18
Issue number	4
DOIs	https://doi.org/10.1016/j.bmc.2010.01.029
Publication status	Published - 15 Feb 2010

Keywords

Monoamine oxidase
MAO inhibitors
Arylthiomorpholine derivatives
Amphetamine
Human and rat MAO
Docking
MAO-B
BIOLOGICAL-ACTIVITIES
ALZHEIMERS-DISEASE
ANALOGS
INSIGHTS
INACTIVATION
RECOGNITION
SAFINAMIDE
DOCKING

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2010.01.029

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title = "2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors",

abstract = "2-Arylthiomorpholine and 2-arylthiomorpholin-5-one derivatives, designed as rigid and/or non-basic phenylethylamine analogues, were evaluated as rat and human monoamine oxidase inhibitors. Molecular docking provided insight into the binding mode of these inhibitors and rationalized their different potencies. Making the phenylethylamine scaffold rigid by. xing the amine chain in an extended six-membered ring conformation increased MAO-B (but not MAO-A) inhibitory activity relative to the more flexible alpha-methylated derivative. The presence of a basic nitrogen atom is not a prerequisite in either MAO-A or MAO-B. The best K-i values were in the 10(8) M range, with selectivities towards human MAO-B exceeding 2000-fold. (C) 2010 Elsevier Ltd. All rights reserved.",

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author = "Susan Luehr and Marcelo Vilches-Herrera and Angelica Fierro and Ramsay, {Rona R.} and Edmondson, {Dale E.} and Miguel Reyes-Parada and Cassels, {Bruce K.} and Patricio Iturriaga-Vasquez",

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doi = "10.1016/j.bmc.2010.01.029",

language = "English",

volume = "18",

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publisher = "Elsevier",

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TY - JOUR

T1 - 2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors

AU - Luehr, Susan

AU - Vilches-Herrera, Marcelo

AU - Fierro, Angelica

AU - Ramsay, Rona R.

AU - Edmondson, Dale E.

AU - Reyes-Parada, Miguel

AU - Cassels, Bruce K.

AU - Iturriaga-Vasquez, Patricio

PY - 2010/2/15

Y1 - 2010/2/15

N2 - 2-Arylthiomorpholine and 2-arylthiomorpholin-5-one derivatives, designed as rigid and/or non-basic phenylethylamine analogues, were evaluated as rat and human monoamine oxidase inhibitors. Molecular docking provided insight into the binding mode of these inhibitors and rationalized their different potencies. Making the phenylethylamine scaffold rigid by. xing the amine chain in an extended six-membered ring conformation increased MAO-B (but not MAO-A) inhibitory activity relative to the more flexible alpha-methylated derivative. The presence of a basic nitrogen atom is not a prerequisite in either MAO-A or MAO-B. The best K-i values were in the 10(8) M range, with selectivities towards human MAO-B exceeding 2000-fold. (C) 2010 Elsevier Ltd. All rights reserved.

AB - 2-Arylthiomorpholine and 2-arylthiomorpholin-5-one derivatives, designed as rigid and/or non-basic phenylethylamine analogues, were evaluated as rat and human monoamine oxidase inhibitors. Molecular docking provided insight into the binding mode of these inhibitors and rationalized their different potencies. Making the phenylethylamine scaffold rigid by. xing the amine chain in an extended six-membered ring conformation increased MAO-B (but not MAO-A) inhibitory activity relative to the more flexible alpha-methylated derivative. The presence of a basic nitrogen atom is not a prerequisite in either MAO-A or MAO-B. The best K-i values were in the 10(8) M range, with selectivities towards human MAO-B exceeding 2000-fold. (C) 2010 Elsevier Ltd. All rights reserved.

KW - Monoamine oxidase

KW - MAO inhibitors

KW - Arylthiomorpholine derivatives

KW - Amphetamine

KW - Human and rat MAO

KW - Docking

KW - MAO-B

KW - BIOLOGICAL-ACTIVITIES

KW - ALZHEIMERS-DISEASE

KW - ANALOGS

KW - INSIGHTS

KW - INACTIVATION

KW - RECOGNITION

KW - SAFINAMIDE

KW - DOCKING

U2 - 10.1016/j.bmc.2010.01.029

DO - 10.1016/j.bmc.2010.01.029

M3 - Article

SN - 0968-0896

VL - 18

SP - 1388

EP - 1395

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 4

ER -

2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors

Abstract

Keywords

UN SDGs

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