(S)-N'-cyano-N-(3-cyanophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(trifluoromethyl)phenyl)piperazine-1-carboximidamide | 1116570-38-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (S)-N'-cyano-N-(3-cyanophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(trifluoromethyl)phenyl)piperazine-1-carboximidamide
• 英文别名: (S)-N'-cyano-N-(3-cyanophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide；(2S)-N-cyano-N'-(3-cyanophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide
• CAS: 1116570-38-7
• 化学式: C₂₁H₂₁N₉
• 分子量: 399.458
• InChiKey: SDZJESDWVOOOKS-HNNXBMFYSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-5-methyl-4-(3-methylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine 、 phenyl N-cyano-N'-(3-cyanophenyl)carbamimidate 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成 (S)-N'-cyano-N-(3-cyanophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(trifluoromethyl)phenyl)piperazine-1-carboximidamide
  参考文献：
  名称：

  Novel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma

  摘要：

  The discover), of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may bean effective target for treating ocular hypertension and associated glaucoma.

  DOI：

  10.1021/jm901226j

文献信息

• (7H-PYRROLO [2, 3-D] PYRIMIDIN-4-YL) -PIPERAZINES AS KINASE INHIBITORS FOR THE TREATMENT OF CANCER AND INFLAMMATION
  申请人：Lexicon Pharmaceuticals, Inc.

  公开号：EP2597098A1

  公开（公告）日：2013-05-29

  Inhibitors of LIM kinase 2 of the following formula are disclosed, along with pharmaceutical compositions comprising them and methods of their use, in particular for treatment of inflammatory and cancerous and ocular diseases. X is O or NRA; A is cycloalkyl, aryl or heterocyclyl; RA is hydrogen, cyano, nitro, RA1, SO2RA1 or SO2N(RA1)2; each RB is independently hydrogen or alkyl. The other variables are as defined in the claims.

  本研究公开了下式的 LIM 激酶 2 抑制剂，以及包含这些抑制剂的药物组合物和使用方法，尤其是用于治疗炎症、癌症和眼部疾病的方法。 X 是 O 或 NRA； A 是环烷基、芳基或杂环基； RA 是氢、氰基、硝基、RA1、SO2RA1 或 SO2N(RA1)2 每个 RB 独立地为氢或烷基。 其他变量如权利要求中所定义。
• (7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-PIPERAZINES AS KINASE INHIBITORS FOR THE TREATMENT OF CANCER AND INFLAMMATION
  申请人：Lexicon Pharmaceuticals, Inc.

  公开号：EP2188289B1

  公开（公告）日：2015-10-28
• [EN] KINASE INHIBITORS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE<br/>[FR] INHIBITEURS DE KINASE, COMPOSITIONS LES CONTENANT ET PROCÉDÉS D'UTILISATION
  申请人：LEXICON PHARMACEUTICALS INC

  公开号：WO2009021169A2

  公开（公告）日：2009-02-12

  Inhibitors of LIM kinase 2 are disclosed, along with pharmaceutical compositions com πsin them and methods of their use. X is O or NRA; Y is O, NRR, or C(RR)2; A is cycloalkyl, aryl or hctcrocyclc; RA is hydrogen, cyano, nitro, RA1, SO2RA1, SO2NRA1, or SO2N(RA1)2;
• Novel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma
  作者：Bryce A. Harrison、N. Andrew Whitlock、Michael V. Voronkov、Zheng Y. Almstead、Kun-jian Gu、Ross Mabon、Michael Gardyan、Brian D. Hamman、Jason Allen、Suma Gopinathan、Beth McKnight、Mike Crist、Yulian Zhang、Ying Liu、Lawrence F. Courtney、Billie Key、Julia Zhou、Nita Patel、Phil W. Yates、Qingyun Liu、Alan G. E. Wilson、S. David Kimball、Craig E. Crosson、Dennis S. Rice、David B. Rawlins

  DOI：10.1021/jm901226j

  日期：2009.11.12

  The discover), of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may bean effective target for treating ocular hypertension and associated glaucoma.