Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: Design, synthesis, and biological activities

被引：48

作者：

Di Santo, Roberto ^{[1
]}

Costi, Roberta ^{[1
]}

Roux, Alessandra ^{[1
]}

Miele, Gaetano ^{[1
]}

Crucitti, Giuliana Cuzzucoli ^{[1
]}

Iacovo, Alberto ^{[1
]}

Rosi, Federica ^{[1
]}

Lavecchia, Antonio ^{[2
]}

Marinelli, Luciana ^{[2
]}

Di Giovanni, Carmen ^{[2
]}

Novellino, Ettore ^{[2
]}

Palmisano, Lucia ^{[3
]}

Andreotti, Mauro ^{[3
]}

Amici, Roberta ^{[3
]}

Galluzzo, Clementina Maria ^{[3
]}

Nencioni, Lucia ^{[4
]}

Palamara, Anna Teresa ^{[4
]}

Pommier, Yves ^{[5
]}

Marchand, Christophe ^{[5
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, I-00185 Rome, Italy

[2] Univ Naples Federico 2, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy

[3] Ist Super Sanita, Dipartimento Farmaco, I-00161 Rome, Italy

[4] Univ Roma La Sapienza, Dipartimento Sci Sanita Pubbl, I-00185 Rome, Italy

[5] NCI, NIH, Ctr Canc Res, Mol Phys Lab, Bethesda, MD 20892 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 15期

关键词：

D O I：

10.1021/jm8001422

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.

引用

页码：4744 / 4750

页数：7

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