tert-butyl 3-(3-aminophenoxy)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 3-(3-aminophenoxy)piperidine-1-carboxylate
• 英文别名: Tert-butyl 3-(3-aminophenoxy)piperidine-1-carboxylate
• 化学式: C₁₆H₂₄N₂O₃
• 分子量: 292.378
• InChiKey: UWRYMAUCFQPCQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(3-aminophenoxy)piperidine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-(3-(piperidin-3-yloxy)phenyl)-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Discovery of N-(3-((1-Isonicotinoylpiperidin-4-yl)oxy)-4-methylphenyl)-3-(trifluoromethyl)benzamide (CHMFL-KIT-110) as a Selective, Potent, and Orally Available Type II c-KIT Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  c-KIT kinase is a validated drug discovery target for gastrointestinal stromal tumors (GISTs). Clinically used c-KIT kinase inhibitors, i.e., Imatinib and Sunitinib, bear other important targets such as ABL or FLT3 kinases. Here we report our discovery of a more selective c-KIT inhibitor, compound 13 (CHMFL-KIT-110), which completely abolished ABL and FLT3 kinase activity. KinomeScan selectivity profiling (468 kinases) of 13 exhibited a high selectivity (S score (1) = 0.01). 13 displayed great antiproliferative efficacy against GISTs cell lines GIST-T1 and GIST-882 (GI50: 0.021 and 0.043 mu M, respectively). In the cellular context, it effectively affected c-KIT-mediated signaling pathways and induced apoptosis as well as cell cycle arrest. In addition, 13 possessed acceptable bioavailability (36%) and effectively suppressed the tumor growth in GIST-T1 cell inoculated xenograft model without apparent toxicity. 13 currently is undergoing extensive preclinical evaluation and might be a potential drug candidate for GISTs.

  DOI：

  10.1021/acs.jmedchem.6b00200
• 作为产物：
  描述：

  N-BOC-3-羟基哌啶 在 偶氮二甲酸二异丙酯 、 5%-palladium/activated carbon 、 氢气 、 三苯基膦 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 tert-butyl 3-(3-aminophenoxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of N-(3-((1-Isonicotinoylpiperidin-4-yl)oxy)-4-methylphenyl)-3-(trifluoromethyl)benzamide (CHMFL-KIT-110) as a Selective, Potent, and Orally Available Type II c-KIT Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  c-KIT kinase is a validated drug discovery target for gastrointestinal stromal tumors (GISTs). Clinically used c-KIT kinase inhibitors, i.e., Imatinib and Sunitinib, bear other important targets such as ABL or FLT3 kinases. Here we report our discovery of a more selective c-KIT inhibitor, compound 13 (CHMFL-KIT-110), which completely abolished ABL and FLT3 kinase activity. KinomeScan selectivity profiling (468 kinases) of 13 exhibited a high selectivity (S score (1) = 0.01). 13 displayed great antiproliferative efficacy against GISTs cell lines GIST-T1 and GIST-882 (GI50: 0.021 and 0.043 mu M, respectively). In the cellular context, it effectively affected c-KIT-mediated signaling pathways and induced apoptosis as well as cell cycle arrest. In addition, 13 possessed acceptable bioavailability (36%) and effectively suppressed the tumor growth in GIST-T1 cell inoculated xenograft model without apparent toxicity. 13 currently is undergoing extensive preclinical evaluation and might be a potential drug candidate for GISTs.

  DOI：

  10.1021/acs.jmedchem.6b00200

文献信息

• Discovery of PqsE Thioesterase Inhibitors for <i>Pseudomonas aeruginosa</i> Using DNA-Encoded Small Molecule Library Screening
  作者：Julie S. Valastyan、Michael R. Tota、Isabelle R. Taylor、Vasiliki Stergioula、Graham A. B. Hone、Chari D. Smith、Brad R. Henke、Kenneth G. Carson、Bonnie L. Bassler

  DOI：10.1021/acschembio.9b00905

  日期：2020.2.21

  making PqsE an attractive target for inhibition. Neither the substrate nor the product of PqsE catalysis has been identified. A library of 550 million DNA-encoded drug-like small molecules was screened for those that bind to the purified PqsE protein. The structures of the bound molecules were identified by high throughput sequencing of the attached DNA barcodes. Putative PqsE binders with the strongest

  铜绿假单胞菌是美国医院获得性感染的主要原因。PqsE 是一种硫酯酶，对铜绿假单胞菌的毒力至关重要，这使得 PqsE 成为一个有吸引力的抑制目标。PqsE 催化的底物和产物均未鉴定。筛选了一个包含 5.5 亿个 DNA 编码的药物样小分子的文库，以寻找那些与纯化的 PqsE 蛋白结合的小分子。通过连接的 DNA 条形码的高通量测序鉴定结合分子的结构。在体外检测了具有最强亲和力特征的假定 PqsE 结合剂对 PqsE 硫酯酶活性的抑制作用. 最有效的抑制剂从 DNA 中重新合成，并检查了改变 PqsE 热熔解和 PqsE 硫酯酶抑制的能力。在这里，我们报告了一系列非竞争性抑制 PqsE 的 2-(苯基氨基甲酰基)苯甲酸的合成、生物活性、作用机制和早期构效关系。设计用于探测初始结构-活性关系的一小组类似物显示出相对于原始命中物的效力增加，其中最好的具有 IC 50 = 5 μM。由于目前的化合物