6-aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays

被引：40

作者：

Costi, R

Di Santo, R

Artico, M

Roux, A

Ragno, R

Massa, S

Tramontano, E

La Colla, M

Loddo, R

Marongiu, ME

Pani, A

La Colla, P

机构：

[1] Univ Roma La Sapienza, Dipartimento Studi Farmaceut, Fdn Cenci Bolognetti, Inst Pasteur, I-00185 Rome, Italy

[2] Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy

[3] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Sostanze Biologicament, I-00185 Rome, Italy

[4] Univ Cagliari, Sez Microbiol, Dipartimento Biol Sperimentale, I-09042 Cagliari, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 07期

关键词：

diketoacids; aryldioxohexenoic acids; pyrrole derivatives; anti-HIV-1-IN agents; QSAR studies;

D O I：

10.1016/j.bmcl.2004.01.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 6-aryl-2,4-dioxo-5-hexenoic acids, were synthesized and tested against HIV-1 in cell-based assays and against recombinant HIV-1 integrase (rIN) in enzyme assays. Compound 8a showed potent antiretroviral activity (EC50 = 1.5 muM) and significant inhibition against rIN (strand transfer: IC50 = 7.9 muM; 3'-processing: IC50 = 7.0 muM). A preliminary molecular modeling study was carried out to compare the spatial conformation of 8a with those of L-731,988 (4) and 5CITEP (7) in the IN core. (C) 2004 Elsevier Ltd. All rights reserved.

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收藏

页码：1745 / 1749

页数：5

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