SR7280 | 1296199-29-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: SR7280
• 英文别名: N-(3-methoxybenzyl)-3-(morpholinomethyl)-6-(1H-pyrazol-4-yl)-1H-indole-2-carboxamide；N-[(3-methoxyphenyl)methyl]-3-(morpholin-4-ylmethyl)-6-(1H-pyrazol-4-yl)-1H-indole-2-carboxamide
• CAS: 1296199-29-5
• 化学式: C₂₅H₂₇N₅O₃
• 分子量: 445.521
• InChiKey: USACHTMSCZBEJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  95.3
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-Bromo-N-(3-methoxybenzyl)-1H-indole-2-carboxamide 在 trans-bis(triphenylphosphine)palladium dichloride 、 sodium carbonate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 SR7280
  参考文献：
  名称：

  Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (Part-II)

  摘要：

  Therapeutic interventions with Rho kinase (ROCK) inhibitors may effectively treat several disorders such as hypertension, stroke, cancer, and glaucoma. Herein we disclose the optimization and biological evaluation of potent novel ROCK inhibitors based on substituted indole and 7-azaindole core scaffolds. Substitutions on the indole C3 position and on the indole NH and/or amide NH positions all yielded potent and selective ROCK inhibitors (25, 42, and 50). Improvement of aqueous solubility and tailoring of in vitro and in vivo DMPK properties could be achieved through these substitutions. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.084

文献信息

• [EN] BICYCLIC HETEROARYLS AS KINASE INHIBITORS<br/>[FR] HÉTÉROARYLES BICYCLIQUES FORMANT INHIBITEURS DE LA KINASE
  申请人：FENG YANGBO

  公开号：WO2011050245A1

  公开（公告）日：2011-04-28

  The invention is directed to heteroaryl compounds useful as inhibitors of various kinase enzymes. In various embodiments, the invention provides a heteroaryl compound having inhibitory bioactivity with respect to a Rho kinase, an AKT kinase, a p70S6K kinase, a LIM kinase, an IKK kinase, a Flt kinase, an Aurora kinase, or a Src kinase, or any combination thereof. Compounds of the invention include bicyclic heteroaryl compounds of formula (I), which can contain a bridging nitrogen atom at a ring junction. The invention further provides methods of synthesis of compounds of the invention, pharmaceutical compositions, pharmaceutical combinations, and methods of treatment of malconditions using compounds of the invention.

  该发明涉及对各种激酶酶的抑制剂作为杂环芳基化合物的用途。在各种实施形式中，该发明提供了一种具有抑制生物活性的杂环芳基化合物，该生物活性与Rho激酶、AKT激酶、p70S6K激酶、LIM激酶、IKK激酶、Flt激酶、Aurora激酶或Src激酶或其任意组合相关。该发明的化合物包括具有式(I)的双环杂环芳基化合物，该化合物在环的连接处可以含有一个桥接氮原子。该发明还提供了合成该发明化合物的方法、药物组合物、药物组合以及使用该发明化合物治疗病症的方法。
• Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (Part-II)
  作者：E. Hampton Sessions、Sarwat Chowdhury、Yan Yin、Jennifer R. Pocas、Wayne Grant、Thomas Schröter、Li Lin、Claudia Ruiz、Michael D. Cameron、Philip LoGrasso、Thomas D. Bannister、Yangbo Feng

  DOI：10.1016/j.bmcl.2011.09.084

  日期：2011.12

  Therapeutic interventions with Rho kinase (ROCK) inhibitors may effectively treat several disorders such as hypertension, stroke, cancer, and glaucoma. Herein we disclose the optimization and biological evaluation of potent novel ROCK inhibitors based on substituted indole and 7-azaindole core scaffolds. Substitutions on the indole C3 position and on the indole NH and/or amide NH positions all yielded potent and selective ROCK inhibitors (25, 42, and 50). Improvement of aqueous solubility and tailoring of in vitro and in vivo DMPK properties could be achieved through these substitutions. (C) 2011 Elsevier Ltd. All rights reserved.