4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt
• 英文别名: 4-cyano-1-(2-trimethylsilanylethoxymethyl)-1H-imidazole-2-carboxylate potassium salt；potassium 4-cyano-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate；potassium 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate；potassium 4-cyano-1-(2-trimethylsilanylethoxymethyl)-1H-imidazole-2-carboxylate；4-cyano-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate potassium salt；potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate；potassium;4-cyano-1-(2-trimethylsilylethoxymethyl)imidazole-2-carboxylate
• 化学式: C₁₁H₁₆N₃O₃Si*K
• 分子量: 305.45
• InChiKey: BNQGKHUEVQWESM-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.57
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  91
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt 以92%的产率得到4-cyano-N-(2-(4,4-dimethylcyclohex-1-en-1-yl)-6-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxamide
  参考文献：
  名称：

  INHIBITORS OF C-FMS KINASE

  摘要：

  该发明涉及以下式I的化合物： 其中Z、X、J、R2和W如规范中所述，以及其溶剂化合物、水合物、互变异构体和药学上可接受的盐，能够抑制蛋白酪氨酸激酶，特别是c-fms激酶。本发明还提供了治疗自身免疫疾病；以及伴有炎症成分的疾病；治疗卵巢癌、子宫癌、乳腺癌、前列腺癌、肺癌、结肠癌、胃癌、毛细胞白血病的转移；以及治疗疼痛，包括肿瘤转移或骨关节炎引起的骨骼疼痛，或内脏、炎症和神经源性疼痛；以及骨质疏松症、帕盖特病和其他骨吸收介导发病率的疾病，包括类风湿性关节炎和其他形式的炎症性关节炎、骨关节炎、假体失败、溶骨性肉瘤、骨髓瘤和肿瘤转移至骨骼的方法，其中使用了式I的化合物。

  公开号：

  US20090105296A1
• 作为产物：
  描述：

  ethyl,4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate 在 氢氧化钾 、 水 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以90%的产率得到4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt
  参考文献：
  名称：

  氰基取代的 2-羧基咪唑：4-氰基-1-{[2-(三甲基甲硅烷基)乙氧基]甲基}-1H-咪唑-2-羧酸钾盐的合成

  摘要：

  报道了单氰基取代的2-羧基咪唑的第一个例子。4-cyano-1-{[2-(trimethylsilyl)ethoxy]methyl} -1 H-imidazole-2-carboxylate (2) 的合成证明，其中羧酸根基团是通过 SEM- 上的溴-镁交换引入的保护氰基咪唑，然后与氰基甲酸乙酯反应。该合成包括平衡 SEM 保护的咪唑的区域异构混合物以产生单一产物。

  DOI：

  10.1055/s-0028-1083173
• 作为试剂：
  描述：

  5-(4-amino-3-cyclohept-1-enyl-phenyl)-1,3-dimethyl-tetrahydro-pyrimidin-2-one 在 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 生成 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-cyclohept-1-enyl-4-(1,3-dimethyl-2-oxo-hexahydro-pyrimidin-5-yl)-phenyl]-amide
  参考文献：
  名称：

  Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors

  摘要：

  During efforts to improve the bioavailability of FMS kinase inhibitors 1 and 2, a series of saturated and aromatic 4-heterocycles of reduced basicity were prepared and evaluated in an attempt to also improve the cardiovascular safety profile over lead arylamide 1, which possessed ion channel activity. The resultant compounds retained excellent potency and exhibited diminished ion channel activity. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.05.013

文献信息

• SYNERGISTIC MODULATION OF FLT3 KINASE USING A FLT3 INHIBITOR AND A FARNESYL TRANSFERASE INHIBITOR
  申请人：Baumann Andrew Christian

  公开号：US20060281788A1

  公开（公告）日：2006-12-14

  The invention is directed to a method of inhibiting FLT3 tyrosine kinase activity or expression or reducing FLT3 kinase activity or expression in a cell or a subject comprising the administration of a farnesyl transferase inhibitor and a FLT3 kinase inhibitor selected from compounds of Formula I′: Included within the present invention is both prophylactic and therapeutic methods for treating a subject at risk of (or susceptible to) developing a cell proliferative disorder or a disorder related to FLT3.

  本发明涉及一种抑制FLT3酪氨酸激酶活性或表达或减少细胞或受试者中FLT3激酶活性或表达的方法，包括管理法尼基转移酶抑制剂和从公式I'的化合物中选择的FLT3激酶抑制剂。 本发明包括用于治疗处于发展细胞增殖障碍或与FLT3相关障碍风险（或易感性）的受试者的预防和治疗方法。
• METHOD OF INHIBITING C-KIT KINASE
  申请人：Illig R. Carl

  公开号：US20080051402A1

  公开（公告）日：2008-02-28

  A method of reducing or inhibiting kinase activity of C-KIT in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to C-KIT using a compound of the present invention: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.

  本发明提供了一种减少或抑制细胞或主体中C-KIT激酶活性的方法，以及使用本发明的化合物预防或治疗主体中的细胞增殖障碍和/或与C-KIT相关疾病的应用：或其溶剂化物、水合物、互变异构体或药用可接受盐。本发明进一步涉及治疗癌症和其他细胞增殖障碍等条件的方法。
• [EN] SUBSTITUTED PYRIDINE DERIVATIVES USEFUL AS C-FMS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDINE SUBSTITUÉS UTILES EN TANT QU'INHIBITEURS DE KINASE C-FMS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2014151258A1

  公开（公告）日：2014-09-25

  The present invention is directed to substituted pyridine derivatives, pharmaceutical compositions containing said derivatives and the use of said derivatives in the treatment of disorders mediated by c-fms kinase. The present invention is further directed to a process for the preparation of said substituted pyridine derivatives.

  本发明涉及取代吡啶衍生物，含有该衍生物的药物组合物，以及在治疗由c-fms激酶介导的疾病中使用该衍生物。本发明还涉及一种制备所述取代吡啶衍生物的方法。
• C-fms kinase inhibitors
  申请人：Player R. Mark

  公开号：US20050131022A1

  公开（公告）日：2005-06-16

  The invention is directed to compounds of Formulae I: wherein A, R 1 , R 2 , R 3 , R 4 , X, and W are set forth in the specification, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase.

  该发明涉及以下式I的化合物：其中A、R1、R2、R3、R4、X和W如规范中所述，以及其溶剂合物、水合物、互变体或药学上可接受的盐，可以抑制蛋白酪氨酸激酶，尤其是c-fms激酶。
• Inhibitors of c-fms kinase
  申请人：Illig R. Carl

  公开号：US20060100201A1

  公开（公告）日：2006-05-11

  The invention relates to compounds of Formula I: wherein A, X, R 2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.

  本发明涉及公式I的化合物：其中A、X、R2和W在说明书中设置，以及其溶剂化物、水合物、互变异构体和药学上可接受的盐，它们抑制蛋白酪氨酸激酶，特别是c-fms激酶。本发明还提供了利用公式I的化合物治疗自身免疫性疾病和具有炎症成分的疾病；治疗卵巢癌、子宫癌、乳腺癌、结肠癌、胃癌、毛细胞白血病和非小细胞肺癌的转移；以及治疗疼痛，包括肿瘤转移或骨关节炎引起的骨骼疼痛，或内脏、炎症和神经性疼痛；以及骨质疏松症、Paget病和其他骨吸收介导的疾病，包括关节炎、假体失效、骨溶性肉瘤、骨髓瘤和肿瘤转移至骨骼。