2-羟基-6-苯基己腈 | 288863-28-5

• 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: 2-羟基-6-苯基己腈
• 英文名称: 2-hydroxy-6-phenylhexanenitrile
• CAS: 288863-28-5
• 化学式: C₁₂H₁₅NO
• 分子量: 189.257
• InChiKey: DYLWAQBBAIIOSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-羟基-6-苯基己腈 在 2,6-二甲基吡啶 、 bis(triphenylphosphine)nickel(II) chloride 、 4,4'-二叔丁基-2,2'-二吡啶 、 锌 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 23.0h， 生成 2-(dimethyl(vinyl)silyl)-6-phenylhexanenitrile
  参考文献：
  名称：

  镍催化 α-氰基烷基亲电子试剂和氯硅烷的还原 C(sp3)−Si 交叉偶联

  摘要：

  报道了由 α-氰基和氯硅烷活化的烷基亲电试剂在镍/锌催化下的交叉亲电偶联。元素锌是该还原偶联过程中的化学计量还原剂。由此，可以从两种亲电反应物开始形成C(sp 3 )-Si键，而之前的方法依赖于碳亲核试剂和硅亲电试剂的组合，反之亦然。

  DOI：

  10.1002/anie.202107492
• 作为产物：
  描述：

  苯戊醇 在 sodium hypochlorite 、 4-乙酰氨-2,2,6,6-四甲基哌啶-1-氧 、 碳酸氢钠 、 sodium hydrogensulfite 、 sodium bromide 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 19.75h， 生成 2-羟基-6-苯基己腈
  参考文献：
  名称：

  在分子对接计算和分子动力学模拟的指导下，开发了一种有效的分泌型磷脂酶A2的2-氧酰胺抑制剂。

  摘要：

  抑制IIA组分泌的磷脂酶A2（GIIA sPLA2）已成为药物化学家的重要目标。先前我们已经表明，结合了2-氧酰胺功能的抑制剂可能会抑制人和小鼠GIIA sPLA2。在此，描述了使用已知的抑制剂7的结构通过分子对接计算来开发新的有效抑制剂的方法。新化合物的合成和生物学评估表明，基于（S）-缬氨酸GK241的长链2-氧代酰胺可提高活性（分别针对人和小鼠GIIA sPLA2的IC50 = 143nM和68nM）。此外，采用分子动力学模拟来阐明GK241的有效和选择性抑制活性。

  DOI：

  10.1016/j.bmc.2016.02.040

文献信息

• Comprehensive Analysis of Structure–Activity Relationships of α-Ketoheterocycles as <i>sn</i>-1-Diacylglycerol Lipase α Inhibitors
  作者：Freek J. Janssen、Marc P. Baggelaar、Jessica J. A. Hummel、Herman S. Overkleeft、Benjamin F. Cravatt、Dale L. Boger、Mario van der Stelt

  DOI：10.1021/acs.jmedchem.5b01627

  日期：2015.12.24

  Diacylglycerol lipase alpha (DAGL alpha) is responsible for the formation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the central nervous system. DAGL alpha inhibitors are required to study the physiological mile of 2-AG. Previously, we identified the alpha-ketoheterocycles as potent and highly selective DAGL alpha inhibitors. Here, we present the first comprehensive structure activity relationship study Of alpha-ketohetero cycles as DAGL alpha inhibitors. Our findings indicate that the active site, of DAGL alpha is remarkably sensitive to the type of heterocyclic scaffold with oxazolo-4N-pridines as the most active framework We uncovered a fundamental substituent effect in which electron-withdrawing meta-oxazole substituents increased inhibitor potency. (C-6-C-9)-iacyl chains with a distal phenyl group proved to be the most potent inhibitors. The integrated SAR data was consistent with the proposed binding pose in a DAGL alpha homology model. Altogether, our results may guide the design of future DAGL alpha inhibitors as leads for molecular therapies to treat neuroinflammation, obesity, and related metabolic disorders.
• PHARMACEUTICALLY ACTIVE COMPOUNDS AS DAG-LIPASE INHIBITORS
  申请人：Universiteit Leiden

  公开号：EP3145935A1

  公开（公告）日：2017-03-29
• COMPOUND
  申请人：Kokotos George

  公开号：US20110136879A1

  公开（公告）日：2011-06-09

  The invention provides compounds of formula (I) wherein X is O or S; R 1 is H, OH, SH, nitro, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , halo, haloC 1-6 alkyl, CN, C 1-6 -alkyl, OC 1-6 alkyl, C 1-6 alkylCOOH, C 1-6 alkylCOOC 1-6 alkyl, C 2-6 -alkenyl, C 3-10 cycloalkyl, C 6-10 aryl, C 1-6 alkylC 6-10 aryl, heterocyclyl, heteroaryl, CONH 2 , CONHC 1-6 alkyl, CON(C 1-6 alkyl) 2 , OCOC 1-6 alkyl, or is an acidic group, such as a group comprising a carboxyl, phosphate, phosphinate, sulfate, sulfonate, or tetrazolyl group; R 2 is as defined for R 1 or R 1 and R 2 taken together can form a 6-membered aromatic ring optionally substituted by up to 4 groups R 5 ; R 3 is H, halo (preferably fluoro), or CHal 3 (preferably CF 3 ), each R 5 is defined as for R 1 ; V 1 is a covalent bond or a C 1-20 alkyl group, or C 2-20 -mono or multiply unsaturated alkenyl group; said alkyl or alkenyl groups being optionally interupted by one or more heteroatoms selected from O, NH, N(C 1-6 alkyl), S, SO, or SO 2 ; M 1 is absent or is a C 5-10 cyclic group or a C 5-15 aromatic group; and R 4 is H, halo, OH, CN, nitro, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , haloC 1-6 alkyl, a C 1-20 alkyl group, or C 2-20 -mono or multiply unsaturated alkenyl group, said C 1-20 alkyl or C 2-20 alkenyl groups being optionally interupted by one or more heteroatoms selected from O, NH, N(C 1-6 alkyl), S, SO, or SO 2 ; with the proviso that the group V 1 M 1 R 4 as a whole provides at least 4 backbone atoms from the C(R 3 ) group; or a salt, ester, solvate, N-oxide, or prodrug thereof; for use in the treatment of a chronic inflammatory condition.
• [EN] PHARMACEUTICALLY ACTIVE COMPOUNDS AS DAG-LIPASE INHIBITORS<br/>[FR] COMPOSÉS PHARMACEUTIQUEMENT ACTIFS À TITRE D'INHIBITEURS DE LIPASES DAG
  申请人：UNIV LEIDEN

  公开号：WO2016188972A1

  公开（公告）日：2016-12-01

  The present invention relates to novel compounds which are selective inhibitors of diacylglycerol lipase alpha and beta. These compounds are suitable for the treatment or prevention of disorders associated with, accompanied by or caused by increased 2-arachidonoylglycerol levels. Diacylglycerol lipase-a (alternative name: Snl-specific diacylglycerol hydrolase a; DAGL-a) and -β are enzymes responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. Selective and reversible inhibitors are required to study the function of DAGLs in neuronal cells in an acute and temporal fashion. The inventive compounds are in particular suitable for the treatment of neurodegenerative diseases, inflammatory diseases, drug abuse and impaired energy balance, such as obesity, wherein X1 is -CH-, -CF- or -N-.