Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Matthias M Herth
- Vasko Kramer
- Markus Piel
- Mikael Palner
- Patrick J Riss
- Gitte M Knudsen
- Frank Roesch
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000265044500005&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.bmc.2009.03.021
- eISSN
- 1464-3391
- Externe Identifier
- Clarivate Analytics Document Solution ID: 431EQ
- PubMed Identifier: 19329329
- ISSN
- 0968-0896
- Ausgabe der Veröffentlichung
- 8
- Zeitschrift
- BIOORGANIC & MEDICINAL CHEMISTRY
- Schlüsselwörter
- MH.MZ
- 5-HT2A
- MDL 100907
- PET
- F-18-fluorine
- Paginierung
- 2989 - 3002
- Datum der Veröffentlichung
- 2009
- Status
- Published
- Titel
- Synthesis and in vitro affinities of various MDL 100907 derivatives as potential <SUP>18</SUP>F-radioligands for 5-HT<sub>2A</sub> receptor imaging with PET
- Sub types
- Article
- Ausgabe der Zeitschrift
- 17
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Matthias M Herth
- Vasko Kramer
- Markus Piel
- Mikael Palner
- Patrick J Riss
- Gitte M Knudsen
- Frank Rösch
- DOI
- 10.1016/j.bmc.2009.03.021
- ISSN
- 0968-0896
- Ausgabe der Veröffentlichung
- 8
- Zeitschrift
- Bioorganic & Medicinal Chemistry
- Sprache
- en
- Paginierung
- 2989 - 3002
- Datum der Veröffentlichung
- 2009
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.bmc.2009.03.021
- Datum der Datenerfassung
- 2019
- Titel
- Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET
- Ausgabe der Zeitschrift
- 17
Data source: Crossref
- 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.
- Addresses
- Institute of Nuclear Chemistry Johannes Gutenberg-University Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany. herthm@uni-mainz.de
- Autoren
- Matthias M Herth
- Vasko Kramer
- Markus Piel
- Mikael Palner
- Patrick J Riss
- Gitte M Knudsen
- Frank Rösch
- DOI
- 10.1016/j.bmc.2009.03.021
- eISSN
- 1464-3391
- Externe Identifier
- PubMed Identifier: 19329329
- Open access
- false
- ISSN
- 0968-0896
- Ausgabe der Veröffentlichung
- 8
- Zeitschrift
- Bioorganic & medicinal chemistry
- Schlüsselwörter
- NIH 3T3 Cells
- Animals
- Humans
- Mice
- Rats
- Fluorine Radioisotopes
- Fluorobenzenes
- Piperidines
- Receptor, Serotonin, 5-HT2A
- Radiopharmaceuticals
- Ligands
- Positron-Emission Tomography
- Radioligand Assay
- Binding, Competitive
- Structure-Activity Relationship
- Kinetics
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2009
- Paginierung
- 2989 - 3002
- Datum der Veröffentlichung
- 2009
- Status
- Published
- Datum der Datenerfassung
- 2009
- Titel
- Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 17
Data source: Europe PubMed Central
- 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.
- Date of acceptance
- 2009
- Autoren
- Matthias M Herth
- Vasko Kramer
- Markus Piel
- Mikael Palner
- Patrick J Riss
- Gitte M Knudsen
- Frank Rösch
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/19329329
- DOI
- 10.1016/j.bmc.2009.03.021
- eISSN
- 1464-3391
- Ausgabe der Veröffentlichung
- 8
- Zeitschrift
- Bioorg Med Chem
- Schlüsselwörter
- Animals
- Binding, Competitive
- Fluorine Radioisotopes
- Fluorobenzenes
- Humans
- Kinetics
- Ligands
- Mice
- NIH 3T3 Cells
- Piperidines
- Positron-Emission Tomography
- Radioligand Assay
- Radiopharmaceuticals
- Rats
- Receptor, Serotonin, 5-HT2A
- Structure-Activity Relationship
- Sprache
- eng
- Country
- England
- Paginierung
- 2989 - 3002
- PII
- S0968-0896(09)00261-2
- Datum der Veröffentlichung
- 2009
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2009
- Titel
- Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 17
Data source: PubMed
- Autoren
- Matthias M Herth
- Vasko Kramer
- Markus Piel
- Mikael Palner
- Patrick J Riss
- Gitte M Knudsen
- Frank Rösch
- Zeitschrift
- Bioorganic & medicinal chemistry
- Artikelnummer
- 8
- Paginierung
- 2989 - 3002
- Datum der Veröffentlichung
- 2009
- Herausgeber
- Pergamon
- Datum der Datenerfassung
- 2021
- Titel
- Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET
- Sub types
- article
- Ausgabe der Zeitschrift
- 17
Data source: Manual
- Beziehungen:
- Property of