4-(4-甲氧苄基)环己酮 | 67807-29-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 4-(4-甲氧苄基)环己酮
• 英文名称: 4-(4-methoxybenzyl)cyclohexanone
• 英文别名: 4-(4-methoxybenzyl)-cyclohexanone；4-[(4-Methoxyphenyl)methyl]cyclohexan-1-one
• CAS: 67807-29-8
• 化学式: C₁₄H₁₈O₂
• 分子量: 218.296
• InChiKey: VUYADWDOAFPYIR-UHFFFAOYSA-N

物化性质

• 沸点：
  345.4±15.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-甲氧苄基)环己酮 在 4-二甲氨基吡啶 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 、 lithium diisopropyl amide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  使用支架跳跃方法发现具有镇痛活性的口服生物利用度的基于环己醇的NR2B选择性NMDA受体拮抗剂

  摘要：

  NR2B亚基含有Ñ甲基d天冬氨酸（NMDA）受体是用于慢性疼痛有吸引力的靶点，因为它在疾病状态的参与和在中枢神经系统中其有限的分布。利用脚手架跳跃方法，基于环己醇的铅6a和6c被鉴定为有效的NR2B选择性NMDA拮抗剂。通过用异恶唑替代先导中的酰胺进一步优化该系列药物，以及努力优化药代动力学特性，导致发现了口服可用的脑渗透剂7k和7l，这在小鼠福尔马林试验的早期和晚期均显示出镇痛作用。 。

  DOI：

  10.1016/j.bmcl.2017.06.076
• 作为产物：
  描述：

  (4-羟基苯基)-(4-甲氧基苯基)甲酮 在 氢氧化钾 、 一水合肼 作用下， 以 二乙二醇 为溶剂， 反应 2.0h， 生成 4-(4-甲氧苄基)环己酮
  参考文献：
  名称：

  某些苯并吗啡酮类似物的合成及其止痛活性。

  摘要：

  苯并吗啡类似物8-hydroxy-3-methyl-2,3,4,5-tetrahydro-1,4-methano-1H-3-benzazepine（1），8-hydroxy-2-methyl-2,3,4 ，5-四氢-1,4-甲基-1H-2-苯并ze庚因（2），9-羟基-2-甲基-1,2,3,4,5,6-六氢-1,5，-甲基2合成了-benzazocine（3）和10-羟基-2-甲基-2,3,4,5,6,7-六氢-1,6-甲基-1H-2-benzazonine（4）评估其镇痛作用。在任何这些化合物中仅发现轻微的止痛活性。讨论了氮到芳香环距离对于止痛药-受体相互作用的重要性。

  DOI：

  10.1021/jm00209a003

文献信息

• Nitrogen heterocycles
  申请人：John Wyeth & Brother

  公开号：US05681839A1

  公开（公告）日：1997-10-28

  This invention concerns a compound of generic formula ##STR1## or a pharmaceutically acceptable salt thereof, where the dotted lines represent optional bonds, R.sup.3 is an optionally substituted C.sub.6 -C.sub.10 aryl or heteroaryl group; R.sup.4 represents hydrogen, or a group of formula --CR.sup.a R.sup.b R.sup.c where R.sup.a, R.sup.b and R.sup.c are independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl C.sub.6 -C.sub.10 aryl, heteroaryl, C.sub.1 -C.sub.6 alkyl substituted by optionally substituted C.sub.6 -C.sub.10 aryl or heteroaryl; R' represents one or more optional substituents the same or different, selected from halogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.7 alkoxycarbonyl, C.sub.1 -C.sub.6 hydroxyalkyl, CN, aminocarbonyl, C.sub.2 -C.sub.7 alkanoyloxy(C.sub.1 -C.sub.6)alkyl, carboxy, C.sub.2 -C.sub.7 alkanoxylamino, C.sub.6 -C.sub.10 or heteroaryl or an (C.sub.6 -C.sub.10 aryl)alkyl or a heteroaryl alkyl radical; R" represents one or more optional mono- or di- valent substituents in the 5, 7 or 8 positions selected from C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.7 alkanoyloxy, hydroxy, amino, C.sub.2 -C.sub.7 alkanoylamino, C.sub.1 -C.sub.6 alkylamino, C.sub.1 -C.sub.6 hydroxyalkyl, and R" can also represent hydroxy in the 6 position when the optional bond is absent; oxo and methylene; which compounds have pharmaceutical uses conferred by their ability to block voltage gated potassium channels.

  这项发明涉及一种通用结构式##STR1##的化合物或其药学上可接受的盐，其中虚线代表可选键，R.sup.3是一个可选择取代的C.sub.6 -C.sub.10芳基或杂环芳基；R.sup.4代表氢，或者一个式--CR.sup.a R.sup.b R.sup.c的基团，其中R.sup.a、R.sup.b和R.sup.c分别独立地选自氢、C.sub.1 -C.sub.6烷基、C.sub.6 -C.sub.10芳基、杂环芳基、C.sub.1 -C.sub.6烷基取代的可选择取代的C.sub.6 -C.sub.10芳基或杂环芳基；R'代表一个或多个可选取代基，相同或不同，选自卤素、C.sub.1 -C.sub.6烷基、C.sub.2 -C.sub.7烷氧羰基、C.sub.1 -C.sub.6羟基烷基、CN、氨基羰基、C.sub.2 -C.sub.7烷酰氧基(C.sub.1 -C.sub.6)烷基、羧基、C.sub.2 -C.sub.7烷氧基氨基、C.sub.6 -C.sub.10或杂环芳基或一个(C.sub.6 -C.sub.10芳基)烷基或一个杂环芳基烷基基团；R"代表在5、7或8位置选自C.sub.1 -C.sub.6烷基、C.sub.2 -C.sub.7烷酰氧基、羟基、氨基、C.sub.2 -C.sub.7烷酰氨基、C.sub.1 -C.sub.6烷基氨基、C.sub.1 -C.sub.6羟基烷基的一个或多个可选的单价或二价取代基，当可选键不存在时，R"还可以代表6位置的羟基；氧代和亚甲基；这些化合物通过其阻断电压门控钾通道的能力具有药用价值。
• Synthesis and Antiparasitic and Antitumor Activity of 2,4-Diamino-6-(arylmethyl)-5,6,7,8-tetrahydroquinazoline Analogues of Piritrexim
  作者：Andre Rosowsky、Andrew T. Papoulis、Ronald A. Forsch、Sherry F. Queener

  DOI：10.1021/jm980572i

  日期：1999.3.1

  followed by hydrogenation (H2/Pd-C) and acidolysis, yielded the corresponding 4-(arylmethyl)cyclohexanones, which were then condensed with cyanoguanidine to form the tetrahydroquinazolines. Three simple 2, 4-diamino-6-alkyl-5,6,7,8-tetrahydroquinazoline model compounds (9a-c) were also prepared in one step from commercially available 4-alkylcyclohexanones by this method. Enzyme inhibition assays against

  合成了19种先前未描述的2,4-二氨基-6-（芳基甲基）-5,6,7，8-四氢喹唑啉（5a-m，10-12）作为更大努力的一部分，以评估亲脂性二氢叶酸还原酶的治疗潜力（DHFR）抑制剂，可防止艾滋病的机会性感染。将适当取代的（芳基甲基）三苯基膦与4,4-亚乙基二氧环己酮缩合，然后加氢（H2 / Pd-C）和酸解反应，得到相应的4-（芳基甲基）环己酮，然后将其与氰基胍缩合形成四氢喹唑啉。还通过一步法从市售的4-烷基环己酮一步制备了三种简单的2，4-二氨基-6-烷基-5,6,7,8-四氢喹唑啉模型化合物（9a-c）。针对大鼠肝脏DHFR，卡氏肺孢子虫DHFR，进行了弓形虫双功能DHFR-TS酶的比较，比较了IC50（rat）/ IC50（P。carinii）和IC50（rat）/ IC50（T。gondii）的选择性比。Carinii DHFR的三种最有效抑制剂是2,5-二甲氧基苄基（5j），3，4-二甲氧基苄基（5k）和3
• Dicyclic and Tricyclic Diaminopyrimidine Derivatives as Potent Inhibitors of <i>Cryptosporidium parvum</i> Dihydrofolate Reductase: Structure-Activity and Structure-Selectivity Correlations
  作者：Richard G. Nelson、Andre Rosowsky

  DOI：10.1128/aac.45.12.3293-3303.2001

  日期：2001.12

  A structurally diverse library of 93 lipophilic di- and tricyclic diaminopyrimidine derivatives was tested for the ability to inhibit recombinant dihydrofolate reductase (DHFR) cloned from human and bovine isolates of Cryptosporidium parvum (J. R. Vásquez et al., Mol. Biochem. Parasitol. 79:153–165, 1996). In parallel, the library was also tested against human DHFR and, for comparison, the enzyme from Escherichia coli . Fifty percent inhibitory concentrations (IC ₅₀ s) were determined by means of a standard spectrophotometric assay of DHFR activity with dihydrofolate and NADPH as the cosubstrates. Of the compounds tested, 25 had IC ₅₀ s in the 1 to 10 μM range against one or both C. parvum enzymes and thus were not substantially different from trimethoprim (IC ₅₀ s, ca. 4 μM). Another 25 compounds had IC ₅₀ s of <1.0 μM, and 9 of these had IC ₅₀ s of <0.1 μM and thus were at least 40 times more potent than trimethoprim. The remaining 42 compounds were weak inhibitors (IC ₅₀ s, >10 μM) and thus were not considered to be of interest as drugs useful against this organism. A good correlation was generally obtained between the results of the spectrophotometric enzyme inhibition assays and those obtained recently in a yeast complementation assay (V. H. Brophy et al., Antimicrob. Agents Chemother. 44:1019–1028, 2000; H. Lau et al., Antimicrob. Agents Chemother. 45:187–195, 2001). Although many of the compounds in the library were more potent than trimethoprim, none had the degree of selectivity of trimethoprim for C. parvum versus human DHFR. Collectively, the results of these assays comprise the largest available database of lipophilic antifolates as potential anticryptosporidial agents. The compounds in the library were also tested as inhibitors of the proliferation of intracellular C. parvum oocysts in canine kidney epithelial cells cultured in folate-free medium containing thymidine (10 μM) and hypoxanthine (100 μM). After 72 h of drug exposure, the number of parasites inside the cells was quantitated by indirect immunofluorescence microscopy. Sixteen compounds had IC ₅₀ s of <3 μM, and five of these had IC ₅₀ s of <0.3 μM and thus were comparable in potency to trimetrexate. The finding that submicromolar concentrations of several of the compounds in the library could inhibit in vitro growth of C. parvum in host cells in the presence of thymidine (dThd) and hypoxanthine (Hx) suggests that lipophilic DHFR inhibitors, in combination with leucovorin, may find use in the treatment of intractable C. parvum infections.

  摘要 对 93 种亲脂性二环和三环二氨基嘧啶衍生物的结构多样性文库进行了测试，以检测其抑制从人和牛分离的副隐孢子虫中克隆的重组二氢叶酸还原酶（DHFR）的能力。 副猪隐孢子虫 (J. R. Vásquez et al., Mol. Biochem. Parasitol. 79:153-165, 1996)。与此同时，该文库还针对人类 DHFR 进行了测试，并与来自 大肠杆菌 .五成抑制浓度（IC 50 s）是通过以二氢叶酸和 NADPH 为共底物的 DHFR 活性标准分光光度法测定的。在测试的化合物中，25 个化合物的 IC 50 在 1 至 10 μM 范围内，对一种或两种 C. parvum 因此与三甲氧苄啶（IC 50 s，约为 4 μM）没有本质区别。另外 25 种化合物的 IC 50 s 为 1.0 μM，其中 9 种化合物的 IC 50 为 0.1 μM，因此药效至少是三甲氧苄啶的 40 倍。其余 42 种化合物为弱抑制剂（IC 50 s，>10 μM），因此不被认为是对这种生物有用的药物。分光光度法酶抑制测定的结果与最近在酵母互补测定中获得的结果之间通常具有良好的相关性（V. H. Brophy 等人，Antimicrob.Agents Chemother.44:1019-1028, 2000; H. Lau et al.Agents Chemother.45:187-195, 2001).虽然文库中的许多化合物都比三甲氧苄氨嘧啶更有效，但没有一种化合物具有三甲氧苄氨嘧啶对副猪嗜血杆菌的选择性。 副猪嗜血杆菌 对人类 DHFR 的选择性。总之，这些检测结果构成了目前最大的亲脂性抗酚化合物潜在抗隐孢子虫药物数据库。该化合物库中的化合物还作为细胞内副猪嗜血杆菌增殖抑制剂进行了测试。 副猪嗜血杆菌 卵囊在含有胸苷（10 μM）和次黄嘌呤（100 μM）的无叶酸培养基中培养的犬肾上皮细胞中的增殖抑制剂。药物暴露 72 小时后，通过间接免疫荧光显微镜对细胞内的寄生虫数量进行量化。16种化合物的IC 50 为 <3 μM，其中五个化合物的 IC 50 s 为 <0.3 μM，因此其效力与三甲曲沙相当。研究发现，库中几种亚摩尔浓度的化合物可抑制副嗜血杆菌的体外生长。 副猪嗜血杆菌 在胸苷（dThd）和次黄嘌呤（Hx）存在的宿主细胞中的体外生长。 C. parvum 感染。
• US5681839A
  申请人：——

  公开号：US5681839A

  公开（公告）日：1997-10-28
• US5753676A
  申请人：——

  公开号：US5753676A

  公开（公告）日：1998-05-19