(S)-5-methyl-4-(3-methylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine | 1116570-96-7

• 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)-5-methyl-4-(3-methylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 5-methyl-4-[(3S)-3-methylpiperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine
• CAS: 1116570-96-7
• 化学式: C₁₂H₁₇N₅
• 分子量: 231.3
• InChiKey: BUCDLBVNVQNEAO-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  56.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-5-methyl-4-(3-methylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine 、 N-氰基羰亚胺二苯基酯 以 乙腈 为溶剂， 以86%的产率得到(S)-phenyl N-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carbimidate
  参考文献：
  名称：

  KINASE INHIBITORS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE

  摘要：

  抑制LIM激酶2的抑制剂已被披露，以及包含它们的药物组合物和使用方法。

  公开号：

  US20090042893A1
• 作为产物：
  描述：

  (S)-tert-butyl 2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxylate 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 以76%的产率得到(S)-5-methyl-4-(3-methylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  KINASE INHIBITORS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE

  摘要：

  抑制LIM激酶2的抑制剂已被披露，以及包含它们的药物组合物和使用方法。

  公开号：

  US20090042893A1

文献信息

• Substituted pyrrolo[2,3-d]pyrimidines as LIM kinase 2 inhibitors
  申请人：Harrison Bryce Alden

  公开号：US08507672B2

  公开（公告）日：2013-08-13

  Substituted pyrrolo[2,3-d]pyrimidine-based compounds useful as inhibitors of LIM kinase 2 are disclosed. Also disclosed are pharmaceutical compositions comprising the compounds and methods of their use to treat, manage and prevent inflammatory diseases and disorders, cancer, and diseases and disorders of the eye.

  本发明揭示了一种基于替代吡咯并[2,3-d]嘧啶的化合物，可作为LIM激酶2的抑制剂。还揭示了包含这些化合物的药物组合物以及它们的使用方法，用于治疗、管理和预防炎症性疾病和障碍、癌症以及眼部疾病和障碍。
• (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。
• Discovery and Development of LX7101, a Dual LIM-Kinase and ROCK Inhibitor for the Treatment of Glaucoma
  作者：Bryce A. Harrison、Zheng Y. Almstead、Hugh Burgoon、Michael Gardyan、Nicole C. Goodwin、Jason Healy、Ying Liu、Ross Mabon、Brett Marinelli、Lakshman Samala、Yulian Zhang、Terry R. Stouch、N. Andrew Whitlock、Suma Gopinathan、Beth McKnight、Shuli Wang、Nita Patel、Alan G. E. Wilson、Brian D. Hamman、Dennis S. Rice、David B. Rawlins

  DOI：10.1021/ml500367g

  日期：2015.1.8

  The structure of LX7101, a dual LIM-kinase and ROCK inhibitor for the treatment of ocular hypertension and associated glaucoma, is disclosed. Previously reported LIM kinase inhibitors suffered from poor aqueous stability due to solvolysis of the central urea. Replacement of the urea with a hindered amide resulted in aqueous stable compounds, and addition of solubilizing groups resulted in a set of compounds with good properties for topical dosing in the eye and good efficacy in a mouse model of ocular hypertension. LX7101 was selected as a clinical candidate from this group based on superior efficacy in lowering intraocular pressure and a good safety profile. LX7101 completed IND enabling studies and was tested in a Phase 1 clinical trial in glaucoma patients, where it showed efficacy in lowering intraocular pressure.
• 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.
• (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