4-[4-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-(1,1-dioxo-1,2,3,6-tetrahydro-1λ⁶-thiopyran-4-yl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester | 885693-13-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[4-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-(1,1-dioxo-1,2,3,6-tetrahydro-1λ⁶-thiopyran-4-yl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 4-[4-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-(1,1-dioxo-1,2,3,6-tetrahydro-1λ6-thiopyran-4-yl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[4-[[4-cyano-1-(2-trimethylsilylethoxymethyl)imidazole-2-carbonyl]amino]-3-(1,1-dioxo-3,6-dihydro-2H-thiopyran-4-yl)phenyl]piperidine-1-carboxylate
• CAS: 885693-13-0
• 化学式: C₃₂H₄₅N₅O₆SSi
• 分子量: 655.891
• InChiKey: XMVQDVBLOPSPMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.64
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  152
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[4-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-(1,1-dioxo-1,2,3,6-tetrahydro-1λ⁶-thiopyran-4-yl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 4-cyano-1H-imidazole-2-carboxylic acid [2-(1,1-dioxo-1,2,3,6-tetrahydro-1λ6-thiopyran-4-yl)-4-piperidin-4-yl-phenyl]-amide
  参考文献：
  名称：

  Structure-based optimization of a potent class of arylamide FMS inhibitors

  摘要：

  An anti-inflammatory 1,2,4-phenylenetriamine-containing series of FMS inhibitors with a potential to form reactive metabolites was transformed into a series with equivalent potency by incorporation of carbon-based replacement groups. Structure-based modeling provided the framework to efficiently effect this transformation and restore potencies to previous levels. This optimization removed a risk factor for potential idiosyncratic drug reactions. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.04.059
• 作为产物：
  描述：

  4-[4-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-(3,6-dihydro-2H-thiopyran-4-yl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester 在 m-chloroperoxybenzoic acid 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以67%的产率得到4-[4-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-(1,1-dioxo-1,2,3,6-tetrahydro-1λ⁶-thiopyran-4-yl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  SYNERGISTIC MODULATION OF FLT3 KINASE USING A FLT3 INHIBITOR AND A FARNESYL TRANSFERASE INHIBITOR

  摘要：

  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。

  公开号：

  US20060281788A1

文献信息

• 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。
• WO2006/47277
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/48088
  申请人：——

  公开号：——

  公开（公告）日：——
• 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。
• Structure-based optimization of a potent class of arylamide FMS inhibitors
  作者：Sanath K. Meegalla、Mark J. Wall、Jinsheng Chen、Kenneth J. Wilson、Shelley K. Ballentine、Renee L. DesJarlais、Carsten Schubert、Carl S. Crysler、Yanmin Chen、Christopher J. Molloy、Margery A. Chaikin、Carl L. Manthey、Mark R. Player、Bruce E. Tomczuk、Carl R. Illig

  DOI：10.1016/j.bmcl.2008.04.059

  日期：2008.6

  An anti-inflammatory 1,2,4-phenylenetriamine-containing series of FMS inhibitors with a potential to form reactive metabolites was transformed into a series with equivalent potency by incorporation of carbon-based replacement groups. Structure-based modeling provided the framework to efficiently effect this transformation and restore potencies to previous levels. This optimization removed a risk factor for potential idiosyncratic drug reactions. (C) 2008 Elsevier Ltd. All rights reserved.