[1-(6-{6-[(1-methylethyl)amino]-1H-indazol-1-yl}pyrazin-2-yl)-1H-pyrrol-3-yl]acetic acid | 940882-70-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: [1-(6-{6-[(1-methylethyl)amino]-1H-indazol-1-yl}pyrazin-2-yl)-1H-pyrrol-3-yl]acetic acid
• 英文别名: 2-[1-[6-[6-(propan-2-ylamino)indazol-1-yl]pyrazin-2-yl]pyrrol-3-yl]acetic acid
• CAS: 940882-70-2
• 化学式: C₂₀H₂₀N₆O₂
• 分子量: 376.418
• InChiKey: BBYRUZKRFAIQSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  97.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 2-[1-(6-iodopyrazin-2-yl)-1H-pyrrol-3-yl]acetate 在 potassium phosphate 、 copper(l) iodide 、 (1S,2S)-(+)-1,2-环己二胺 、 水 、 sodium cyanoborohydride 、 溶剂黄146 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 [1-(6-{6-[(1-methylethyl)amino]-1H-indazol-1-yl}pyrazin-2-yl)-1H-pyrrol-3-yl]acetic acid
  参考文献：
  名称：

  Discovery and structure–activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2

  摘要：

  We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.006

文献信息

• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• [EN] METHODS AND SYSTEMS OF STRATIFYING INFLAMMATORY DISEASE PATIENTS<br/>[FR] PROCÉDÉS ET SYSTÈMES POUR STRATIFICATION DE PATIENTS ATTEINTS DE MALADIE INFLAMMATOIRE
  申请人：[en]CEDARS-SINAI MEDICAL CENTER

  公开号：WO2022119842A1

  公开（公告）日：2022-06-09

  Described herein are methods and systems for identifying subpopulations of inflammatory bowel disease (IBD) patients utilizing genetic markers that are associated with severe Crohn's disease. Further provided are therapies useful for treating these subpopulations of IBD patients based, at least in part, on the genetic markers provided herein.
• Discovery and structure–activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2
  作者：Nobuhiro Fuchi、Yosuke Iura、Hiroaki Kaneko、Aiko Nitta、Kazuharu Suyama、Hiroshi Ueda、Shinichi Yamaguchi、Kazumi Nishimura、Shigeo Fujii、Yumiko Sekiya、Masateru Yamada、Toshiya Takahashi

  DOI：10.1016/j.bmcl.2012.05.006

  日期：2012.7

  We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis. (C) 2012 Elsevier Ltd. All rights reserved.