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Analyses of synthetic N-acyl dopamine derivatives revealing different structural requirements for their anti-inflammatory and transient-receptor-potential-channel-of-the-vanilloid-receptor-subfamily-subtype-1 (TRPV1)-activating properties

We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for the activation of transient-receptor-potential channels of the vanilloid-receptor subtype 1 (TRPV1) and inhibition of inflammation. The potency of NOD in activating TRPV1 was significantly higher compared with those of...

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Main Authors: Pallavi, Prama (Author) , Pretze, Marc (Author) , Li, Yingchun (Author) , Hofmann, Björn Bastian (Author) , Stamellou, Eleni (Author) , Wängler, Carmen (Author) , Wängler, Björn (Author) , Mörz, Handan (Author) , Binzen, Uta (Author) , Greffrath, Wolfgang (Author) , Treede, Rolf-Detlef (Author) , Krämer, Bernhard (Author) , Hafner, Mathias (Author) , Yard, Benito A. (Author) , Kälsch, Anna-Isabelle (Author)
Format: Article (Journal)
Language:English
Published: March 15, 2018
In: Journal of medicinal chemistry
Year: 2018, Volume: 61, Issue: 7, Pages: 3126-3137
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.8b00156
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/acs.jmedchem.8b00156
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Author Notes:Prama Pallavi, Marc Pretze, Julio Caballero, Yingchun Li, Björn B. Hofmann, Eleni Stamellou, Sarah Klotz, Carmen Wängler, Björn Wängler, Ralf Loesel, Steffen Roth, Bastian Theisinger, Handan Moerz, Uta Binzen, Wolfgang Greffrath, Rolf-Detlef Treede, Martin C. Harmsen, Bernhard K. Krämer, Mathias Hafner, Benito A. Yard, and Anna-Isabelle Kälsch
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Summary:We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for the activation of transient-receptor-potential channels of the vanilloid-receptor subtype 1 (TRPV1) and inhibition of inflammation. The potency of NOD in activating TRPV1 was significantly higher compared with those of variants in which the ortho-dihydroxy groups were acetylated, one of the hydroxy groups was omitted (N-octanoyl tyramine), or the ester functionality consisted of a bulky fatty acid (N-pivaloyl dopamine). Shortening of the amide linker (ΔNOD) slightly increased its potency, which was further increased when the carbonyl and amide groups (ΔNODR) were interchanged. With the exception of ΔNOD, the presence of an intact catechol structure was obligatory for the inhibition of VCAM-1 and the induction of HO-1 expression. Because TRPV1 activation and the inhibition of inflammation by N-acyl dopamines require different structural entities, our findings provide a framework for the rational design of TRPV1 agonists with improved anti-inflammatory properties.
Item Description:Gesehen am 26.08.2020
Physical Description:Online Resource
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.8b00156

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