1-[2-氯-4-(甲基磺酰基)苯基]哌嗪 | 849035-72-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-[2-氯-4-(甲基磺酰基)苯基]哌嗪
• 英文名称: 1-(4-chloro-2-(methylsulfonyl)phenyl)piperazine
• 英文别名: 1-[4-Chloro-2-(methylsulfonyl)phenyl]piperazine；1-(4-chloro-2-methylsulfonylphenyl)piperazine
• CAS: 849035-72-9
• 化学式: C₁₁H₁₅ClN₂O₂S
• 分子量: 274.771
• InChiKey: RJEDJYJNERXVNE-UHFFFAOYSA-N

物化性质

• 熔点：
  139-141°C

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  57.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  1-[2-氯-4-(甲基磺酰基)苯基]哌嗪 在 甲酸 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.42h， 生成 1-methyl-4-(2-(methylsulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine
  参考文献：
  名称：

  The Discovery of Orally Bioavailable Tyrosine Threonine Kinase (TTK) Inhibitors: 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides as Anticancer Agents

  摘要：

  The acetamido and carboxamido substituted 3-(1H-indazol-3-yl)benzenesulfonamides are potent TTK inhibitors. However, they display modest ability to attenuate cancer cell growth; their physicochemical properties, and attendant pharmacokinetic parameters, are not drug-like. By eliminating the polar 3-sulfonamide group and grafting a heterocycle at the 4 position of the phenyl ring, potent inhibitors with oral exposure were obtained. An X-ray cocrystal structure and a refined binding model allowed for a structure guided approach. Systematic optimization resulted in novel TTK inhibitors, namely 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides. Compounds incorporating the 3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl bicyclic system were potent (TTK IC50 < 10 nM, HCT116 GI(50) < 0.1 mu M), displayed low off-target activity (>500X), and microsomal stability (T-1/2 > 30 min). A subset was tested in rodent PK and mouse xenograft models of human cancer. Compound 75 (CFI-401870) recapitulated the phenotype of TTK RNAi, demonstrated in vivo tumor growth inhibition upon oral dosing, and was selected for preclinical evaluation.

  DOI：

  10.1021/jm501740a

文献信息

• [EN] KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME<br/>[FR] INHIBITEURS DE KINASES ET PROCÉDÉ DE TRAITEMENT DU CANCER UTILISANT CEUX-CI
  申请人：UNIV HEALTH NETWORK

  公开号：WO2011123937A1

  公开（公告）日：2011-10-13

  The present teachings provide a compound represented by Strutural Formula (I): or a pharmaceutically acceptable salt thereof. Also described are a pharmaceutical composition and method of use thereof.

  本教学提供了一种由结构式(I)表示的化合物，或其药用可接受的盐。还描述了一种药物组合物及其使用方法。
• Aromatic Compound
  申请人：Furukubo Shigeru

  公开号：US20090182142A1

  公开（公告）日：2009-07-16

  An aromatic compound represented by the following formula or a pharmaceutically acceptable salt thereof: , wherein ring A is a heterocyclic ring, ring B is a carbocyclic ring, a heterocyclic ring etc., G 1 , G 2 , G 3 , G 4 and G 5 are CH or N, X is —NH—, —O—, —CH 2 —, etc., Y is —CH 2 —, —CO—, —SO 2 —, etc., Z is a single bond, —CO—, —SO 2 —, —NH—, —O—, —S—, —CONH—, —SO 2 NH—, etc., R 2 is hydrogen, alkyl, alkoxy, halogen, etc., and R 3 is carbocyclic group, heterocyclic group, alkyl, etc., is useful as a controlling agent of the function of CCR4 useful for the treatment or therapy for bronchial asthma, atopic dermatitis, etc.

  下列的芳香族化合物或其药学上可接受的盐，其化学式如下：其中环A为杂环，环B为碳环、杂环等，G1、G2、G3、G4和G5为CH或N，X为—NH—、—O—、—CH2—等，Y为—CH2—、—CO—、—SO2—等，Z为单键、—CO—、—SO2—、—NH—、—O—、—S—、—CONH—、—SO2NH—等，R2为氢、烷基、烷氧基、卤素等，而R3为碳环基、杂环基、烷基等。该化合物对于控制CCR4功能的作用剂对于治疗或治疗支气管哮喘、特应性皮炎等疾病是有用的。
• The Discovery of Orally Bioavailable Tyrosine Threonine Kinase (TTK) Inhibitors: 3-(4-(heterocyclyl)phenyl)-1<i>H</i>-indazole-5-carboxamides as Anticancer Agents
  作者：Yong Liu、Yunhui Lang、Narendra Kumar Patel、Grace Ng、Radoslaw Laufer、Sze-Wan Li、Louise Edwards、Bryan Forrest、Peter B. Sampson、Miklos Feher、Fuqiang Ban、Donald E. Awrey、Irina Beletskaya、Guodong Mao、Richard Hodgson、Olga Plotnikova、Wei Qiu、Nickolay Y. Chirgadze、Jacqueline M. Mason、Xin Wei、Dan Chi-Chia Lin、Yi Che、Reza Kiarash、Brian Madeira、Graham C. Fletcher、Tak W. Mak、Mark R. Bray、Henry W. Pauls

  DOI：10.1021/jm501740a

  日期：2015.4.23

  The acetamido and carboxamido substituted 3-(1H-indazol-3-yl)benzenesulfonamides are potent TTK inhibitors. However, they display modest ability to attenuate cancer cell growth; their physicochemical properties, and attendant pharmacokinetic parameters, are not drug-like. By eliminating the polar 3-sulfonamide group and grafting a heterocycle at the 4 position of the phenyl ring, potent inhibitors with oral exposure were obtained. An X-ray cocrystal structure and a refined binding model allowed for a structure guided approach. Systematic optimization resulted in novel TTK inhibitors, namely 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides. Compounds incorporating the 3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl bicyclic system were potent (TTK IC50 < 10 nM, HCT116 GI(50) < 0.1 mu M), displayed low off-target activity (>500X), and microsomal stability (T-1/2 > 30 min). A subset was tested in rodent PK and mouse xenograft models of human cancer. Compound 75 (CFI-401870) recapitulated the phenotype of TTK RNAi, demonstrated in vivo tumor growth inhibition upon oral dosing, and was selected for preclinical evaluation.