Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode. / Kramer, Vasko; Herth, Matthias M; Santini, Martin A; Palner, Mikael; Knudsen, Gitte M; Rösch, Frank.

In: Chemical Biology & Drug Design (Online), Vol. 76, No. 4, 01.10.2010, p. 361-6.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kramer, V, Herth, MM, Santini, MA, Palner, M, Knudsen, GM & Rösch, F 2010, 'Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode', Chemical Biology & Drug Design (Online), vol. 76, no. 4, pp. 361-6. https://doi.org/10.1111/j.1747-0285.2010.01011.x, https://doi.org/10.1111/j.1747-0285.2010.01011.x

APA

Kramer, V., Herth, M. M., Santini, M. A., Palner, M., Knudsen, G. M., & Rösch, F. (2010). Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode. Chemical Biology & Drug Design (Online), 76(4), 361-6. https://doi.org/10.1111/j.1747-0285.2010.01011.x, https://doi.org/10.1111/j.1747-0285.2010.01011.x

Vancouver

Kramer V, Herth MM, Santini MA, Palner M, Knudsen GM, Rösch F. Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode. Chemical Biology & Drug Design (Online). 2010 Oct 1;76(4):361-6. https://doi.org/10.1111/j.1747-0285.2010.01011.x, https://doi.org/10.1111/j.1747-0285.2010.01011.x

Author

Kramer, Vasko ; Herth, Matthias M ; Santini, Martin A ; Palner, Mikael ; Knudsen, Gitte M ; Rösch, Frank. / Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode. In: Chemical Biology & Drug Design (Online). 2010 ; Vol. 76, No. 4. pp. 361-6.

Bibtex

@article{f7ae1ca02c1f4106be6111af0f167a59,
title = "Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode",
abstract = "MH.MZ, MDL 100907, and altanserin are structurally similar 4-benzoyl-piperidine derivatives and are well accommodated to receptor interaction models. We combined structural elements of different high-affinity and selective 5-HT(2A) antagonists, as MH.MZ, altanserin, and SR 46349B, to improve the binding properties of new compounds. Three new derivatives were synthesized with a 4-benzoyl-piperidine moiety as the lead structure. The in vitro affinity of the novel compounds was determined by a [³H]MDL 100907 competition binding assay. The combination of MH.MZ and SR 46349B resulted in a compound (8) with a moderate affinity toward the 5-HT(2A) receptor (K(i) = 57 nm). The remarkably reduced affinity of other compounds (4a), (4b), and (4c) (K(i) = 411, 360 and 356 nm respectively) indicates that MH.MZ can only bind to the 5-HT(2A) receptor with the p-fluorophenylethyl residue in a sterically restricted hydrophobic binding pocket.",
keywords = "Binding, Competitive, Combinatorial Chemistry Techniques, Fluorobenzenes, Hydrophobic and Hydrophilic Interactions, Ketanserin, Ligands, Phenols, Piperidines, Protein Binding, Pyridines, Receptor, Serotonin, 5-HT2A, Serotonin 5-HT2 Receptor Antagonists",
author = "Vasko Kramer and Herth, {Matthias M} and Santini, {Martin A} and Mikael Palner and Knudsen, {Gitte M} and Frank R{\"o}sch",
note = "{\textcopyright} 2010 John Wiley & Sons A/S.",
year = "2010",
month = oct,
day = "1",
doi = "10.1111/j.1747-0285.2010.01011.x",
language = "English",
volume = "76",
pages = "361--6",
journal = "Chemical Biology and Drug Design (Print)",
issn = "1747-0277",
publisher = "Wiley-Blackwell",
number = "4",

}

RIS

TY - JOUR

T1 - Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode

AU - Kramer, Vasko

AU - Herth, Matthias M

AU - Santini, Martin A

AU - Palner, Mikael

AU - Knudsen, Gitte M

AU - Rösch, Frank

N1 - © 2010 John Wiley & Sons A/S.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - MH.MZ, MDL 100907, and altanserin are structurally similar 4-benzoyl-piperidine derivatives and are well accommodated to receptor interaction models. We combined structural elements of different high-affinity and selective 5-HT(2A) antagonists, as MH.MZ, altanserin, and SR 46349B, to improve the binding properties of new compounds. Three new derivatives were synthesized with a 4-benzoyl-piperidine moiety as the lead structure. The in vitro affinity of the novel compounds was determined by a [³H]MDL 100907 competition binding assay. The combination of MH.MZ and SR 46349B resulted in a compound (8) with a moderate affinity toward the 5-HT(2A) receptor (K(i) = 57 nm). The remarkably reduced affinity of other compounds (4a), (4b), and (4c) (K(i) = 411, 360 and 356 nm respectively) indicates that MH.MZ can only bind to the 5-HT(2A) receptor with the p-fluorophenylethyl residue in a sterically restricted hydrophobic binding pocket.

AB - MH.MZ, MDL 100907, and altanserin are structurally similar 4-benzoyl-piperidine derivatives and are well accommodated to receptor interaction models. We combined structural elements of different high-affinity and selective 5-HT(2A) antagonists, as MH.MZ, altanserin, and SR 46349B, to improve the binding properties of new compounds. Three new derivatives were synthesized with a 4-benzoyl-piperidine moiety as the lead structure. The in vitro affinity of the novel compounds was determined by a [³H]MDL 100907 competition binding assay. The combination of MH.MZ and SR 46349B resulted in a compound (8) with a moderate affinity toward the 5-HT(2A) receptor (K(i) = 57 nm). The remarkably reduced affinity of other compounds (4a), (4b), and (4c) (K(i) = 411, 360 and 356 nm respectively) indicates that MH.MZ can only bind to the 5-HT(2A) receptor with the p-fluorophenylethyl residue in a sterically restricted hydrophobic binding pocket.

KW - Binding, Competitive

KW - Combinatorial Chemistry Techniques

KW - Fluorobenzenes

KW - Hydrophobic and Hydrophilic Interactions

KW - Ketanserin

KW - Ligands

KW - Phenols

KW - Piperidines

KW - Protein Binding

KW - Pyridines

KW - Receptor, Serotonin, 5-HT2A

KW - Serotonin 5-HT2 Receptor Antagonists

U2 - 10.1111/j.1747-0285.2010.01011.x

DO - 10.1111/j.1747-0285.2010.01011.x

M3 - Journal article

C2 - 20636331

VL - 76

SP - 361

EP - 366

JO - Chemical Biology and Drug Design (Print)

JF - Chemical Biology and Drug Design (Print)

SN - 1747-0277

IS - 4

ER -

ID: 35304393