1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid | 1195737-19-9

• 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: 1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid
• CAS: 1195737-19-9
• 化学式: C₁₃H₁₆N₄O₂
• 分子量: 260.296
• InChiKey: PSJYOGLYEIDIRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  82.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid 、 甲氧苯胺 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(4-methoxyphenyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
  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
• 作为产物：
  描述：

  在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid
  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

• 4-Piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine compounds
  申请人：Rawlins Brent David

  公开号：US20060189638A1

  公开（公告）日：2006-08-24

  Substituted 4-piperidin-1-yl-7H-pyrrolo[2,3-D]pyrimidine compounds are disclosed, as well as compositions comprising them and methods of their use for the treatment, prevention and management of various diseases and disorders.

  本发明揭示了替代的4-哌啶-1-基-7H-吡咯并[2,3-D]嘧啶化合物，以及包含它们的组合物和它们的使用方法，用于治疗、预防和管理各种疾病和障碍。
• 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.
• US7423043B2
  申请人：——

  公开号：US7423043B2

  公开（公告）日：2008-09-09
• [EN] 4-PIPERIDIN-1-YL-7H-PYRROLO[2,3-D]PYRIMIDINE COMPOUNDS<br/>[FR] COMPOSES 4-PIPERIDIN-1-YL-7H-PYRROLO[2,3-D]PYRIMIDINE
  申请人：LEXICON GENETICS INC

  公开号：WO2006091450A1

  公开（公告）日：2006-08-31

  [EN] Substituted 4-piperidin-l -yl-7H-pyrrolo[2,3-D]pyrirnidine compounds are disclosed, as well as compositions comprising them and methods of their use for the treatment, prevention and management of various diseases and disorders.
  [FR] Cette invention concerne des composés 4-pipéridin-1-yl-7H-pyrrolo[2,3-d]pyrimidine substitués ainsi que des compositions contenant ces composés et des procédés d'utilisation de ces composés pour le traitement, la prévention et la gestion de diverses maladies et divers troubles.
• 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.