Synthesis and evaluation of 2-pyridinylpyrimidines as inhibitors of HIV-1 structural protein assembly
In an effort to identify an HIV-1 capsid assembly inhibitor with improved solubility and potency, we synthesized two series of pyrimidine analogues based on our earlier lead compound N-(4-(ethoxycarbonyl)phenyl)-2-(pyridine-4-yl)quinazoline-4-amine. In vitro binding experiments showed that our serie...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
1 August 2016
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| In: |
Bioorganic & medicinal chemistry letters
Year: 2016, Volume: 26, Issue: 15, Pages: 3487-3490 |
| ISSN: | 1464-3405 |
| DOI: | 10.1016/j.bmcl.2016.06.039 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.bmcl.2016.06.039 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0960894X16306503 
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| Author Notes: | Milan Kožíšek, Ondřej Štěpánek, Kamil Parkan, Carlos Berenguer Albiñana, Marcela Pávová, Jan Weber, Hans-Georg Krӓusslich, Jan Konvalinka, Aleš Machara |
| Summary: | In an effort to identify an HIV-1 capsid assembly inhibitor with improved solubility and potency, we synthesized two series of pyrimidine analogues based on our earlier lead compound N-(4-(ethoxycarbonyl)phenyl)-2-(pyridine-4-yl)quinazoline-4-amine. In vitro binding experiments showed that our series of 2-pyridine-4-ylpyrimidines had IC50 values higher than 28μM. Our series of 2-pyridine-3-ylpyrimidines exhibited IC50 values ranging from 3 to 60μM. The congeners with a fluoro substituent introduced at the 4-N-phenyl moiety, along with a methyl at C-6, represent potent HIV capsid assembly inhibitors binding to the C-terminal domain of the capsid protein. |
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| Item Description: | Gesehen am 28.11.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1464-3405 |
| DOI: | 10.1016/j.bmcl.2016.06.039 |