2-(6-phenylhexyl)isoindoline-1,3-dione | 138619-78-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(6-phenylhexyl)isoindoline-1,3-dione
• 英文别名: 2-(6-phenylhexyl)-1,3-dihydro-1,3-dioxo-2H-isoindole；N-(6-phenylhexyl)phthalimide；2-(6-phenylhexyl)isoindole-1,3-dione
• CAS: 138619-78-0
• 化学式: C₂₀H₂₁NO₂
• 分子量: 307.392
• InChiKey: IUCDQKXQBPVYLU-UHFFFAOYSA-N

物化性质

• 沸点：
  462.4±24.0 °C(Predicted)
• 密度：
  1.151±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(6-phenylhexyl)isoindoline-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 6-苯基-1-己胺
  参考文献：
  名称：

  由单一阴离子配体实现的苄胺，苯乙胺和苯丙胺衍生的酰胺的亚选择性CH硼化

  摘要：

  巧妙的定位：结合有远端阴离子磺酸盐基团的联吡啶配体可将铱催化的硼化反应引导至一系列含酰胺芳烃的间位。提出该选择性是氢键相互作用的结果，该氢键相互作用将铱金属中心正确定位在关键的CH活化中。

  DOI：

  10.1002/anie.201708967
• 作为产物：
  描述：

  苯已酸 在 lithium aluminium tetrahydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 20.0h， 生成 2-(6-phenylhexyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure–Activity Relationship (SAR) Studies

  摘要：

  Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads.

  DOI：

  10.1021/acs.jmedchem.5b01188

文献信息

• Nickel/Cobalt-Catalyzed C(sp³)–C(sp³) Cross-Coupling of Alkyl Halides with Alkyl Tosylates
  作者：Kimihiro Komeyama、Takuya Michiyuki、Itaru Osaka

  DOI：10.1021/acscatal.9b03352

  日期：2019.10.4

  The C(sp3)–C(sp3) cross-coupling of alkyl halides with alkyl tosylates has been developed by employing a combination of nickel and nucleophilic cobalt catalysts in the presence of a manganese reductant. This method provides a straightforward route to a diverse set of not only secondary–primary but also primary–primary C(sp3)–C(sp3) linkages under mild conditions without using alkyl-metallic reagents

  烷基卤化物与甲苯磺酸烷基酯的C（sp 3）–C（sp 3）交叉偶联是通过在锰还原剂存在下使用镍和亲核钴催化剂的组合来开发的。这种方法为在温和条件下不使用烷基金属试剂的情况下，不仅可以实现二级（一级）连接，而且还可以一级至一级（一级）C（sp 3）-C（sp 3）连接提供了直接的途径。机理研究表明，烷基卤化物和烷基甲苯磺酸盐均可形成烷基。另外，交叉偶联可用于组蛋白脱乙酰基酶抑制剂Vorinostat的短期合成。
• Fatty Acid Amide Hydrolase (FAAH), Acetylcholinesterase (AChE), and Butyrylcholinesterase (BuChE): Networked Targets for the Development of Carbamates as Potential Anti-Alzheimer’s Disease Agents
  作者：Serena Montanari、Laura Scalvini、Manuela Bartolini、Federica Belluti、Silvia Gobbi、Vincenza Andrisano、Alessia Ligresti、Vincenzo Di Marzo、Silvia Rivara、Marco Mor、Alessandra Bisi、Angela Rampa

  DOI：10.1021/acs.jmedchem.6b00609

  日期：2016.7.14

  a viable avenue for the treatment of neurodegeneration, being involved in neuroprotective and anti-inflammatory processes. In particular, indirectly enhancing endocannabinoid signaling to therapeutic levels through FAAH inhibition might be beneficial for neurodegenerative disorders such as Alzheimer’s disease, effectively preventing or slowing the progression of the disease. Hence, in the search for

  内源性大麻素系统的调节正在成为治疗神经退行性疾病的可行途径，参与神经保护和抗炎过程。特别地，通过FAAH抑制间接增强内源性大麻素信号传导至治疗水平可能有益于神经退行性疾病，例如阿尔茨海默氏病，有效预防或减慢疾病的发展。因此，在寻找更有效的阿尔茨海默氏病治疗方法中，本文将多目标导向的配体范式用于氨基甲酸酯的设计，该氨基甲酸酯能够同时靶向最近提出的内源性大麻素系统和经典的胆碱酯酶系统，并实现有效的双重治疗。 FAAH /胆碱酯酶抑制剂。在这两个合成的化合物系列中，9和19被确定为有效的双重FAAH / ChE抑制剂，具有均衡的纳摩尔活性。因此，9和19可被视为阿尔茨海默氏病治疗的新有希望的候选者。
• Monocyclic pteridine analogs. Inhibition of Escherichia coli dihydropteroate synthase by 6-amino-5-nitrosoisocytosines
  作者：O. William Lever、Lawrence N. Bell、H. Michael McGuire、Robert Ferone

  DOI：10.1021/jm00150a019

  日期：1985.12

  inhibitors of dihydropteroate synthase from Escherichia coli. A number of 6-(alkylamino)-5-nitrosoisocytosines have in vitro potency equivalent with or superior to that of therapeutically effective sulfonamide inhibitors of the synthase. The sulfonamide drugs are known to compete for the p-aminobenzoic acid binding site of the synthase, and kinetic analysis of inhibition of the synthase by 6-(methyl

  在体外评价了多种5，6-二取代的异胞嘧啶衍生物作为来自大肠杆菌的二氢蝶呤合酶的抑制剂。许多6-（烷基氨基）-5-亚硝基异胞嘧啶在体外具有与合成酶的治疗有效磺酰胺抑制剂相当或更高的体外效力。已知磺酰胺类药物会竞争合酶的对氨基苯甲酸结合位点，并通过6-（甲基氨基）-5-亚硝基异胞嘧啶（16; I50 = 1.6 microM）和6- （3-苯氧丙基）氨基类似物（33; I50 = 3.7 microM）表明亚硝基异胞嘧啶抑制剂与蝶啶底物竞争该酶。结构活性研究表明，酶表面对异胞嘧啶6-氨基功能周围区域的空间体积具有较低的耐受性。然而，这种空间不耐受性可以通过具有6-（ω-苯基烷基）氨基取代基的某些类似物实现的正构构相互作用而在很大程度上抵消。例如，6-[（（7-苯基庚基）氨基] -5-亚硝基异胞嘧啶（28）与6-甲基氨基化合物16一样有效（I50 = 1.4 microM）抑制剂。尽管5-亚硝基
• Substituted-4-thiazolidinone derivatives
  申请人：A. H. Robins Company, Inc.

  公开号：US05061720A1

  公开（公告）日：1991-10-29

  Disclosed are novel substituted 4-thiazolidinone derivatives having cyclooxygenase and 5-lipoxygenase inhibiting properties and which are topical antiinflammatory agents for inflammed conditions of the skin having the formula: ##STR1## wherein R is hydrogen or loweralkyl; R.sup.1 is loweralkyl or aryl; X is --(CH.sub.2)-aryl, --O--(CH.sub.2).sub.0-3 -aryl, --C(O)(CH.sub.2).sub.0-3 -aryl, --CH(OH)--(CH.sub.2).sub.0-3 -aryl or 3,4 ##STR2## (to form naphthyl ring); aryl is phenyl, substituted phenyl, or 2,3 or 4 pyridyl; W is oxygen; Q is -(alk.sup.1).sub.0-1 --(O).sub.0-1 --(B).sub.0-1 --(alk.sup.2).sub.0-1 --[C(O)Z].sub.0-1 ; B is ##STR3## Z is OR.sup.3 or NR.sup.4 R.sup.5 where R.sup.3 is hydrogen, loweralkyl, or a pharmaceutically acceptable metal cation, R.sup.4 and R.sup.5 are hydrogen or loweralkyl; alk.sup.1 and alk.sup.2 are lower alkylene or loweralkyleneloweralkyl, Y is hydrogen, loweralkyl, loweralkoxy, trifluoromethyl, nitro, or halo; and the stereoisomers and optical isomers thereof and pharmaceutically acceptable acid addition salts which form when a basic nitrogen is present.

  本发明涉及一种新的取代4-噻唑烷酮衍生物，具有环氧化酶和5-脂氧合酶抑制作用，并且是用于皮肤炎症条件的局部抗炎药物，其化学结构如下：其中R为氢或较低烷基；R.sup.1为较低烷基或芳基；X为--(CH.sub.2)-芳基，--O--(CH.sub.2).sub.0-3 -芳基，--C(O)(CH.sub.2).sub.0-3 -芳基，--CH(OH)--(CH.sub.2).sub.0-3 -芳基或3,4-二氢萘基；芳基为苯基，取代苯基，或2,3或4-吡啶基；W为氧；Q为-(烷基.sup.1).sub.0-1 --(O).sub.0-1 --(B).sub.0-1 --(烷基.sup.2).sub.0-1 --[C(O)Z].sub.0-1；B为Z为OR.sup.3或NR.sup.4 R.sup.5，其中R.sup.3为氢、较低烷基或药用可接受金属阳离子，R.sup.4和R.sup.5为氢或较低烷基；烷基.sup.1和烷基.sup.2为较低烷基或较低烷基较低烷基，Y为氢、较低烷基、较低烷氧基、三氟甲基、硝基或卤素；以及其立体异构体、光学异构体和在存在碱性氮时形成的药用可接受酸盐。
• [EN] SUBSTITUTED BENZOXAZOLONE DERIVATIVES AS ACID CERAMIDASE INHIBITORS, AND THEIR USE AS MEDICAMENTS<br/>[FR] DÉRIVÉS DE BENZOXAZOLONE SUBSTITUÉS COMME INHIBITEURS DE LA CÉRAMIDASE ACIDE, ET LEUR UTILISATION COMME MÉDICAMENTS
  申请人：FOND ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：WO2015173169A1

  公开（公告）日：2015-11-19

  The present invention relates to substituted benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides substituted benzoxazolone derivatives for use in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.

  本发明涉及取代苯并噁唑酮衍生物作为酸酰胺酶抑制剂，含有这些抑制剂的药物组合物以及用于治疗调节酰胺水平在临床上相关的疾病的方法。该发明还提供了用于治疗癌症、炎症、疼痛、炎症性疼痛或肺部疾病的取代苯并噁唑酮衍生物。