1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride

• 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: 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride
• 英文别名: 1H-Imidazolium, 1,3-bis[2,6-bis(1-methylethyl)phenyl]-, chloride；1,3-bis[2,6-di(propan-2-yl)phenyl]-1,2-dihydroimidazol-1-ium;chloride
• 化学式: C₂₇H₃₈N₂*ClH
• 分子量: 427.073
• InChiKey: BPPGPFOTTDXLDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.36
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  6.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 1,3-双(2,6-二异丙基苯基)咪唑-2-烯
  参考文献：
  名称：

  定义明确的NHC-铁配合物催化选择性酯化为醛

  摘要：

  在直接接触醛的过程中：在紫外线照射下，由定义明确的N-杂环-卡宾-铁络合物催化的氢化硅烷化作用使酯选择性地还原为醛（参见方案； Bn =苄基，Mes =间苯二甲酰）。低的催化剂负载量和非常温和的反应条件使这种化学选择性转化成为用二异丁基氢化铝还原酯的有前途的替代方法。

  DOI：

  10.1002/anie.201303003
• 作为产物：
  描述：

  1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride
  参考文献：
  名称：

  Separation, recovery and reuse of N-heterocyclic carbene catalysts in transesterification reactions

  摘要：

  开发了一种新颖且便捷的策略，用于分离、回收并再利用转酯化反应中的N-杂环卡宾催化剂。

  DOI：

  10.1039/b910162d
• 作为试剂：
  描述：

  甲基丁胺 、 1-氟萘 在 bis(1,5-cyclooctadiene)nickel (0) 、 sodium t-butanolate 、 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以46%的产率得到N-butyl-N-methylnaphthalen-1-amine
  参考文献：
  名称：

  镍催化的氟代芳烃和胺的偶联

  摘要：

  AbstractThe combination of bis(cyclooctadiene)nickel [Ni(COD)2] and 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene hydrochloride (IPr⋅HCl) effectively catalyzes coupling of fluoroarenes with amines in the presence of sodium tert‐butoxide (t‐BuONa). Activated, unactivated and deactivated fluoroarenes as well as fluoropyridines can react with cyclic or acyclic aliphatic amines. The reactions tolerate various functional groups in the fluorides including PhC(O), C(O)NEt2, CF3, OMe and vinyl groups.magnified image

  DOI：

  10.1002/adsc.201300485

文献信息

• Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20150307465A1

  公开（公告）日：2015-10-29

  In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 9 , ring A, ring B, m, n, p, -L 1 -, -L 2 -, and -L 3 - is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (“Aβ”) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's disease, are also disclosed.

  本发明提供了多种形式的亚氨基噻二唑二氧化物化合物，包括公式(I)的化合物： 包括它们的立体异构体，以及所述立体异构体的药用可接受盐，其中R1、R2、R3、R4、R5、R9、环A、环B、m、n、p、-L1-、-L2-和-L3-都是独立选择且按本文定义。发明的新型亚氨基噻二唑二氧化物化合物出人意料地被发现具有预期的特性，使其作为BACE抑制剂以及/或用于治疗和预防与β-淀粉样蛋白（“Aβ”）生成相关的各种病理学具有优势。还公开了包含一个或多个此类化合物（单独使用和与一个或多个其他活性成分组合使用）的药物组合物，以及它们的制备方法和用于治疗与淀粉样β（Aβ）蛋白相关的病理学，包括阿尔茨海默病的方法。
• Inhibitors of Bruton's Tyrosine Kinase
  申请人：Berthel Steven

  公开号：US20100222325A1

  公开（公告）日：2010-09-02

  This application discloses 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-Phenyl-1H-pyrazin-2-one derivatives according to generic Formulae I-III: wherein, variables Q, R, X, X′, Y 1 , Y 2 , Y 2′ , Y 3 , Y 4 , Y 5 , m, and n are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formulae I-III and at least one carrier, diluent or excipient.

  该应用程序根据通用公式I-III披露了5-苯基-1H-吡啶-2-酮，6-苯基-2H-吡啶-3-酮和5-苯基-1H-吡嗪-2-酮衍生物： 其中，变量Q、R、X、X'、Y1、Y2、Y2'、Y3、Y4、Y5、m和n的定义如本文所述，这些化合物抑制Btk。本文披露的化合物对调节Btk的活性并治疗与过度Btk活性相关的疾病有用。这些化合物进一步有助于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，如类风湿性关节炎。还披露了含有公式I-III化合物和至少一种载体、稀释剂或赋形剂的组合物。
• Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors
  申请人：Buck A. Elizabeth

  公开号：US20070280928A1

  公开（公告）日：2007-12-06

  The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA®).

  本发明提供了一种治疗患者体内NSCL、胰腺、结肠或乳腺癌肿瘤或肿瘤转移的方法，包括向患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物的组合，其中该药物是mTOR抑制剂，可以附加其他药物或治疗，如其他抗癌药物或放射治疗。本发明还提供了一种治疗患者体内肿瘤或肿瘤转移的方法，包括向患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物的组合，其中该药物是一种能够结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。本发明还提供了一种制药组合物，包括一种能够结合并直接抑制mTORC1和mTORC2激酶的EGFR激酶抑制剂和mTOR抑制剂，以及一种药用载体。本发明中可用于实施该方法的EGFR激酶抑制剂的首选示例是化合物厄洛替尼盐酸盐（也称为TARCEVA®）。
• [EN] 6,6-BICYCLIC RING SUBSTITUTED HETEROBICYCLIC PROTEIN KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTEINE KINASE HETEROBICYCLIQUES A SUBSTITUTION DE NOYAU BICYCLIQUE 6,6
  申请人：OSI PHARM INC

  公开号：WO2005097800A1

  公开（公告）日：2005-10-20

  Compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein XI, X2, X3, X4, X5, X6, X7, R1, and Q1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer, inflammation, psoriasis, allergy/asthma, disease and conditions of the immune system, disease and conditions of the central nervous system.

  该式(I)的化合物及其药用可接受的盐，其中XI、X2、X3、X4、X5、X6、X7、R1和Q1在此处定义，抑制IGF-1R酶，可用于治疗和/或预防高增殖性疾病，如癌症、炎症、牛皮癣、过敏/哮喘、免疫系统疾病和疾病及中枢神经系统疾病和状况。
• Selective Reduction of Esters to Aldehydes under the Catalysis of Well-Defined NHC-Iron Complexes
  作者：Haoquan Li、Luis C. Misal Castro、Jianxia Zheng、Thierry Roisnel、Vincent Dorcet、Jean-Baptiste Sortais、Christophe Darcel

  DOI：10.1002/anie.201303003

  日期：2013.7.29

  a direct course to the aldehyde: Hydrosilylation catalyzed by a well‐defined N‐heterocyclic‐carbene–iron complex under UV irradiation enabled the selective reduction of esters to aldehydes (see scheme; Bn=benzyl, Mes=mesityl). The low catalyst loading and very mild reaction conditions make this chemoselective transformation a promising alternative to the reduction of esters with diisobutylaluminum

  在直接接触醛的过程中：在紫外线照射下，由定义明确的N-杂环-卡宾-铁络合物催化的氢化硅烷化作用使酯选择性地还原为醛（参见方案； Bn =苄基，Mes =间苯二甲酰）。低的催化剂负载量和非常温和的反应条件使这种化学选择性转化成为用二异丁基氢化铝还原酯的有前途的替代方法。