Synthesis and evaluation of C2-carbon-linked heterocyclic-5-hydroxy-6-oxo-dihydropyrimidine-4-carboxamides as HIV-1 integrase inhibitors

被引：38

作者：

Naidu, B. Narasimhulu ^{[1
]}

Sorenson, Margaret E. ^{[1
]}

Patel, Manoj ^{[1
]}

Ueda, Yasutsugu ^{[1
]}

Banville, Jacques ^{[1
]}

Beaulieu, Francis ^{[1
]}

Bollini, Sagarika ^{[2
]}

Dicker, Ira B. ^{[2
]}

Higley, Helen ^{[2
]}

Lin, Zeyu ^{[2
]}

Pajor, Lori ^{[3
]}

Parker, Dawn D. ^{[3
]}

Terry, Brian J. ^{[2
]}

Zheng, Ming ^{[3
]}

Martel, Alain ^{[1
]}

Meanwell, Nicholas A. ^{[1
]}

Krystal, Mark ^{[2
]}

Walker, Michael A. ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Dept Discovery Chem, Res & Dev, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Co, Dept Virol, Res & Dev, Wallingford, CT 06492 USA

[3] Bristol Myers Squibb Co, Pharmaceut Candidate Optimizat, Res & Dev, Wallingford, CT 06492 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 03期

关键词：

HIV-1; Integrase; Strand transfer; Inhibitor; Pyrimidine-4-carboxamide; ONE-POT SYNTHESIS; RALTEGRAVIR;

D O I：

10.1016/j.bmcl.2014.11.060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Integration of viral DNA into the host cell genome is an obligatory process for successful replication of HIV-1. Integrase catalyzes the insertion of viral DNA into the target DNA and is a validated target for drug discovery. Herein, we report the synthesis, antiviral activity and pharmacokinetic profiles of several C2-carbon-linked heterocyclic pyrimidinone-4-carboxamides that inhibit the strand transfer step of the integration process. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：717 / 720

页数：4

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