Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor: development of synthetic strategies and labeling
Gespeichert in:
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| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Jülich
Graph. Betriebe der Forschungszentrum Jülich GmbH
2007
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | Auch als: Berichte des Forschungszentrums Jülich ; 4252 Zugl.: Köln, Univ., Diss., 2007 |
| Beschreibung: | 89 S. Ill. |
Internformat
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| 245 | 1 | 0 | |a Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor |b development of synthetic strategies and labeling |c von Sebastian Olma |
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Datensatz im Suchindex
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| adam_text | Contents
1 Introduction 1
1.1 Radiopharmaceuticals 1
1.1.1 Therapeutic and diagnostic radiopharmaceuticals 1
1.1.2 SPECT and PET as diagnostic methods 3
1.1.3 The tracer principle 6
1.1.4 Requirements for PET Pharmaceuticals 7
1.2 Production of PET nuclides and synthesis therewith, especially 18F 8
1.2.1 PET nuclides 8
1.2.2 Cyclotron production of radionuclides 11
1.2.3 Chemistry under no carrier added conditions 14
1.2.4 Electrophilic labeling with fluorine 18 15
1.2.5 Nucleophilic labeling with fluorine 18 17
1.2.6 Examples of 18F labeled tracers with application in PET studies 19
1.3 Glutaminergic receptor system 28
1.3.1 Anatomical distribution of glutaminergic neurons 28
1.3.2 Subtypes of the glutamate receptor system 29
1.3.3 AMPA receptors 31
1.3.4 Quinoxalinediones as antagonists of the AMPA receptor 32
1.4 Ureas in pharmaceutical chemistry 33
2 Aims and scope 35
3 Results and Discussion 37
3.1 Radiosynthesis of [18F]fluorophenyl ureas 37
3.1.1 Radiosynthesis of n.c.a. 4 [18F]fluoroaniline 38
3.1.2 Approaches to the preparation of
n.c.a. 4 [18F]fluorophenyl isocyanate 42
3.1.3 N.c.a. 4 [18F]fluorophenyl carbamate 4 nitrophenylester ([18F]3e)
and 4 [18F]fluorophenyl urea derivatives ([18F]4a 4d) 43
3.1.4 Synthesis of carbamate 4 nitrophenylesters and corresponding
4 fluorophenyl urea derivatives as chromatographic standards 46
3.1.5 Application of the developed labeling synthesis to putative AMPA
receptor ligands of the QX family 48
3.2 18F labeling of basic quinoxalinediones 51
3.2.1 Syntheses of CNQX, FNQX and FCQX 51
3.2.2 Radiosyntheses of [18F]FNQX and [18F]FCQX 53
3.3 Pharmacological evaluation of FNQX, [18F]FNQX and FCQX 55
4 Experimental 60
4.1 Chemicals 60
4.2 (Radio )HPLC 60
4.3 Thin layer chromatography 60
4.4 NMR spectroscopy 61
4.5 Melting points 61
4.6 Organic syntheses 61
4.6.1 General method for preparation of alkyl carbamate
nitrophenylesters (3a 3c) 61
4.6.2 General method for preparation of aryl carbamate
nitrophenylesters (3d 3e) 62
4.6.3 General method for preparation of fluorophenyl urea
derivatives (4a 4d) 63
4.6.4 6 Fluoroquinoxaline 2,3(1H,4H) dione 65
4.6.5 6 Fluoro 7 nitroquinoxaline 2,3(1 H,4H) dione (FNQX) 65
4.6.6 2,3 Dioxo 1,2,3,4 tetrahydroquinoxaline 6 carbonitrile 65
4.6.7 7 Nitro 2,3 dioxo 1,2,3,4 tetrahydroquinoxaline
6 carbonitrile (CNQX) 66
4.6.8 2,4 Difluoro 5 nitrobenzonitrile 66
4.6.9 4 Amino 2 fluoro 5 nitrobenzonitrile 67
4.6.10 4,5 Diamino 2 fluorobenzonitrile 67
4.6.11 7 Fluoro 2,3 dioxo 1,2,3,4 tetrahydroquinoxaline
6 carbonitrile (FCQX) 68
4.7 Radiochemical syntheses 69
4.7.1 Production of n.c.a. [18F]fluoride 69
4.7.2 Drying of n.c.a. [18F]fluoride 69
4.7.3 Radiosynthesis of n.c.a. 4 [18F]fluoroaniline ([18F]1) 69
4.7.4 Radiosynthesis of n.c.a. 4 [18F]fluorophenyl ureas ([18F]4a 4d) 70
4.7.5 N.c.a. 6 [18F]Fluoro 7 nitroquinoxaline 2,3(1H,4H) dione
(n.c.a. [18F]FNQX) 71
4.7.6 C.a. 7 [18F]Fluoro 2,3 dioxo 1,2,3,4 tetrahydroquinoxaline
6 carbonitrile (c.a. [18F]FCQX) 71
4.7.7 Determination of the molar activity 72
4.8 Pharmacological evaluation 73
4.8.1 In vitro autoradiography 73
4.8.2 Ex vivo autoradiography 74
5 Summary 75
6 References 78
|
| adam_txt |
Contents
1 Introduction 1
1.1 Radiopharmaceuticals 1
1.1.1 Therapeutic and diagnostic radiopharmaceuticals 1
1.1.2 SPECT and PET as diagnostic methods 3
1.1.3 The tracer principle 6
1.1.4 Requirements for PET Pharmaceuticals 7
1.2 Production of PET nuclides and synthesis therewith, especially 18F 8
1.2.1 PET nuclides 8
1.2.2 Cyclotron production of radionuclides 11
1.2.3 Chemistry under no carrier added conditions 14
1.2.4 Electrophilic labeling with fluorine 18 15
1.2.5 Nucleophilic labeling with fluorine 18 17
1.2.6 Examples of 18F labeled tracers with application in PET studies 19
1.3 Glutaminergic receptor system 28
1.3.1 Anatomical distribution of glutaminergic neurons 28
1.3.2 Subtypes of the glutamate receptor system 29
1.3.3 AMPA receptors 31
1.3.4 Quinoxalinediones as antagonists of the AMPA receptor 32
1.4 Ureas in pharmaceutical chemistry 33
2 Aims and scope 35
3 Results and Discussion 37
3.1 Radiosynthesis of [18F]fluorophenyl ureas 37
3.1.1 Radiosynthesis of n.c.a. 4 [18F]fluoroaniline 38
3.1.2 Approaches to the preparation of
n.c.a. 4 [18F]fluorophenyl isocyanate 42
3.1.3 N.c.a. 4 [18F]fluorophenyl carbamate 4 nitrophenylester ([18F]3e)
and 4 [18F]fluorophenyl urea derivatives ([18F]4a 4d) 43
3.1.4 Synthesis of carbamate 4 nitrophenylesters and corresponding
4 fluorophenyl urea derivatives as chromatographic standards 46
3.1.5 Application of the developed labeling synthesis to putative AMPA
receptor ligands of the QX family 48
3.2 18F labeling of basic quinoxalinediones 51
3.2.1 Syntheses of CNQX, FNQX and FCQX 51
3.2.2 Radiosyntheses of [18F]FNQX and [18F]FCQX 53
3.3 Pharmacological evaluation of FNQX, [18F]FNQX and FCQX 55
4 Experimental 60
4.1 Chemicals 60
4.2 (Radio )HPLC 60
4.3 Thin layer chromatography 60
4.4 NMR spectroscopy 61
4.5 Melting points 61
4.6 Organic syntheses 61
4.6.1 General method for preparation of alkyl carbamate
nitrophenylesters (3a 3c) 61
4.6.2 General method for preparation of aryl carbamate
nitrophenylesters (3d 3e) 62
4.6.3 General method for preparation of fluorophenyl urea
derivatives (4a 4d) 63
4.6.4 6 Fluoroquinoxaline 2,3(1H,4H) dione 65
4.6.5 6 Fluoro 7 nitroquinoxaline 2,3(1 H,4H) dione (FNQX) 65
4.6.6 2,3 Dioxo 1,2,3,4 tetrahydroquinoxaline 6 carbonitrile 65
4.6.7 7 Nitro 2,3 dioxo 1,2,3,4 tetrahydroquinoxaline
6 carbonitrile (CNQX) 66
4.6.8 2,4 Difluoro 5 nitrobenzonitrile 66
4.6.9 4 Amino 2 fluoro 5 nitrobenzonitrile 67
4.6.10 4,5 Diamino 2 fluorobenzonitrile 67
4.6.11 7 Fluoro 2,3 dioxo 1,2,3,4 tetrahydroquinoxaline
6 carbonitrile (FCQX) 68
4.7 Radiochemical syntheses 69
4.7.1 Production of n.c.a. [18F]fluoride 69
4.7.2 Drying of n.c.a. [18F]fluoride 69
4.7.3 Radiosynthesis of n.c.a. 4 [18F]fluoroaniline ([18F]1) 69
4.7.4 Radiosynthesis of n.c.a. 4 [18F]fluorophenyl ureas ([18F]4a 4d) 70
4.7.5 N.c.a. 6 [18F]Fluoro 7 nitroquinoxaline 2,3(1H,4H) dione
(n.c.a. [18F]FNQX) 71
4.7.6 C.a. 7 [18F]Fluoro 2,3 dioxo 1,2,3,4 tetrahydroquinoxaline
6 carbonitrile (c.a. [18F]FCQX) 71
4.7.7 Determination of the molar activity 72
4.8 Pharmacological evaluation 73
4.8.1 In vitro autoradiography 73
4.8.2 Ex vivo autoradiography 74
5 Summary 75
6 References 78 |
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| spelling | Olma, Sebastian Verfasser aut Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling von Sebastian Olma Jülich Graph. Betriebe der Forschungszentrum Jülich GmbH 2007 89 S. Ill. txt rdacontent n rdamedia nc rdacarrier Auch als: Berichte des Forschungszentrums Jülich ; 4252 Zugl.: Köln, Univ., Diss., 2007 Rezeptor (DE-588)4049722-7 gnd rswk-swf Zolazepam (DE-588)4601314-3 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Rezeptor (DE-588)4049722-7 s Zolazepam (DE-588)4601314-3 s 1\p DE-604 Köln (DE-588)2015732-0 gnd uvp http://digitool.hbz-nrw.de:1801/webclient/DeliveryManager?pid=1999800&custom_att_2=simple_viewer Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor Inhaltsverzeichnis HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016214767&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Olma, Sebastian Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling Rezeptor (DE-588)4049722-7 gnd Zolazepam (DE-588)4601314-3 gnd |
| subject_GND | (DE-588)4049722-7 (DE-588)4601314-3 (DE-588)4113937-9 |
| title | Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling |
| title_auth | Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling |
| title_exact_search | Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling |
| title_exact_search_txtP | Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling |
| title_full | Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling von Sebastian Olma |
| title_fullStr | Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling von Sebastian Olma |
| title_full_unstemmed | Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor development of synthetic strategies and labeling von Sebastian Olma |
| title_short | Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor |
| title_sort | radiofluorinated quinoxalinedione derivatives as putative ligands of the ampa receptor development of synthetic strategies and labeling |
| title_sub | development of synthetic strategies and labeling |
| topic | Rezeptor (DE-588)4049722-7 gnd Zolazepam (DE-588)4601314-3 gnd |
| topic_facet | Rezeptor Zolazepam Hochschulschrift |
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