4-[5-(2-hydroxyethyl)imidazol-1-ylmethyl]benzonitrile | 186202-60-8

• 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-[5-(2-hydroxyethyl)imidazol-1-ylmethyl]benzonitrile
• 英文别名: 4-{[5-(2-hydroxyethyl)-1H-imidazol-1-yl]methyl}benzonitrile；3-(4-cyanobenzyl)-3H-imidazol-4-ylethyl alcohol；4-[[5-(2-hydroxyethyl)imidazol-1-yl]methyl]benzonitrile
• CAS: 186202-60-8
• 化学式: C₁₃H₁₃N₃O
• 分子量: 227.266
• InChiKey: JZDNPKOWZGSKAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[5-(2-hydroxyethyl)imidazol-1-ylmethyl]benzonitrile 在 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 4-{5-[2-((R)-1-Benzyl-2-oxo-pyrrolidin-3-ylamino)-ethyl]-imidazol-1-ylmethyl}-benzonitrile
  参考文献：
  名称：

  Design and Biological Activity of (S)-4-(5-{[1-(3-Chlorobenzyl)-2- oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile, a 3-Aminopyrrolidinone Farnesyltransferase Inhibitor with Excellent Cell Potency

  摘要：

  The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-amino-pyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.

  DOI：

  10.1021/jm010156p
• 作为产物：
  描述：

  [1-(4-Cyanobenzyl)-1H-imidazol-5-yl]acetic acid methyl ester 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以50%的产率得到4-[5-(2-hydroxyethyl)imidazol-1-ylmethyl]benzonitrile
  参考文献：
  名称：

  Design and Biological Activity of (S)-4-(5-{[1-(3-Chlorobenzyl)-2- oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile, a 3-Aminopyrrolidinone Farnesyltransferase Inhibitor with Excellent Cell Potency

  摘要：

  The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-amino-pyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.

  DOI：

  10.1021/jm010156p

文献信息

• Dihydro-2h-napthalene-1-one inhibitors of ras farnesyl transferase
  申请人：——

  公开号：US20030232790A1

  公开（公告）日：2003-12-18

  The present invention provides dihydro-2H-napthalene-1-ones of formula (V), and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, which are useful for treating and preventing uncontrolled or abnormal proliferation of tissues, such as cancer, atherosclerosis, restenosis, and psoriasis. Specifically, the present invention relates to compounds that inhibit the farnesyl transferase enzyme. 1

  本发明提供了式（V）的二氢-2H-萘酮，以及其药学上可接受的盐、酯、酰胺和前药，用于治疗和预防组织的不受控制或异常增殖，如癌症、动脉粥样硬化、再狭窄和牛皮癣。具体而言，本发明涉及抑制法尼基转移酶酶的化合物。
• Dihydro-2H-naphthalene-1-one inhibitors of ras farnesyl transferase
  申请人：——

  公开号：US20040171844A1

  公开（公告）日：2004-09-02

  Disclosed are compounds of the Formula I 1 wherein: R a , R b , and R c are the same or different and represent hydrogen, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted arylalkyl, or unsubstituted heteroarylalkyl; R 1 and R 2 are the same or different and represent hydrogen, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted arylalkyl, or unsubstituted heteroarylalkyl; n is 0, 2, or 3, provided that when the imidazole is attached at the imidazole nitrogen to (CR a R b ) n and Y is O, NR c , or S, then n is not 0; Y is NR c , O, —CHR c , or S; and R 3 is unsubstituted aryl, unsubstituted heteroarylalkyl or unsubstituted arylalkyl. The present invention also provides a pharmaceutically acceptable composition that comprises a compound of Formula I. The present invention also provides a method of treating or preventing restenosis, atherosclerosis or cancer, the method comprising administering to a patient having restenosis, atherosclerosis or cancer, or at risk of having restenosis, atherosclerosis or cancer, a therapeutically effective amount of Formula I. Also provided is a method of treating or preventing restenosis or atherosclerosis, or treating cancer, the method of comprising administering to a patient having restenosis or atherosclerosis, or at risk of having restenosis or atherosclerosis, or having cancer a therapeutically effective amount of a compound of Formula I.

  公开了式I1的化合物，其中：Ra，Rb和Rc相同或不同，代表氢，（C1-C6）-烷基，（C2-C6）-烯基，未取代芳基，未取代杂环芳基，未取代芳基烷基或未取代杂环芳基烷基；R1和R2相同或不同，代表氢，（C1-C6）-烷基，（C2-C6）-烯基，未取代芳基，未取代杂环芳基，未取代芳基烷基或未取代杂环芳基烷基；n为0、2或3，但当咪唑连接在咪唑氮上，并且Y为O、NRc或S时，n不为0；Y为NRc、O、—CHRc或S；且R3为未取代芳基、未取代杂环芳基烷基或未取代芳基烷基。本发明还提供了一种药学上可接受的组合物，其包括式I的化合物。本发明还提供了一种治疗或预防再狭窄、动脉粥样硬化或癌症的方法，该方法包括向患有再狭窄、动脉粥样硬化或癌症或有再狭窄、动脉粥样硬化或癌症风险的患者，或者向患有再狭窄或动脉粥样硬化或有再狭窄或动脉粥样硬化风险的患者，或者向患有癌症的患者，给予式I的化合物的治疗有效量。还提供了一种治疗或预防再狭窄或动脉粥样硬化，或治疗癌症的方法，该方法包括向患有再狭窄或动脉粥样硬化或有再狭窄或动脉粥样硬化风险的患者或患有癌症的患者，给予式I的化合物的治疗有效量。
• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05891889A1

  公开（公告）日：1999-04-06

  The present invention is directed to compounds which inhibit farnesyl-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 farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

  本发明涉及抑制法尼酰-蛋白转移酶（FTase）和致癌基因蛋白Ras的法尼酰化的化合物。本发明还涉及包含本发明化合物的化学治疗组合物以及抑制法尼酰-蛋白转移酶和致癌基因蛋白Ras的法尼酰化的方法。
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：EP0833633A1

  公开（公告）日：1998-04-08
• EP0833633A4
  申请人：——

  公开号：EP0833633A4

  公开（公告）日：1999-03-24