Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent gamma;-Secretase Modulators

Bischoff F.; Berthelot D.; De Cleyn M.; MacDonald G.; Minne G.; Oehlrich D.; Pieters S.; Surkyn M.; Trabanco A.A.; Tresadern G.; Van Brandt S.; Velter I.; Zaja M.; Borghys H.; Masungi C.; Mercken M.; Gijsen H.J.M.

首页> 外文期刊>Journal of Medicinal Chemistry >Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent gamma;-Secretase Modulators

【24h】

Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent gamma;-Secretase Modulators

机译：设计和合成的新型双环杂环作为有效的γ;分泌酶调节剂

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

The design and the synthesis of several chemical subclasses of imidazole containing gamma;-secretase modulators (GSMs) is described. Conformational restriction of pyridone 4 into bicyclic pyridone isosteres has led to compounds with high in vitro and in vivo potency. This has resulted in the identification of benzimidazole 44a as a GSM with low nanomolar potency in vitro. In mouse, rat, and dog, this compound displayed the typical gamma;-secretase modulatory profile by lowering Aβ42 and Aβ40 levels combined with an especially pronounced increase in Aβ38 and Aβ37 levels while leaving the total levels of amyloid peptides unchanged.

机译：描述了咪唑的几种化学亚类的设计和合成，这些化学亚类包含γ-分泌酶调节剂（GSM）。吡啶酮4在双环吡啶酮等构物中的构象限制已导致化合物具有高的体外和体内效力。这导致将苯并咪唑44a鉴定为体外纳摩尔浓度低的GSM。在小鼠，大鼠和狗中，该化合物通过降低Aβ42和Aβ40水平以及特别明显的Aβ38和Aβ37水平升高，同时保持淀粉样肽总水平不变，显示出典型的γ-分泌酶调节特性。

著录项

来源
《Journal of Medicinal Chemistry》 |2012年第21期|共18页
作者
Bischoff F.; Berthelot D.; De Cleyn M.; MacDonald G.; Minne G.; Oehlrich D.; Pieters S.; Surkyn M.; Trabanco A.A.; Tresadern G.; Van Brandt S.; Velter I.; Zaja M.; Borghys H.; Masungi C.; Mercken M.; Gijsen H.J.M.;
展开▼
作者单位

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类
关键词

相似文献

外文文献
中文文献
专利

1. Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent gamma;-Secretase Modulators [J] . Bischoff F., Berthelot D., De Cleyn M., Journal of Medicinal Chemistry . 2012,第21期

机译：设计和合成的新型双环杂环作为有效的γ;分泌酶调节剂
2. Design and synthesis of bicyclic heterocycles as potent γ-secretase modulators [J] . OehlrichD., RomboutsF.J.R., BerthelotD., Bioorganic and Medicinal Chemistry Letters . 2013,第17期

机译：双环杂环作为有效的γ-分泌酶调节剂的设计与合成
3. Design and synthesis of a novel series of cyanoindole derivatives as potent gamma-secretase modulators [J] . Bischoff Francois P., Velter Adriana Ingrid, Minne Garrett, Bioorganic and Medicinal Chemistry Letters . 2019,第14期

机译：一种新型氰基吲哚衍生物系列的设计与合成有效的γ-分泌酶调节剂
4. DESIGN,SYNTHESIS AND CHARACTERIZATION OF NOVEL SERIES OF 1,3-THIAZOLE CONTAINING HETEROCYCLES AS INHIBITORS OF DHFR FOR USE AS ANTICANCER AGENTS [C] . Sunil Dilip Pawar, Mithila N.S., Abhishek Yadav Conference on Drug Design and Discovery Technologies . 2020

机译：用作DHFR抑制剂用作抗癌剂的DHFR抑制剂的设计，合成及表征
5. Synthesis of new glutamate receptor probes: I. Total synthesis of dysiherbaine, a potent glutamate receptor excitotoxin; II. Design and synthesis of dysiherbaine analogues; III. Synthesis and structure-activity relationships of substituted benzothiadiazides and their role as AMPA receptor modulators. [D] . Phillips, Dean Paul. 2001

机译：新型谷氨酸受体探针的合成：I. dysiherbaine的全合成，一种有效的谷氨酸受体兴奋性毒素；二。 dysiherbaine类似物的设计和合成；三，取代的苯并噻二叠氮化物的合成及其构效关系及其作为AMPA受体调节剂的作用。
6. Discovery of a Potent Pyrazolopyridine Series of γ-Secretase Modulators [O] . Jun Qin, *, Wei Zhou, 2011

机译：高效的吡唑并吡啶系列γ-秘密酶调节剂的发现
7. An approach to design potent anti-Alzheimer’s agents by 3D-QSAR studies on fused 5,6-bicyclic heterocycles as γ-secretase modulators using kNN–MFA methodology [O] . Kamlendra Singh Bhadoriya, Mukesh C. Sharma, Smita Sharma, 2014

机译：使用kNN-mFa方法通过3D-QsaR研究将融合的5,6-双环杂环作为γ-分泌酶调节剂设计有效的抗阿尔茨海默病药物的方法

Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent gamma;-Secretase Modulators

摘要

著录项

相似文献

相关主题

期刊订阅