4-氰基-4-(3,4-二甲氧基苯基)-5-甲基己酸 | 36622-23-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氰基-4-(3,4-二甲氧基苯基)-5-甲基己酸
• 英文名称: 4-cyano-4-(3,4-dimethoxyphenyl)-5-methyl hexanoic acid
• 英文别名: 4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhexanoic acid
• CAS: 36622-23-8
• 化学式: C₁₆H₂₁NO₄
• 分子量: 291.347
• InChiKey: BSHCLIANLKRGLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  79.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氰基-4-(3,4-二甲氧基苯基)-5-甲基己酸 在 草酰氯 作用下， 以 氯仿 、 苯 为溶剂， 反应 12.0h， 生成 Anthracene-9-carboxylic acid 3-(tert-butoxycarbonyl-{3-[4-cyano-4-(3,4-dimethoxy-phenyl)-5-methyl-hexanoyloxy]-propyl}-amino)-propyl ester
  参考文献：
  名称：

  Exploratory Chemistry toward the Identification of a New Class of Multidrug Resistance Reverters Inspired by Pervilleine and Verapamil Models

  摘要：

  On the basis of the present knowledge of the substrate recognition site of ABC transporter proteins and inspired by the structures of verapamil and pervilleine A, a new class of Pgp-mediated multidrug resistance (MDR) reverters has been designed and synthesized. The new compounds are flexible molecules carrying one or two basic nitrogen atoms flanked, at properly modulated distance, by two aromatic moieties. Most of the molecules studied possess MDR inhibitory activity on anthracycline-resistant erythroleukemia K 562 cells, showing a potency that is higher than that of the reference compound verapamil and, in a few cases (7, 12, 13, 17, 20, 22, 28), is in the high nanomolar range. These compounds may be useful leads to develop new MDR reverting agents. In fact, the chemical structure of the class is fairly simple and can be implemented in a variety of ways that will allow the synthesis of new compounds that might be useful leads for the development of drugs to control Pgp-dependent MDR.

  DOI：

  10.1021/jm050542x
• 作为产物：
  描述：

  (2S)-(-)-2-(3,4-dimethoxyphenyl)-5-hydroxy-2-isopropylpentanenitrile 在 potassium permanganate 、 四丁基溴化铵 作用下， 以 苯 为溶剂， 反应 12.0h， 以90%的产率得到4-氰基-4-(3,4-二甲氧基苯基)-5-甲基己酸
  参考文献：
  名称：

  设计，合成和初步药理学评估的4-氨基哌啶衍生物作为N型钙通道阻滞剂，对疼痛和神经性疼痛有活性。

  摘要：

  已经合成了几种具有4-氨基哌啶骨架的化合物，它们在两个氮原子上都被包含维拉帕米和氟那利嗪的结构基序的烷基或酰基部分修饰，以及在已知的N型钙通道拮抗剂中更常见的那些。使用小鼠热板试验的抗伤害感受活性来选择要进一步研究的分子。在PC12大鼠嗜铬细胞瘤克隆细胞系上对活性化合物进行了体外测试，以评估其对N型钙通道和神经性疼痛大鼠模型的作用。已选择了两种具有N型钙通道拮抗作用且对疼痛和神经性疼痛具有有效作用的化合物（3和18）进行进一步研究。

  DOI：

  10.1021/jm049923l

文献信息

• NITRILE DERIVATIVES
  申请人：Eisai Co., Ltd.

  公开号：EP1167348A1

  公开（公告）日：2002-01-02

  The present invention provides a novel nitrile compound useful as an intermediate for the production of, for example, N,N-substituted cyclic amine derivatives or phenylacetonitrile derivatives that are useful as a medicine. Specifically it provides a nitrile carboxylic acid compound, nitrile ester compound and nitrile alcohol compound. That is, it provides a nitrile compound represented by the following formula (I): wherein R1 and R2 means substituents; m means 0 or an integer of from 1 to 6; n means 0 or an integer of from 1 to 5; and R3 means carboxyl group, a lower alkoxycarbonyl group or hydroxymethyl group.

  本发明提供了一种新型腈化合物，可用作生产N,N-取代环胺衍生物或苯乙腈衍生物的中间体，这些衍生物可用作药物。具体而言，它提供了一种腈羧酸化合物、腈酯化合物和腈醇化合物。即提供了由以下式（I）表示的腈化合物：其中R1和R2表示取代基；m表示0或1至6之间的整数；n表示0或1至5之间的整数；R3表示羧基、较低的烷氧羰基或羟甲基基团。
• Compound and process
  申请人：Darwin Discovery Limited

  公开号：US05859279A1

  公开（公告）日：1999-01-12

  A process for the preparation of a compound of formula (VI), optionally in enantiomerically-enriched form (R or S), comprises chemoselective reduction of a novel compound of formula (V), wherein Ar.sup.1 and Ar.sup.2 are independently selected from optionally-substituted aromatic or heteroaromatic groups having upto 20 C atoms, Ak is C.sub.1-20 alkyl, and R is H or C.sub.1-20 alkyl. ##STR1##

  一种制备化合物公式（VI）的方法，可选地以对映体富集的形式（R或S），包括化学选择性还原公式（V）的新化合物，其中Ar.sup.1和Ar.sup.2分别选择具有最多20个C原子的可选取代芳香族或杂环芳香族基团，Ak为C.sub.1-20烷基，R为H或C.sub.1-20烷基。##STR1##
• A Scaleable Route to the Pure Enantiomers of Verapamil
  作者：Robin M. Bannister、Michael H. Brookes、Graham R. Evans、Ruth B. Katz、Nicholas D. Tyrrell

  DOI：10.1021/op000059q

  日期：2000.11.1

  A versatile route to single enantiomer verapamil from readily available raw materials is described. The key intermediate, 4-cyano-4-(3,4-dimethoxyphenyl)-5-methyl hexanoic acid (verapamilic acid), was resolved efficiently with α-methyl benzylamine. Stereochemical integrity at the quarternary carbon centre was preserved through subsequent steps to give either (R)-or (S)-verapamil in good overall yield

  描述了从容易获得的原材料中获得单一对映异构体维拉帕米的通用途径。关键中间体 4-氰基-4-(3,4-二甲氧基苯基)-5-甲基己酸（维拉帕米酸）用 α-甲基苄胺有效分离。四元碳中心的立体化学完整性通过随后的步骤得以保持，从而以良好的总产率提供 (R)-或 (S)-维拉帕米。该序列结合了选择性硼烷介导的叔酰胺还原。已经成功地证明了解决步骤的过程放大到中试工厂。
• New structure–activity relationship studies in a series of N,N-bis(cyclohexanol)amine aryl esters as potent reversers of P-glycoprotein-mediated multidrug resistance (MDR)
  作者：Francesca Orlandi、Marcella Coronnello、Cristina Bellucci、Silvia Dei、Luca Guandalini、Dina Manetti、Cecilia Martelli、Maria Novella Romanelli、Serena Scapecchi、Milena Salerno、Hayette Menif、Ivan Bello、Enrico Mini、Elisabetta Teodori

  DOI：10.1016/j.bmc.2012.11.019

  日期：2013.1

  As a continuation of previous research on a new series of potent and efficacious P-gp-dependent multidrug resistant (MDR) reversers with a N,N-bis(cyclohexanol) amine scaffold, we have designed and synthesized several analogs by modulation of the two aromatic moieties linked through ester functions to the N,N-bis(cyclohexanol) amine, aiming to optimize activity and to extend structure-activity relationships (SAR) within the series. This scaffold, when esterified with two different aromatic carboxylic acids, gives origin to four geometric isomers (cis/trans, trans/trans, cis/cis and trans/cis).The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Most of them resulted in being potent modulators of the extrusion pump P-gp, showing potency values ([I](0.5)) in the submicromolar and nanomolar range. Of these, compounds 2b, 2c, 3d, 5a-d and 6d, showed excellent efficacy with a alpha(max) close to 1. Selected compounds (2d, 3a, 3b, 5a-d) were further studied to evaluate their doxorubicin cytotoxicity potentiation (RF) on doxorubicin-resistant erythroleukemia K562 cells and were found able to enhance significantly doxorubicin cytotoxicity on K562/DOX cells.The results of both pirarubicin uptake and the cytotoxicity assay, indicate that the new compounds of the series are potent P-gp-mediated MDR reversers. They present a structure with a mix of flexible and rigid moieties, a property that seems critical to allow the molecules to choose the most productive of the several binding modes possible in the transporter recognition site.In particular, compounds 5c and 5d, similar to the already reported analogous isomers 1c and 1d,(29) are potent and efficacious modulators of P-gp-dependent MDR and may be promising leads for the development of MDR-reversal drugs. (C) 2012 Elsevier Ltd. All rights reserved.
• RACEMISATION OF QUATERNARY CHIRAL CENTERS
  申请人：Darwin Discovery Limited

  公开号：EP0880497A1

  公开（公告）日：1998-12-02