1-(methoxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid | 502498-89-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 1-(methoxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid
• 英文别名: 1-Methoxyimino-indan-5-boronic acid；(1-methoxyimino-2,3-dihydroinden-5-yl)boronic acid
• CAS: 502498-89-7
• 化学式: C₁₀H₁₂BNO₃
• 分子量: 205.021
• InChiKey: UVWBADYWXYEXEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.34
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,3-二溴呋喃 、 1-(methoxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid 生成 5-(3-Bromofuran-2-yl)indan-1-one o-methyloxime
  参考文献：
  名称：

  Pyridylfurans and pyrroles as raf kinase inhibitors

  摘要：

  化合物及其作为制药品的用途，特别是作为Raf激酶抑制剂用于治疗神经创伤性疾病、癌症、慢性神经退行性疾病、疼痛、偏头痛和心脏肥大。

  公开号：

  US20040254186A1
• 作为产物：
  描述：

  (Z)-5-溴-2,3-二氢-1H-茚-1-酮 O-甲基 肟 在 正丁基锂 、 硼酸三甲酯 作用下， 以 四氢呋喃 为溶剂， 以58%的产率得到1-(methoxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid
  参考文献：
  名称：

  The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase

  摘要：

  Modification of the potent imidazole-based B-Raf inhibitor SB-590885 resulted in the identification of a series of furan-based derivatives with enhanced CNS penetration. One such compound, SB-699393 (17), was examined in vivo to challenge the hypothesis that selective B-Raf inhibitors may be of value in the treatment of stroke. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.06.070

文献信息

• Pyridylfurans and pyrroles as Raf kinase inhibitors
  申请人：SmithKline Beechum P.L.C.

  公开号：US07297694B2

  公开（公告）日：2007-11-20

  Compounds and their use as pharmaceuticals particularly as Raf kinase inhibitors for the treatment of neurotraumatic diseases, cancer, chronic neurodegeneration, pain, migraine and cardiac hypertrophy.

  化合物及其作为药物的使用，特别是作为Raf激酶抑制剂，用于治疗神经创伤性疾病、癌症、慢性神经退行性疾病、疼痛、偏头痛和心肌肥厚。
• Pyridine derivatives as Raf kinase inhibitors
  申请人：SmithKline Beecham P.L.C.

  公开号：US07452906B2

  公开（公告）日：2008-11-18

  Compounds and their use as pharmaceuticals particularly as Raf kinase inhibitors for the treatment of neurotraumatic diseases, cancer, chronic neurodegeneration, pain, migraine and cardiac hypertrophy.

  化合物及其用途作为药物，特别是作为Raf激酶抑制剂治疗神经创伤性疾病、癌症、慢性神经退行性疾病、疼痛、偏头痛和心肌肥厚。
• Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds
  作者：Dan Niculescu-Duvaz、Ion Niculescu-Duvaz、Bart M.J.M. Suijkerbuijk、Delphine Ménard、Alfonso Zambon、Arnaud Nourry、Lawrence Davies、Helen A. Manne、Frank Friedlos、Lesley Ogilvie、Douglas Hedley、Andrew K. Takle、David M. Wilson、Jean-Francois Pons、Tom Coulter、Ruth Kirk、Neus Cantarino、Steven Whittaker、Richard Marais、Caroline J. Springer

  DOI：10.1016/j.bmc.2010.06.031

  日期：2010.9

  V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin- 4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a) was identified as an active BRAF inhibitor. Based on this starting point, we synthesized a series of analogues leading to the discovery of 6-2-[4-(4-methylpiperazin- 1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno[1,2-c]pyrazole (1j), with nanomolar activity in three assays: inhibition of purified mutant BRAF activity in vitro; inhibition of oncogenic BRAF-driven extracellular regulated kinase (ERK) activation in BRAF mutant melanoma cell lines; and inhibition of proliferation in these cells. (C) 2010 Elsevier Ltd. All rights reserved.