5-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(R)-(+)-(2,2-dimethyl-[1,3]dioxolane-4-carbonyl)-piperidin-4-yl]-phenyl}-amide | 885693-41-4

• 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: 5-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(R)-(+)-(2,2-dimethyl-[1,3]dioxolane-4-carbonyl)-piperidin-4-yl]-phenyl}-amide
• 英文别名: 5-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(R)-(+)(2,2-dimethyl-[1,3]dioxolane-4-carbonyl)-piperidin-4-yl]-phenyl}-amide；5-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(R)-(2,2-dimethyl-[1,3]dioxolane-4-carbonyl)-piperidin-4-yl]-phenyl}-amide；5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[(4R)-2,2-dimethyl-1,3-dioxolane-4-carbonyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide
• CAS: 885693-41-4
• 化学式: C₂₈H₃₃N₅O₄
• 分子量: 503.601
• InChiKey: CBKRUYNSGZESDZ-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(R)-(+)-(2,2-dimethyl-[1,3]dioxolane-4-carbonyl)-piperidin-4-yl]-phenyl}-amide 在 盐酸 、 甲醇 、 水 作用下， 反应 28.0h， 以52%的产率得到5-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-((R)-(+)-2,3-dihydroxy-propionyl)-piperidin-4-yl]-phenyl}-amide
  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
• 作为产物：
  描述：

  1-BOC-4-(4-氨基苯基)哌啶 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 乙醇 、 sodium carbonate 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 19.58h， 生成 5-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(R)-(+)-(2,2-dimethyl-[1,3]dioxolane-4-carbonyl)-piperidin-4-yl]-phenyl}-amide
  参考文献：
  名称：

  Optimization of a Potent Class of Arylamide Colony-Stimulating Factor-1 Receptor Inhibitors Leading to Anti-inflammatory Clinical Candidate 4-Cyano-N-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1H-imidazole-2-carboxamide (JNJ-28312141)

  摘要：

  A class of potent inhibitors of colony-stimulating factor-1 receptor (CSF-1R or FMS), as exemplified by 8 and 21, was optimized to improve pharmacokinetic and pharmacodynamic properties and potential toxicological liabilities. Early stage absorption, distribution, metabolism, and excretion assays were employed to ensure the incorporation of druglike properties resulting in the selection of several compounds with good activity in a pharmacodynamic screening assay in mice. Further investigation, utilizing the type II collagen-induced arthritis model in mice, culminated in the selection of anti-inflammatory development candidate JNJ-28312141 (23, FMS IC50 = 0.69 nM, cell assay IC50 = 2.6 nM). Compound 23 also demonstrated efficacy in rat adjuvant and streptococcal cell wall-induced models of arthritis and has entered phase I clinical trials.

  DOI：

  10.1021/jm200900q

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。
• 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：——
• Optimization of a Potent Class of Arylamide Colony-Stimulating Factor-1 Receptor Inhibitors Leading to Anti-inflammatory Clinical Candidate 4-Cyano-<i>N</i>-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1<i>H</i>-imidazole-2-carboxamide (JNJ-28312141)
  作者：Carl R. Illig、Carl L. Manthey、Mark J. Wall、Sanath K. Meegalla、Jinsheng Chen、Kenneth J. Wilson、Shelley K. Ballentine、Renee L. DesJarlais、Carsten Schubert、Carl S. Crysler、Yanmin Chen、Christopher J. Molloy、Margery A. Chaikin、Robert R. Donatelli、Edward Yurkow、Zhao Zhou、Mark R. Player、Bruce E. Tomczuk

  DOI：10.1021/jm200900q

  日期：2011.11.24

  A class of potent inhibitors of colony-stimulating factor-1 receptor (CSF-1R or FMS), as exemplified by 8 and 21, was optimized to improve pharmacokinetic and pharmacodynamic properties and potential toxicological liabilities. Early stage absorption, distribution, metabolism, and excretion assays were employed to ensure the incorporation of druglike properties resulting in the selection of several compounds with good activity in a pharmacodynamic screening assay in mice. Further investigation, utilizing the type II collagen-induced arthritis model in mice, culminated in the selection of anti-inflammatory development candidate JNJ-28312141 (23, FMS IC50 = 0.69 nM, cell assay IC50 = 2.6 nM). Compound 23 also demonstrated efficacy in rat adjuvant and streptococcal cell wall-induced models of arthritis and has entered phase I clinical trials.