Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1

BravoY.; TerieteP.; DhanyaR.-P.; DahlR.; LeeP.S.; Kiffer-MoreiraT.; GanjiS.R.; SergienkoE.; SmithL.H.; FarquharsonC.; MillánJ.L.; CosfordN.D.P.

首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1

【24h】

Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1

机译：苯并异噻唑酮作为PHOSPHO1选择性抑制剂的设计，合成和评估

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

We report the discovery and characterization of a series of benzoisothiazolone inhibitors of PHOSPHO1, a newly identified soluble phosphatase implicated in skeletal mineralization and soft tissue ossification abnormalities. High-throughput screening (HTS) of a small molecule library led to the identification of benzoisothiazolones as potent and selective inhibitors of PHOSPHO1. Critical structural requirements for activity were determined, and the compounds were subsequently derivatized and measured for in vitro activity and ADME parameters including metabolic stability and permeability. On the basis of its overall profile the benzoisothiazolone analogue 2q was selected as MLPCN probe ML086.

机译：我们报告发现和表征一系列的苯并异噻唑酮抑制剂PHOSPHO1，一种新发现的可溶性磷酸酶，与骨骼矿化和软组织骨化异常有关。小分子文库的高通量筛选（HTS）导致鉴定苯并异噻唑酮为PHOSPHO1的有效抑制剂和选择性抑制剂。确定了活性的关键结构要求，随后将化合物衍生化并测量了体外活性和ADME参数，包括代谢稳定性和通透性。根据其总体概况，选择苯并异噻唑酮类似物2q作为MLPCN探针ML086。

著录项

来源
《Bioorganic and Medicinal Chemistry Letters》 |2014年第17期|共4页
作者
BravoY.; TerieteP.; DhanyaR.-P.; DahlR.; LeeP.S.; Kiffer-MoreiraT.; GanjiS.R.; SergienkoE.; SmithL.H.; FarquharsonC.; MillánJ.L.; CosfordN.D.P.;
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
ML086; Phosphatase; PHOSPHO1; Probe compound; Vascular calcification;

机译：ML086;磷酸酶;PHOSPHO1;探针化合物;血管钙化;

相似文献

外文文献
中文文献
专利

1. Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1 [J] . BravoY., TerieteP., DhanyaR.-P., Bioorganic and Medicinal Chemistry Letters . 2014,第17期

机译：苯并异噻唑酮作为PHOSPHO1选择性抑制剂的设计，合成和评估
2. The design, synthesis, and biological evaluation of analogues of the serine-threonine protein phosphatase 1 and 2A selective inhibitor microcystin LA: rational modifications imparting PP1 selectivity. [J] . Aggen JB, Humphrey JM, Gauss CM, Bioorganic and medicinal chemistry . 1999,第3期

机译：丝氨酸-苏氨酸蛋白磷酸酶1和2A选择性抑制剂微囊藻毒素LA的类似物的设计，合成和生物学评估：合理的修饰赋予PP1选择性。
3. Design, synthesis and evaluation of marinopyrrole derivatives as selective inhibitors of Mcl-1 binding to pro-apoptotic Bim and dual Mcl-1/Bc1-xL inhibitors [J] . Li Rongshi, Cheng Chunwei, Balasis Maria E., European Journal of Medicinal Chemistry: Chimie Therapeutique . 2015,第Null期

机译：设计，合成和评估马来吡咯衍生物作为Mcl-1选择性抑制剂与促凋亡Bim和双重Mcl-1 / Bc1-xL抑制剂的结合
4. Design, Synthesis, and Pharmacological Evaluation of Novel Tasiamide B Derivatives: Selective Inhibitors of BACE1 [C] . Jian Liu, SimingYang, Wei Zhang, Chinese International Peptide Symposium . 2013

机译：新型三胺B衍生物的设计，合成和药理评价：BACE1的选择性抑制剂
5. The design, synthesis, and biophysical evaluation of small molecules to study and selectively inhibit transthyretin amyloidosis. [D] . Johnson, Steven M. 2006

机译：小分子的设计，合成和生物物理评估，以研究和选择性抑制运甲状腺素蛋白淀粉样变性。
6. Design Synthesis and Evaluation of Benzoisothiazolones as Selective Inhibitors of PHOSPHO1 [O] . Yalda Bravo, Peter Teriete, Raveendra-Panickar Dhanya, -1

机译：设计合成和评价苯甲异噻唑酮类作为PHOSPHO1的选择性抑制剂
7. Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1 [O] . Yalda Bravo, Peter Teriete, Raveendra-Panickar Dhanya, 2014

机译：苯甲苯胺的设计，合成与评价，作为磷酸的选择性抑制剂
8. Design, Synthesis, and Evaluation of Estrogen Sulfotransferase Inhibitors: Potential Enhancers of Tamoxifen-Mediated Apoptosis in ER Negative Breast Cancers [R] . Peterson, B. R. 2002

机译：雌激素磺基转移酶抑制剂的设计，合成和评价：他莫昔芬介导的ER阴性乳腺癌细胞凋亡的潜在增强剂

Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1

摘要

著录项

相似文献

相关主题

期刊订阅