Identification of Fast-Acting 2,6-Disubstituted Imidazopyridines That Are Efficacious in the in Vivo Humanized Plasmodium falciparum NODscidIL2Rγnull Mouse Model of Malaria,Journal of Medicinal Chemistry

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Identification of Fast-Acting 2,6-Disubstituted Imidazopyridines That Are Efficacious in the in Vivo Humanized Plasmodium falciparum NODscidIL2Rγnull Mouse Model of Malaria
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2018-04-17 00:00:00 , DOI: 10.1021/acs.jmedchem.8b00382
Aloysius T. Nchinda ₁ , Claire Le Manach ₁ , Tanya Paquet ₁ , Diego Gonzàlez Cabrera ₁ , Kathryn J. Wicht ₁ , Christel Brunschwig ₂ , Mathew Njoroge ₂ , Efrem Abay ₂ , Dale Taylor ₂ , Nina Lawrence ₂ , Sergio Wittlin _{3,

4} , María-Belén Jiménez-Díaz ₅ , María Santos Martínez ₅ , Santiago Ferrer ₅ , Iñigo Angulo-Barturen ₅ , Maria Jose Lafuente-Monasterio ₅ , James Duffy ₆ , Jeremy Burrows ₆ , Leslie J. Street ₁ , Kelly Chibale _{1,

7}

Affiliation

Optimization of a chemical series originating from whole-cell phenotypic screening against the human malaria parasite, Plasmodium falciparum, led to the identification of two promising 2,6-disubstituted imidazopyridine compounds, 43 and 74. These compounds exhibited potent activity against asexual blood stage parasites that, together with their in vitro absorption, distribution, metabolism, and excretion (ADME) properties, translated to in vivo efficacy with clearance of parasites in the PfSCID mouse model for malaria within 48 h of treatment.

中文翻译：

速效2,6-二取代咪唑并吡啶类鉴定这是有效的在体内人性化的恶性疟原虫NODscidIL2Rγ^空疟疾的小鼠模型

从全细胞表型筛选针对人类疟疾寄生虫，恶性疟原虫的化学系列的优化导致鉴定了两个有前途的2，6-二取代的咪唑并吡啶化合物43和74。这些化合物显示出对无性血液阶段寄生虫的有效活性，以及它们的体外吸收，分布，代谢和排泄（ADME）特性，在Pf SCID小鼠模型中可在48小时内清除疟原虫的体内寄生虫，转化为体内功效的治疗。

更新日期：2018-04-17

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