Identification of novel PI3K inhibitors through a scaffold hopping strategy

被引：8

作者：

Martinez Gonzalez, Sonia ^{[1
]}

Isabel Hernandez, Ana ^{[1
]}

Maria Alvarez, Rosa ^{[1
]}

Rodriguez, Antonio ^{[1
,2
]}

Ramos-Lima, Francisco ^{[1
]}

Bischoff, James R. ^{[1
,3
]}

Isabel Albarran, Maria ^{[1
]}

Cebria, Antonio ^{[1
]}

Hernandez-Encinas, Elena ^{[1
]}

Garcia-Arocha, Jennifer ^{[1
]}

Cebrian, David ^{[1
,4
]}

Blanco-Aparicio, Carmen ^{[1
]}

Pastor, Joaquin ^{[1
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, Expt Therapeut Programme, C Melchor Fernandez Almagro 3, E-28029 Madrid, Spain

[2] Ctr Invest Lilly SA, Avda Ind,30, E-28108 Madrid, Spain

[3] F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Grenzacherstr 124, CH-4070 Basel, Switzerland

[4] GSK, Pharmacol Unit, Dis Developing World, C Severo Ochoa,2,Sci Business Technol Pk, E-28760 Madrid, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 21期

关键词：

Scaffold hopping; ETP-46321; PI3K inhibitors; Back-up; CANCER; OPPORTUNITIES; CHALLENGES; ETP-46321; 3-KINASES; POTENT;

D O I：

10.1016/j.bmcl.2017.09.059

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A scaffold hopping strategy, including intellectual property availability assessment, was successfully applied for the discovery of novel PI3K inhibitors. Compounds were designed based on the chemical structure of the lead compound ETP-46321, a potent PI3K inhibitor, previously reported by our group. The new generated compounds showed good in vitro potency and selectivity, proved to inhibit potently the phosphorylation of AKT(Ser473) in cells and demonstrated to be orally bioavailable, thus becoming potential back-up candidates for ETP-46321. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：4794 / 4799

页数：6

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