2-Fluoro-4-[hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-benzonitrile | 222978-26-9

• 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: 2-Fluoro-4-[hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-benzonitrile
• 英文别名: 2-fluoro-4-[hydroxy(1-methyl-1H-imidazol-5-yl)methyl]benzonitrile；(3-fluoro-4-cyanophenyl)-(3-methyl-3H-imidazol-4-yl)methanol；2-fluoro-4-(hydroxy(1-methyl-1H-imidazol-5-yl)methyl)benzonitrile；2-fluoro-4-[hydroxy-(3-methylimidazol-4-yl)methyl]benzonitrile
• CAS: 222978-26-9
• 化学式: C₁₂H₁₀FN₃O
• 分子量: 231.229
• InChiKey: BZNJXCYKMJUEKY-UHFFFAOYSA-N

物化性质

• 沸点：
  481.4±45.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Fluoro-4-[hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-benzonitrile 在 盐酸 、 manganese(IV) oxide 、 titanium(IV) tetraethanolate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 76.0h， 生成 (+)-4-[1-amino-1-(3-methyl-3H-imidazol-4-yl)-ethyl]-2-fluoro-benzonitrile
  参考文献：
  名称：

  Asymmetric synthesis of α,α-diaryl and α-aryl-α-heteroaryl alkylamines by organometallic additions to N-tert- butanesulfinyl ketimines

  摘要：

  Organometallic addition to tert-butanesufinyl ketimines derived from diaryl and aryl-heteroaryl ketones provided the corresponding alpha,alpha -diaryl and alpha -aryl-alpha -heteroaryl alkylamines in good yield with high diastereoselectivity. In many cases, imine facial selectivity is reversed on changing the organometallic counterion. (C) 2001 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(01)01513-1
• 作为产物：
  描述：

  2-氟-4-甲酰基苯甲腈 在 吡啶 、 甲醇 、 sodium hydroxide 、 乙基溴化镁 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 2-Fluoro-4-[hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-benzonitrile
  参考文献：
  名称：

  双蛋白法呢基转移酶-香叶基香叶基转移酶-I抑制剂可作为潜在的癌症化学治疗剂。

  摘要：

  一系列新的二芳基醚内酰胺已被确定为非常有效的蛋白法呢基转移酶（FTase）和蛋白geranylgeranyltransferase I（GGTase-I）的双重抑制剂，这些酶涉及Ras的烯丙基化。这些化合物之一与FTase之间形成的配合物的结构已通过X射线晶体学确定。这些化合物是第一个被报道在体内抑制重要癌基因Ki-Ras4B异戊二烯化的化合物。不幸的是，足以达到该终点的剂量迅速致死。

  DOI：

  10.1021/jm020587n

文献信息

• Method of treating cancer
  申请人：——

  公开号：US20030220241A1

  公开（公告）日：2003-11-27

  The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase. The invention also relates to methods of preparing such compositions.

  本发明涉及使用一种PSA共轭物和一种前脂蛋白转移酶抑制剂的组合治疗癌症的方法，该方法包括向所述哺乳动物施用来自以下组中选择的至少两种治疗剂的量，所述组包括一种PSA共轭物和一种前脂蛋白转移酶抑制剂，所述治疗剂可以顺序给药或同时给药。该发明还涉及制备这种组合物的方法。
• Farnesyltransferase inhibitors
  申请人：——

  公开号：US20030087940A1

  公开（公告）日：2003-05-08

  Substituted imidazoles and thiazoles having the formula 1 are useful for inhibiting farnesyltransferase. Also disclosed are farnesyltransferase-inhibiting compositions and methods of inhibiting farnesyltransferase in a patient.

  具有以下化学式的取代咪唑和噻唑对抑制法尼基转移酶具有用处。还公开了抑制法尼基转移酶的组合物和在患者中抑制法尼基转移酶的方法。
• Inhibitors of prenyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US06297239B1

  公开（公告）日：2001-10-02

  The present invention is directed to compounds which inhibit a prenyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting a prenyl-protein transferase and the prenylation of the oncogene protein Ras.

  本发明涉及抑制前脂蛋白转移酶（FTase）和致癌基因蛋白Ras的法尼醇化的化合物。该发明进一步涉及含有本发明化合物的化疗组合物以及抑制前脂蛋白转移酶和致癌基因蛋白Ras的方法。
• Design, Synthesis, and Biological Activity of 4-[(4-Cyano-2-arylbenzyloxy)-(3-methyl-3<i>H</i>-imidazol-4-yl)methyl]benzonitriles as Potent and Selective Farnesyltransferase Inhibitors
  作者：Le Wang、Gary T. Wang、Xilu Wang、Yunsong Tong、Gerry Sullivan、David Park、Nicholas M. Leonard、Qun Li、Jerry Cohen、Wen-Zhen Gu、Haiying Zhang、Joy L. Bauch、Clarissa G. Jakob、Charles W. Hutchins、Vincent S. Stoll、Kennan Marsh、Saul H. Rosenberg、Hing L. Sham、Nan-Horng Lin

  DOI：10.1021/jm030434f

  日期：2004.1.1

  synthesized as selective farnesyltransferase inhibitors using structure-based design. X-ray cocrystal structures of compound 20-FTase-HFP and A313326-FTase-HFP confirmed our initial design. The decreased interaction between the aryl groups and Ser 48 in GGTase-I binding site could be one possible reason to explain the improved selectivity for this new series of FTase inhibitors. Medicinal chemistry efforts

  已经使用基于结构的设计合成了一系列新型的4-[（4-氰基-2-芳基苄氧基）-（3-甲基-3H-咪唑-4-基）甲基]苄腈作为选择性的法呢基转移酶抑制剂。化合物20-FTase-HFP和A313326-FTase-HFP的X射线共晶体结构证实了我们的初步设计。在GGTase-I结合位点中，芳基与Ser 48之间相互作用的减少可能是解释这种新系列FTase抑制剂选择性提高的可能原因。药物化学作用导致发现了具有强细胞活性（EC（50）= 3.5 nM）和杰出的药代动力学特征的化合物64（生物利用度96％，口服t（1/2）为18.4 h，0.19 L /（hx） kg）血浆清除率）。
• [EN] A METHOD OF TREATING CANCER<br/>[FR] UNE METHODE POUR LE TRAITEMENT DU CANCER
  申请人：MERCK & CO INC

  公开号：WO2000059930A1

  公开（公告）日：2000-10-12

  The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a compound which is an inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a compound which is an inhibitor of prenyl-protein transferase. The invention also relates to methods of preparing such compositions.

  本发明涉及使用一种PSA共轭物和一种前尼基蛋白转移酶抑制剂的组合治疗癌症的方法，该方法包括向哺乳动物施用至少两种治疗剂量，所述治疗剂量从以下组合中选择：一种是PSA共轭物，一种是前尼基蛋白转移酶抑制剂，无论是按顺序或同时施用。本发明还涉及制备这种组合物的方法。