Design and synthesis of tetrahydropyridopyrimidine based Toll-Like Receptor (TLR) 7/8 dual agonists

被引：10

作者：

McGowan, David C. ^{[1
]}

Herschke, Florence ^{[1
]}

Khamlichi, Mourad D. ^{[2
]}

Luz Rosauro, Mari ^{[2
]}

Perez Benedicto, Sara M. ^{[2
]}

Pauwels, Frederik ^{[1
]}

Stoops, Bart ^{[1
]}

Pande, Vineet ^{[1
]}

Scholliers, Annick ^{[1
]}

Van Schoubroeck, Bertrand ^{[1
]}

Mostmans, Wendy ^{[1
]}

Van Dijck, Kris ^{[1
]}

Thone, Tine ^{[1
]}

Horton, Helen ^{[1
]}

Fanning, Gregory ^{[1
]}

Jonckers, Tim H. M. ^{[1
]}

Raboisson, Pierre ^{[1
]}

机构：

[1] Janssen Infect Dis, Turnhoutseweg 30, B-2340 Beerse, Belgium

[2] Villapharma Res, Parque Tecnol Fuente Alamo, Murcia 30320, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 19期

关键词：

Immunomodulator; Toll-Like Receptor; TLR7/8; Tetrahydropyridopyrimidine; SINGLE-STRANDED RNA; CHRONIC HEPATITIS-B; LINKING INNATE; RECOGNITION; INHIBITORS; POTENT; IDENTIFICATION; DERIVATIVES; DISCOVERY; EFFICACY;

D O I：

10.1016/j.bmcl.2018.08.015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In a continuing effort to discover novel TLR agonists, herein we report on the discovery and structure-activity relationship of novel tetrahydropyridopyrimidine TLR 7/8 agonists. Optimization of this series towards dual agonist activity and a high clearance profile resulted in the identification of compound 52a1. Evaluation in vivo revealed an interferon stimulated response (ISG) in mice with limited systemic exposure and demonstrated the potential in antiviral treatment or as a vaccine adjuvant.

引用

页码：3216 / 3221

页数：6

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