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- Publisher Website: 10.1021/jm990600c
- Scopus: eid_2-s2.0-0034077984
- PMID: 10821715
- WOS: WOS:000087223900013
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Article: A new class of HIV-1 integrase inhibitors: The 3,3,3',3'-tetramethyl- 1,1'-spirobi(indan)-5,5',6,6'-tetrol family
Title | A new class of HIV-1 integrase inhibitors: The 3,3,3',3'-tetramethyl- 1,1'-spirobi(indan)-5,5',6,6'-tetrol family |
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Authors | |
Issue Date | 2000 |
Citation | Journal of Medicinal Chemistry, 2000, v. 43, n. 10, p. 2031-2039 How to Cite? |
Abstract | Integration is a required step in HIV replication, but as yet no inhibitors of the integration step have been developed for clinical use. Many inhibitors have been identified that are active against purified viral- encoded integrase protein; of these, many contain a catechol moiety. Though this substructure contributes potency in inhibitors, it is associated with toxicity and so the utility of catechol-containing inhibitors has been questioned. We have synthesized and tested a systematic series of derivatives of a catechol-containing inhibitor (1) with the goal of identifying catechol isosteres that support inhibition. We find that different patterns of substitution on the aromatic ring suffice for inhibition when Mn2+ is used as a cofactor. Importantly, the efficiency is different when Mg2+, the more likely in vivo cofactor, is used. These data emphasize the importance of assays with Mg2+ and offer new catechol isosteres for use in integrase inhibitors. |
Persistent Identifier | http://hdl.handle.net/10722/341502 |
ISSN | 2023 Impact Factor: 6.8 2023 SCImago Journal Rankings: 1.986 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Molteni, Valentina | - |
dc.contributor.author | Rhodes, Denise | - |
dc.contributor.author | Rubins, Kathleen | - |
dc.contributor.author | Hansen, Mark | - |
dc.contributor.author | Bushman, Frederic D. | - |
dc.contributor.author | Siegel, Jay S. | - |
dc.date.accessioned | 2024-03-13T08:43:18Z | - |
dc.date.available | 2024-03-13T08:43:18Z | - |
dc.date.issued | 2000 | - |
dc.identifier.citation | Journal of Medicinal Chemistry, 2000, v. 43, n. 10, p. 2031-2039 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | http://hdl.handle.net/10722/341502 | - |
dc.description.abstract | Integration is a required step in HIV replication, but as yet no inhibitors of the integration step have been developed for clinical use. Many inhibitors have been identified that are active against purified viral- encoded integrase protein; of these, many contain a catechol moiety. Though this substructure contributes potency in inhibitors, it is associated with toxicity and so the utility of catechol-containing inhibitors has been questioned. We have synthesized and tested a systematic series of derivatives of a catechol-containing inhibitor (1) with the goal of identifying catechol isosteres that support inhibition. We find that different patterns of substitution on the aromatic ring suffice for inhibition when Mn2+ is used as a cofactor. Importantly, the efficiency is different when Mg2+, the more likely in vivo cofactor, is used. These data emphasize the importance of assays with Mg2+ and offer new catechol isosteres for use in integrase inhibitors. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Medicinal Chemistry | - |
dc.title | A new class of HIV-1 integrase inhibitors: The 3,3,3',3'-tetramethyl- 1,1'-spirobi(indan)-5,5',6,6'-tetrol family | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1021/jm990600c | - |
dc.identifier.pmid | 10821715 | - |
dc.identifier.scopus | eid_2-s2.0-0034077984 | - |
dc.identifier.volume | 43 | - |
dc.identifier.issue | 10 | - |
dc.identifier.spage | 2031 | - |
dc.identifier.epage | 2039 | - |
dc.identifier.isi | WOS:000087223900013 | - |