4-methyl-2,3-dihydro-1H-indole hydrochloride | 1187928-38-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-methyl-2,3-dihydro-1H-indole hydrochloride
• 英文别名: 4-methyl-indoline; hydrochloride；4-Methyl-indolin; Hydrochlorid；4-Methylindoline hydrochloride；4-methyl-2,3-dihydro-1H-indole;hydrochloride
• CAS: 1187928-38-6
• 化学式: C₉H₁₁N*ClH
• 分子量: 169.654
• InChiKey: IEIFWNWARZLMPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.38
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  12
• 氢给体数：
  2
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  ethyl [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate 、 4-methyl-2,3-dihydro-1H-indole hydrochloride 在 sodium hydroxide 、 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 以6%的产率得到2-[2-(4-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one
  参考文献：
  名称：

  Discovery and Optimization of Pyrimidone Indoline Amide PI3Kβ Inhibitors for the Treatment of Phosphatase and Tensin Homologue (PTEN)-Deficient Cancers

  摘要：

  Compelling molecular biology publications have reported the implication of phosphoinositide kinase PI3K beta in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for the development of PI3K beta-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (7) and the optimization of this new series of active and selective pyrimidone indoline amide PI3K beta inhibitors. 2-[2-(2-Methyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (28), identified following a carefully designed methyl scan, displayed improved physicochemical and in vitro pharmacokinetic properties. Structural biology efforts enabled the acquisition of the first X-ray cocrystal structure of p110 beta with the selective inhibitor compound 28 bound to the ATP site. The nonplanar binding mode described herein is consistent with observed structure-activity relationship for the series. Compound 28 demonstrated significant in vivo activity in a UACC-62 xenograft model in mice, warranting further preclinical investigation. Following successful development, compound 28 entered phase I/Ib clinical trial in patients with advanced cancer.

  DOI：

  10.1021/jm401642q

文献信息

• NOVEL COMPOUNDS
  申请人：Gottschling Dirk

  公开号：US20110195954A1

  公开（公告）日：2011-08-11

  The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R 1 , R 2 , R 3 and R 4 are defined as mentioned in the description, the tautomers thereof, the isomers thereof, the diastereomers thereof, the enantiomers thereof, the hydrates thereof, the mixtures thereof and the salts thereof as well as the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, the use thereof and processes for the preparation thereof.

  本发明涉及一般式I的新CGRP拮抗剂，其中U、V、X、Y、R1、R2、R3和R4如描述中所述定义，其互变异构体、异构体、顺反异构体、对映异构体、水合物、混合物及其盐，以及其盐的水合物，特别是与无机或有机酸或碱形成的生理上可接受的盐，包含这些化合物的药物、其用途以及其制备方法。
• NOVEL (6-OXO-1,6-DIHYDROPYRIMIDIN-2-YL)AMIDE DERIVATIVES, PREPARATION THEREOF AND PHARMACEUTICAL USE THEREOF AS AKT(PKB) PHOSPHORYLATION INHIBITORS
  申请人：CARRY Jean-Christophe

  公开号：US20120270867A1

  公开（公告）日：2012-10-25

  The invention relates to the novel materials of formula (I), where: R1 is an optionally substituted aryl or heteroaryl; R is an H or, when formed with R1, a 5- or 6-member ring fused with an aryl or heretoaryl group optionally containing one or more of O, S, N, NH, and Nalk, being optionally substituted; R2 and R3 are, independently, an H, Hal, or alkyl optionally substituted by one or more Hal; R4 is H; and R5 is an H or alkyl optionally substituted by one or more halogen atoms. Said materials being in any isomeric form and the salts thereof, and are intended for drugs, particularly AKT(PKB) phosphorylation inhibitors.

  本发明涉及公式（I）的新型材料，其中：R1是可选择取代的芳基或杂环芳基；R是H或与R1形成的5-或6-成员环，与可选择含有O、S、N、NH和Nalk中的一种或多种的芳基或杂环芳基团融合，可选择取代；R2和R3分别为H、卤素或可选择取代的1个或多个卤素的烷基；R4为H；R5为H或可选择取代的1个或多个卤素原子的烷基。所述材料以任何异构形式及其盐的形式存在，用于药物，特别是AKT（PKB）磷酸化抑制剂。
• (6-oxo-1,6-dihydropyrimidin-2-yl)amide derivatives, preparation thereof and pharmaceutical use thereof as AKT(PKB) phosphorylation inhibitors
  申请人：Carry Jean-Christophe

  公开号：US08791255B2

  公开（公告）日：2014-07-29

  The invention relates to the novel materials of formula (I), wherein each of the substituents R, R1, R2, R3, R4 and R5 is as defined herein. The materials are useful as inhibitors of AKT(PKB) phosphorylation.

  本发明涉及式(I)的新型材料，其中取代基R、R1、R2、R3、R4和R5的定义如本文所述。该材料可用作AKT（PKB）磷酸化抑制剂。
• Designed switch from covalent to non-covalent inhibitors of carboxylesterase Notum activity
  作者：Benjamin N. Atkinson、Nicky J. Willis、Yuguang Zhao、Chandni Patel、Sarah Frew、Kathryn Costelloe、Lorenza Magno、Fredrik Svensson、E. Yvonne Jones、Paul V. Fish

  DOI：10.1016/j.ejmech.2023.115132

  日期：2023.5

  palmiteolate pocket with key interactions being aromatic stacking and a water mediated hydrogen bond to the oxyanion hole. These N-acyl indolines 4 will be useful tools for use in vitro studies to investigate the role of Notum in disease models, especially when paired with a structurally related covalent inhibitor (e.g. 4w and 2a). Overall, this study highlights the designed switch from covalent to non-covalent

  N-酰基二氢吲哚4是有效的非共价 Notum 抑制剂，由共价虚拟筛选命中2a开发而成。先导化合物合成简单，在生化 Notum-OPTS 测定中实现了优异的效力，并在基于细胞的 TCF/LEF 报告基因测定中恢复了 Wnt 信号传导。多个高分辨率X射线结构建立了这些抑制剂的共同结合模式，二氢吲哚结合在棕榈醇酸袋的中心，关键相互作用是芳族堆积和水介导的与氧阴离子孔的氢键。这些N -酰基二氢吲哚4将成为体外研究的有用工具，用于研究 Notum 在疾病模型中的作用，特别是与结构相关的共价抑制剂（例如4w和2a）配对时。总的来说，这项研究强调了从共价到非共价 Notum 抑制剂的设计转换，因此说明了命中生成和目标抑制的补充方法。
• US8791255B2
  申请人：——

  公开号：US8791255B2

  公开（公告）日：2014-07-29