Synthesis of a novel tricyclic 1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline ring system and CXCR4 antagonists with potent activity against HIV-1

被引：33

作者：

Catalano, John G. ^{[1
]}

Gudmundsson, Kristjan S. ^{[1
]}

Svolto, Angilique ^{[1
]}

Boggs, Sharon D. ^{[1
]}

Miller, John F. ^{[1
]}

Spaltenstein, Andrew ^{[1
]}

Thomson, Michael ^{[2
]}

Wheelan, Pat ^{[3
]}

Minick, Doug J. ^{[4
]}

Phelps, Dean P. ^{[4
]}

Jenkinson, Stephen ^{[5
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Dept Med Chem, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

[2] GlaxoSmithKline Res & Dev Ltd, Dept Virol, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

[3] GlaxoSmithKline Res & Dev Ltd, Dept DMPK, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

[4] GlaxoSmithKline Res & Dev Ltd, Dept Analyt Chem, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

[5] GlaxoSmithKline Res & Dev Ltd, Dept Biochem & Analyt Pharmacol, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 07期

关键词：

CXCR4; HIV; AIDS; Inhibitor; Antiviral; Viral; Entry; Chemokine; VIBRATIONAL CIRCULAR-DICHROISM; IMMUNODEFICIENCY-VIRUS TYPE-1; ABSOLUTE-CONFIGURATION; CHIRAL MOLECULES; INHIBITION; ENTRY;

D O I：

10.1016/j.bmcl.2010.02.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Stereorandom and diastereoselective syntheses of a novel 1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline ring system are described. Derivatives of all four diastereomers were prepared and isolated in >98% ee. The pure enantiomers were compared in order to determine the preferred absolute and relative configuration required for optimal anti-HIV activity. Anti-HIV potency and pharmacokinetic properties of the newly synthesized tricyclic octahydrophenanthroline inhibitors are presented and comparisons are made to previously reported bicyclic (8S)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine analogs. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2186 / 2190

页数：5

共 21 条

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