Synthesis and dopamine receptor pharmacological evaluations on ring C ortho halogenated 1-phenylbenzazepines
Copyright © 2020 Elsevier Ltd. All rights reserved..
A series of 1-phenylbenzazepines containing bromine or chlorine substituents at the ortho position of the appended phenyl ring (2'-monosubstituted or 2',6'- disubstituted patterns) were synthesized and evaluated for affinity towards dopamine D1R, D2R and D5R. As is typical of the 1-phenylbenzazepine scaffold, the compounds displayed selectivity towards D1R and D5R; analogs generally lacked affinity for D2R. Interestingly, 2',6'-dichloro substituted analogs showed modest D5R versus D1R selectivity whereas this selectivity was reversed in compounds with a 2'-halo substitution pattern. Compound 10a was identified as a D1R antagonist (Ki = 14 nM; IC50 = 9.4 nM).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Bioorganic & medicinal chemistry letters - 30(2020), 16 vom: 15. Aug., Seite 127305 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Giri, Rajan [VerfasserIn] |
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| Links: |
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| Themen: |
Benzazepine |
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| Anmerkungen: |
Date Completed 01.06.2021 Date Revised 16.08.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmcl.2020.127305 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31209194X |
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| 520 | |a Copyright © 2020 Elsevier Ltd. All rights reserved. | ||
| 520 | |a A series of 1-phenylbenzazepines containing bromine or chlorine substituents at the ortho position of the appended phenyl ring (2'-monosubstituted or 2',6'- disubstituted patterns) were synthesized and evaluated for affinity towards dopamine D1R, D2R and D5R. As is typical of the 1-phenylbenzazepine scaffold, the compounds displayed selectivity towards D1R and D5R; analogs generally lacked affinity for D2R. Interestingly, 2',6'-dichloro substituted analogs showed modest D5R versus D1R selectivity whereas this selectivity was reversed in compounds with a 2'-halo substitution pattern. Compound 10a was identified as a D1R antagonist (Ki = 14 nM; IC50 = 9.4 nM) | ||
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| 650 | 4 | |a Dopamine | |
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| 700 | 1 | |a Alberts, Ian |e verfasserin |4 aut | |
| 700 | 1 | |a Harding, Wayne W |e verfasserin |4 aut | |
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