(E)-3-[3-(3,4,5,6-Tetrahydro-2H-[1,2']bipyrazinyl-6'-yl)phenyl]acrylic acid | 1006699-36-0

• 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: (E)-3-[3-(3,4,5,6-Tetrahydro-2H-[1,2']bipyrazinyl-6'-yl)phenyl]acrylic acid
• 英文别名: (E)-3-[3-(3,4,5,6-tetrahydro-2H-[1,2]bipyrazinyl-6'-yl)-phenyl]-acrylic acid；(2E)-3-{3-[6-(piperazin-1-yl)pyrazin-2-yl]phenyl}prop-2-enoic acid；(E)-3-[3-(6-piperazin-1-ylpyrazin-2-yl)phenyl]prop-2-enoic acid
• CAS: 1006699-36-0
• 化学式: C₁₇H₁₈N₄O₂
• 分子量: 310.356
• InChiKey: FODQNTDRJCXQQJ-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  78.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (E)-3-(3-BORONOPHENYL)ACRYLICACID锛圵S203778锛,WUXIAPPTEC" 、 MK 212盐酸盐 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (E)-3-[3-(3,4,5,6-Tetrahydro-2H-[1,2']bipyrazinyl-6'-yl)phenyl]acrylic acid
  参考文献：
  名称：

  Hit to Lead Account of the Discovery of a New Class of Inhibitors of Pim Kinases and Crystallographic Studies Revealing an Unusual Kinase Binding Mode

  摘要：

  A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed.

  DOI：

  10.1021/jm801242y

文献信息

• PYRAZINE COMPOUNDS, THEIR USE AND METHODS OF PREPARATION
  申请人：Mao Wang

  公开号：US20100210627A1

  公开（公告）日：2010-08-19

  The invention provides compounds according to formula (I) their use and methods for preparation wherein A, X, Y, R1, R2 and R3 are defined herein. The compounds of the invention inhibit specific serine/threonine kinases involved in inflammatory processes and aberrant cell proliferation, and are thus useful for treating associated diseases and pathological conditions such as Pim kinase-mediated diseases and pathological conditions involving inflammation, including Chron's disease, inflammatory bowel disease, rheumatoid arthritis, and chronic inflammatory disease, or aberrant cell proliferation including various cancers.

  该发明提供了根据式(I)的化合物及其用途和制备方法，其中A、X、Y、R1、R2和R3在此处被定义。该发明的化合物抑制参与炎症过程和异常细胞增殖的特定丝氨酸/苏氨酸激酶，因此可用于治疗相关疾病和病理条件，如Pim激酶介导的疾病和涉及炎症的病理条件，包括克罗恩病、炎性肠病、类风湿关节炎和慢性炎症性疾病，或异常细胞增殖，包括各种癌症。
• US8318723B2
  申请人：——

  公开号：US8318723B2

  公开（公告）日：2012-11-27
• [EN] PYRAZINE COMPOUNDS, THEIR USE AND METHODS OF PREPARATION<br/>[FR] COMPOSÉS DE PYRAZINE, LEUR UTILISATION ET PROCÉDÉS DE PRÉPARATION
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2008022164A2

  公开（公告）日：2008-02-21

  [EN] The invention provides compounds according to formula (I) their use and methods for preparation wherein A, X, Y, R1, R2 and R3 are defined herein. The compounds of the invention inhibit specific serine/threonine kinases involved in inflammatory processes and aberrant cell proliferation, and are thus useful for treating associated diseases and pathological conditions such as Pim kinase-mediated diseases and pathological conditions involving inflammation, including Chron's disease, inflammatory bowel disease, rheumatoid arthritis, and chronic inflammatory disease, or aberrant cell proliferation including various cancers.
  [FR] L'invention concerne des composés représentés par la formule (I), leur utilisation et des procédés de préparation, A, X, Y, R1, R2 et R3 étant tels que définis ici. Les composés de l'invention inhibent des kinases de sérine/thréonine spécifiques impliquées dans des processus inflammatoires et des proliférations cellulaires aberrantes, et sont donc utiles pour traiter des maladies et des conditions pathologiques associées, telles que les maladies favorisées par Pim kinase, ainsi que des conditions pathologiques impliquant une inflammation, dont la maladie de Crohn, la maladie intestinale inflammatoire, l'arthrite rhumatoïde et la maladie inflammatoire chronique, ou une prolifération cellulaire aberrante, dont divers cancers.
• Hit to Lead Account of the Discovery of a New Class of Inhibitors of Pim Kinases and Crystallographic Studies Revealing an Unusual Kinase Binding Mode
  作者：Kevin Qian、Lian Wang、Charles L. Cywin、Bennett T. Farmer、Eugene Hickey、Carol Homon、Scott Jakes、Mohammed A. Kashem、George Lee、Scott Leonard、Jun Li、Ronald Magboo、Wang Mao、Edward Pack、Charlene Peng、Anthony Prokopowicz、Morgan Welzel、John Wolak、Tina Morwick

  DOI：10.1021/jm801242y

  日期：2009.4.9

  A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed.