Synthesis, crystal structures and anti-inflammatory activity of fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine derivatives
Two fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine (BQA) derivatives, namely 2-amino-4-(2-fluorophenyl)-9-methoxy-1,4,5,6-tetrahydrobenzo[h]quinazolin-3-ium chloride, (8), and 2-amino-4-(4-fluorophenyl)-9-methoxy-1,4,5,6-tetrahydrobenzo[h]quinazolin-3-ium chloride, (9), both C19H19FN3O+·Cl-, were generated by Michael addition reactions between guanidine hydrochloride and the α,β-unsaturated ketones (E)-2-(2-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C18H15FO2, (6), and (E)-2-(4-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, (7). Because both sides of α,β-unsaturated ketones (6) or (7) can be attacked by guanidine, we obtained a pair of isomers in (8) and (9). Single-crystal X-ray diffraction indicates that each isomer has a chiral C atom and both (8) and (9) crystallize in the achiral space group P21/c. The chloride ion, as a hydrogen-bond acceptor, plays an important role in the formation of multiple hydrogen bonds. Thus, adjacent molecules are connected through intermolecular hydrogen bonds to generate a banded structure. Furthermore, these bands are linked into an interesting 3D network via hydrogen bonds and π-π interactions. Fortunately, the solubilities of (8) and (9) were distinctly improved and can exceed 50 mg ml-1 in water or PBS buffer system (pH 7.4) at room temperature. In addition, the results of an investigation of anti-inflammatory activity show that (8) and (9), with o- and p-fluoro substituents, respectively, display more potential for inhibitory effects on LPS-induced NO secretion than starting ketones (6) and (7).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:75 |
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| Enthalten in: |
Acta crystallographica. Section C, Structural chemistry - 75(2019), Pt 8 vom: 01. Aug., Seite 1157-1165 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Yue [VerfasserIn] |
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| Links: |
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| Themen: |
1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine |
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| Anmerkungen: |
Date Revised 09.08.2019 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1107/S2053229619010118 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM299920585 |
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| 245 | 1 | 0 | |a Synthesis, crystal structures and anti-inflammatory activity of fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine derivatives |
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| 500 | |a Date Revised 09.08.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Two fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine (BQA) derivatives, namely 2-amino-4-(2-fluorophenyl)-9-methoxy-1,4,5,6-tetrahydrobenzo[h]quinazolin-3-ium chloride, (8), and 2-amino-4-(4-fluorophenyl)-9-methoxy-1,4,5,6-tetrahydrobenzo[h]quinazolin-3-ium chloride, (9), both C19H19FN3O+·Cl-, were generated by Michael addition reactions between guanidine hydrochloride and the α,β-unsaturated ketones (E)-2-(2-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C18H15FO2, (6), and (E)-2-(4-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, (7). Because both sides of α,β-unsaturated ketones (6) or (7) can be attacked by guanidine, we obtained a pair of isomers in (8) and (9). Single-crystal X-ray diffraction indicates that each isomer has a chiral C atom and both (8) and (9) crystallize in the achiral space group P21/c. The chloride ion, as a hydrogen-bond acceptor, plays an important role in the formation of multiple hydrogen bonds. Thus, adjacent molecules are connected through intermolecular hydrogen bonds to generate a banded structure. Furthermore, these bands are linked into an interesting 3D network via hydrogen bonds and π-π interactions. Fortunately, the solubilities of (8) and (9) were distinctly improved and can exceed 50 mg ml-1 in water or PBS buffer system (pH 7.4) at room temperature. In addition, the results of an investigation of anti-inflammatory activity show that (8) and (9), with o- and p-fluoro substituents, respectively, display more potential for inhibitory effects on LPS-induced NO secretion than starting ketones (6) and (7) | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine | |
| 650 | 4 | |a anti-inflammatory activity | |
| 650 | 4 | |a crystal structure | |
| 650 | 4 | |a water solubility | |
| 700 | 1 | |a Gao, Zhongfei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chunhua |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Guige |e verfasserin |4 aut | |
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