3-(4-benzylpiperidin-1-yl)propanenitrile | 4608-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-(4-benzylpiperidin-1-yl)propanenitrile
• 英文别名: 3-(4-benzylpiperidin-1-yl)propionitrile
• CAS: 4608-82-6
• 化学式: C₁₅H₂₀N₂
• mdl: MFCD11546890
• 分子量: 228.337
• InChiKey: IRDXQRKKLQYXRZ-UHFFFAOYSA-N

物化性质

• 沸点：
  131.5-135.0 °C
• 密度：
  1.022±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.533
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(4-benzylpiperidin-1-yl)propanenitrile 在 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 5.33h， 生成 3-((3-(4-benzylpiperidin-1-yl)propyl)carbamoyl)benzyl nitrate
  参考文献：
  名称：

  Sigma Receptor Ligands Carrying a Nitric Oxide Donor Nitrate Moiety: Synthesis, In Silico, and Biological Evaluation

  摘要：

  We report the development of molecular hybrids in which a nitrate group serving as nitric oxide (NO) donor is covalently joined to sigma receptor ligands to give candidates for double-targeted cancer therapy. The compounds have been evaluated in radioligand binding assay at both sigma receptors and selected compounds tested for NO release. Compounds 9, 15, 18, 19, and 21 were subjected to MTT test. Compound 15 produced a significant reduction of MCF-7 and Caco-2 cellular viability with comparable IC50 as doxorubicin, being also not toxic for fibroblast HFF-1 cells. Compound 15 has shown a sigma(1), receptor antagonist/sigma(2) receptor agonist profile. Two derivatives of compound 15 lacking the nitrate group did not induce a reduction of MCF-7 cellular viability, suggesting a potential synergistic effect between the sigma receptors and the NO-mediated events. Overall, the combination of NO donor and sigma receptors ligands provided compounds with beneficial effects for the treatment of cancer.

  DOI：

  10.1021/acsmedchemlett.9b00661
• 作为产物：
  描述：

  4-苄基哌啶 、 3-溴丙腈 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以49%的产率得到3-(4-benzylpiperidin-1-yl)propanenitrile
  参考文献：
  名称：

  新型西格玛受体配体一氧化氮光电子供体：分子杂交的双重目标的抗增殖作用。

  摘要：

  这项贡献报告了新型混合化合物的合成和评估，这些化合物结合了sigma（σ）受体药效团和一氧化氮（NO）光供体。所有化合物保留其能力，以产生在可见光下NO，并具有整体σ受体纳摩尔亲和力，与它们中的一个（图8b显示出显着的σ）2受体的选择性。化合物8b的，图11A和11B分别对致瘤性的MCF-7和A2058细胞中测试表达高水平的σ 2和σ 1受体。在光激发下检测到细胞活力的显着损失，而在黑暗中检测到的影响可忽略不计。此外，它们在黑暗中或在非致瘤性NCTC-2544角质形成细胞上照射下均未显示任何明显的细胞毒性。通过细胞内NO检测和总亚硝酸盐估计证明了NO诱导的细胞活力降低。首次报道了σ受体部分和NO光供体的组合，提供了可用于癌症治疗的独特配体。

  DOI：

  10.1021/acs.jmedchem.7b00791

文献信息

• Dihydropyridines and new uses thereof
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US05767131A1

  公开（公告）日：1998-06-16

  The invention provides a method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound having the structure: ##STR1## wherein Y is --(CH.sub.2).sub.n --, where n is 1, 2, 3, 4 or 5; --(CH.sub.2).sub.h --O--(CH.sub.2).sub.k --, where h and k are independently the same or different and are 2, 3 or 4; --(CH.sub.2).sub.h --CH.dbd.CH--(CH.sub.2).sub.k --; or --(CH.sub.2).sub.h --C.tbd.C--(CH.sub.2).sub.k --, where h and k are independently the same or different and are 1, 2, 3 or 4; wherein Z is O, NH, or CH.sub.2 ; wherein R.sup.1 is a linear or branched chain alkyl, alkoxyalkyl or arylalkyl group; wherein R.sup.2 and R.sup.4 are independently the same or different and are H, or a linear or branched chain alkyl group; wherein R.sup.3 is H, a linear or branched chain alkyl, alkoxy, alkoxyalkyl or acyl group; and wherein R.sup.5 and R.sup.6 are independently the same or different and are H, OH, Cl, Br, F, NO.sub.2, CN, CF.sub.3, or NH.sub.2, or a linear or branched chain alkyl, alkoxy, alkoxycarbonyl, acyl, alkylsulfoxide, alkylsulfone, or mono- or dialkylamino group. Other active compounds containing one, two or three rings are also disclosed as well as pharmaceutical compositions prepared therefrom and methods of use in the treatment of BPH, inhibition of cholesterol synthesis, and reduction of intraocular pressure.

  该发明提供了一种治疗良性前列腺增生的方法，包括向受试者施用具有以下结构的化合物的治疗有效量： 其中Y为--(CH.sub.2).sub.n --，其中n为1、2、3、4或5；--(CH.sub.2).sub.h --O--(CH.sub.2).sub.k --，其中h和k独立且相同或不同，为2、3或4；--(CH.sub.2).sub.h --CH.dbd.CH--(CH.sub.2).sub.k --；或--(CH.sub.2).sub.h --C.tbd.C--(CH.sub.2).sub.k --，其中h和k独立且相同或不同，为1、2、3或4；其中Z为O、NH或CH.sub.2；其中R.sup.1为线性或支链烷基、烷氧基烷基或芳基烷基；其中R.sup.2和R.sup.4独立且相同或不同，为H，或线性或支链烷基；其中R.sup.3为H、线性或支链烷基、烷氧基、烷氧基烷基或酰基；其中R.sup.5和R.sup.6独立且相同或不同，为H、OH、Cl、Br、F、NO.sub.2、CN、CF.sub.3或NH.sub.2，或线性或支链烷基、烷氧基、烷氧羰基、酰基、烷基亚砜、烷基砜、或单烷基或二烷基氨基基团。还公开了含有一、两个或三个环的其他活性化合物，以及由此制备的药物组合物和在治疗BPH、抑制胆固醇合成和降低眼压中的使用方法。
• A Structure−Activity Relationship Study of Novel Phenylacetamides Which Are Sodium Channel Blockers
  作者：Ioannis Roufos、Sheryl Hays、Roy D. Schwarz

  DOI：10.1021/jm950467y

  日期：1996.1.1

  A structure-activity relationship study of a series of novel Na+ channel blockers, structurally related to N-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenylbenzeneacetamide (1, PD85639) is described. The diphenylacetic acid portion of the molecule was left unchanged throughout the study, while structural features in the amine portion and the amide alkyl linkage of the molecule were modified. The compounds were tested for inhibition of veratridine-stimulated Na+ influx in CHO cells expressing type IIA Na+ channels. Several derivatives show a trend toward more potent Na+ channel blockade activity with increasing lipophilicity of the amine portion of the molecule. The presence of a phenyl ring near the amine increases inhibitory potency. A three-carbon spacer between the amide and amine is optimal, and a secondary amide linkage is preferred.
• Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer’s disease
  作者：Poonam Meena、Vishal Nemaysh、Manisha Khatri、Apra Manral、Pratibha Mehta Luthra、Manisha Tiwari

  DOI：10.1016/j.bmc.2014.12.057

  日期：2015.3

  Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer's disease (AD). Following this approach, a new series of N'-(4-benzylpiperidin-/piperazin-/benzhydrylpiperazin-1-yl) alkylamine derivatives were designed, synthesized and biologically evaluated as inhibitors of cholinesterases (ChEs), amyloid-beta (A beta) self aggregation and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives strongly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values in the low-nanomolar range, and were clearly more potent than the reference compound donepezil in this regard. Among them, inhibitors 5h and 5k, strongly inhibited AChE, with IC50 value of 6.83 nM and 2.13 nM, respectively, and particularly, compound 5k was found to be highly selective for AChE (similar to 38-fold). Moreover, both kinetic analysis of AChE inhibition and the docking study suggested that 5k binds simultaneously to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit self-induced A beta(1-42) aggregation at 25 mu M with percentage inhibition from similar to 54% to 89% and specially compound 5k provided highest inhibition (88.81%). Also, the derivatives containing methoxy and hydroxy groups showed potent oxygen radical absorbance capacity (ORAC) ranging from 2.2- to 4.4-fold of the Trolox value. Furthermore, results of ADMET studies suggested that all compounds exhibited appropriate drug like properties. Taken together, these results suggest that 5k might be a promising lead compound for further AD drug development. (C) 2014 Elsevier Ltd. All rights reserved.
• US5767131A
  申请人：——

  公开号：US5767131A

  公开（公告）日：1998-06-16
• US6211198B1
  申请人：——

  公开号：US6211198B1

  公开（公告）日：2001-04-03