Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET

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Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET. / Herth, Matthias Manfred; Kramer, Vasko; Piel, Markus; Palner, Mikael; Riss, Patrick J.; Knudsen, Gitte M.; Roesch, Frank.

In: Bioorganic & Medicinal Chemistry, Vol. 17, No. 8, 2009, p. 2989-3002.

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

Harvard

Herth, MM, Kramer, V, Piel, M, Palner, M, Riss, PJ, Knudsen, GM & Roesch, F 2009, 'Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET', Bioorganic & Medicinal Chemistry, vol. 17, no. 8, pp. 2989-3002. https://doi.org/10.1016/j.bmc.2009.03.021

APA

Herth, M. M., Kramer, V., Piel, M., Palner, M., Riss, P. J., Knudsen, G. M., & Roesch, F. (2009). Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET. Bioorganic & Medicinal Chemistry, 17(8), 2989-3002. https://doi.org/10.1016/j.bmc.2009.03.021

Vancouver

Herth MM, Kramer V, Piel M, Palner M, Riss PJ, Knudsen GM et al. Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET. Bioorganic & Medicinal Chemistry. 2009;17(8):2989-3002. https://doi.org/10.1016/j.bmc.2009.03.021

Author

Herth, Matthias Manfred ; Kramer, Vasko ; Piel, Markus ; Palner, Mikael ; Riss, Patrick J. ; Knudsen, Gitte M. ; Roesch, Frank. / Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET. In: Bioorganic & Medicinal Chemistry. 2009 ; Vol. 17, No. 8. pp. 2989-3002.

Bibtex

@article{4be27be068a911df928f000ea68e967b,
title = "Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET",
abstract = "Radiolabelled piperidine derivatives such as [(11)C]MDL 100907 and [(18)F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with (18)F-fluorine, were synthesized to improve molecular imaging properties of [(11)C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show K(i)-values in the nanomolar range towards the 5-HT(2A) receptor and insignificant binding to other 5-HT receptor subtypes or receptors. Interestingly, compounds MA-1 (53), MH.MZ (55) and (R)-MH.MZ (56) provide a receptor selectivity profile similar to MDL 100907. These compounds could possibly be preferable antagonistic (18)F-tracers for visualization of the 5-HT(2A) receptor status. Medium affine compounds (VK-1 (32), (51), (52), (54)) were synthesized and have K(i) values between 30 and 120 nM. All promising compounds show logP values between 2 and 3, that is, within the range of those for the established radiotracers altanserin and MDL 100907. The novel compounds MA-1 (53) and (R)-MH.MZ (56) thus appear to be promising high affine and selective tracers of (18)F-labelled analogues for 5-HT(2A) imaging with PET.",
keywords = "MH.MZ, 5-HT2A, MDL 100907, PET, F-18-fluorine",
author = "Herth, {Matthias Manfred} and Vasko Kramer and Markus Piel and Mikael Palner and Riss, {Patrick J.} and Knudsen, {Gitte M.} and Frank Roesch",
year = "2009",
doi = "10.1016/j.bmc.2009.03.021",
language = "English",
volume = "17",
pages = "2989--3002",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",
publisher = "Pergamon Press",
number = "8",

}

RIS

TY - JOUR

T1 - Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET

AU - Herth, Matthias Manfred

AU - Kramer, Vasko

AU - Piel, Markus

AU - Palner, Mikael

AU - Riss, Patrick J.

AU - Knudsen, Gitte M.

AU - Roesch, Frank

PY - 2009

Y1 - 2009

N2 - Radiolabelled piperidine derivatives such as [(11)C]MDL 100907 and [(18)F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with (18)F-fluorine, were synthesized to improve molecular imaging properties of [(11)C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show K(i)-values in the nanomolar range towards the 5-HT(2A) receptor and insignificant binding to other 5-HT receptor subtypes or receptors. Interestingly, compounds MA-1 (53), MH.MZ (55) and (R)-MH.MZ (56) provide a receptor selectivity profile similar to MDL 100907. These compounds could possibly be preferable antagonistic (18)F-tracers for visualization of the 5-HT(2A) receptor status. Medium affine compounds (VK-1 (32), (51), (52), (54)) were synthesized and have K(i) values between 30 and 120 nM. All promising compounds show logP values between 2 and 3, that is, within the range of those for the established radiotracers altanserin and MDL 100907. The novel compounds MA-1 (53) and (R)-MH.MZ (56) thus appear to be promising high affine and selective tracers of (18)F-labelled analogues for 5-HT(2A) imaging with PET.

AB - Radiolabelled piperidine derivatives such as [(11)C]MDL 100907 and [(18)F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with (18)F-fluorine, were synthesized to improve molecular imaging properties of [(11)C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show K(i)-values in the nanomolar range towards the 5-HT(2A) receptor and insignificant binding to other 5-HT receptor subtypes or receptors. Interestingly, compounds MA-1 (53), MH.MZ (55) and (R)-MH.MZ (56) provide a receptor selectivity profile similar to MDL 100907. These compounds could possibly be preferable antagonistic (18)F-tracers for visualization of the 5-HT(2A) receptor status. Medium affine compounds (VK-1 (32), (51), (52), (54)) were synthesized and have K(i) values between 30 and 120 nM. All promising compounds show logP values between 2 and 3, that is, within the range of those for the established radiotracers altanserin and MDL 100907. The novel compounds MA-1 (53) and (R)-MH.MZ (56) thus appear to be promising high affine and selective tracers of (18)F-labelled analogues for 5-HT(2A) imaging with PET.

KW - MH.MZ

KW - 5-HT2A

KW - MDL 100907

KW - PET

KW - F-18-fluorine

U2 - 10.1016/j.bmc.2009.03.021

DO - 10.1016/j.bmc.2009.03.021

M3 - Journal article

C2 - 19329329

VL - 17

SP - 2989

EP - 3002

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 8

ER -

ID: 19977932