methyl 4-phenylbutanimidate hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-phenylbutanimidate hydrochloride
• 英文别名: Hydron;methyl 4-phenylbutanimidate;chloride
• 化学式: C₁₁H₁₅NO*ClH
• 分子量: 213.707
• InChiKey: OKCYMSQFRXSBMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  33.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 4-phenylbutanimidate hydrochloride 在 碘苯二乙酸 、 二异丁基氢化铝 、 碳酸氢钠 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醚 、 甲苯 、 乙腈 为溶剂， 反应 17.0h， 生成 5-苯基-2-吡咯烷酮
  参考文献：
  名称：

  可见光介导的远程γ-C（sp 3）–H烷基酰亚胺的官能化：4-碘-3,4-二氢吡咯衍生物的合成

  摘要：

  报道了一种对功能化的二氢吡咯衍生物的有效且环境友好的合成方法。通过从原位生成的亚氨酸根N-自由基通过1,5-氢原子转移，烷基亚氨酸盐的化学选择性分子内N-C键形成进行了开发。这种设计策略的主要优点在于原料的选择，温和的反应条件，高的化学和非对映选择性，清洁的能源以及良好的官能团耐受性。此外，4-碘二氢吡咯可以容易地转化成多种有用的衍生物。

  DOI：

  10.1021/acs.orglett.8b02022
• 作为产物：
  描述：

  甲醇 、 4-苯基丁腈 在 乙酰氯 作用下， 反应 12.0h， 以91%的产率得到methyl 4-phenylbutanimidate hydrochloride
  参考文献：
  名称：

  可见光介导的远程γ-C（sp 3）–H烷基酰亚胺的官能化：4-碘-3,4-二氢吡咯衍生物的合成

  摘要：

  报道了一种对功能化的二氢吡咯衍生物的有效且环境友好的合成方法。通过从原位生成的亚氨酸根N-自由基通过1,5-氢原子转移，烷基亚氨酸盐的化学选择性分子内N-C键形成进行了开发。这种设计策略的主要优点在于原料的选择，温和的反应条件，高的化学和非对映选择性，清洁的能源以及良好的官能团耐受性。此外，4-碘二氢吡咯可以容易地转化成多种有用的衍生物。

  DOI：

  10.1021/acs.orglett.8b02022

文献信息

• d-Amino acid oxidase inhibitors based on the 5-hydroxy-1,2,4-triazin-6(1H)-one scaffold
  作者：Niyada Hin、Bridget Duvall、James F. Berry、Dana V. Ferraris、Rana Rais、Jesse Alt、Camilo Rojas、Barbara S. Slusher、Takashi Tsukamoto

  DOI：10.1016/j.bmcl.2016.02.068

  日期：2016.4

  4-triazin-6(1H)-one derivatives were designed and synthesized as a new class of d-amino acid oxidase (DAAO) inhibitors. Some of the newly synthesized derivatives showed potent inhibitory activity against human DAAO with IC50 values in the nanomolar range. Among them, 6-hydroxy-3-phenethyl-1,2,4-triazin-5(2H)-one 6b and 3-((6-fluoronaphthalen-2-yl)methylthio)-6-hydroxy-1,2,4-triazin-5(2H)-one 6m were found

  设计并合成了一系列3-取代的5-羟基-1,2,4-三嗪-6（1H）-one衍生物，作为一类新型的d-氨基酸氧化酶（DAAO）抑制剂。一些新合成的衍生物显示出对人DAAO的有效抑制活性，IC50值在纳摩尔范围内。其中6-羟基-3-苯乙基-1,2,4-三嗪-5（2H）-一6b和3-（（6-氟萘-2-基）甲硫基）-6-羟基-1,2，发现4-triazin-5（2H）-1 6m在小鼠肝微粒体中代谢稳定。另外，与单独口服d-丝氨酸相比，发现化合物6b可在小鼠中口服获得并且在与d-丝氨酸共同给药后能够增强血浆d-丝氨酸水平。
• Unusual reactivity of 4-carboxyamido-2-oxazoline systems: new synthesis of optically active n-sulphonyl derivatives.
  作者：S. Cossu、G. Giacomelli、S. Conti、M. Falorni

  DOI：10.1016/s0040-4020(01)90418-1

  日期：1994.4

  enantiomeric pure α-amino-β-hydroxy acids, react with aryl- and alkyl sulphonyl chlorides in pyridine affording the corresponding optically active 2-alkyl-2-oxazoline-4-carboxyamido-N-sulphonyl derivatives without appreciable racemization.

  衍生自对映体纯α-氨基-β-羟基酸的旋光的2-烷基-2-恶唑啉-4-羧酰胺与吡啶中的芳基和烷基磺酰氯反应，得到相应的旋光的2-烷基-2-恶唑啉- 4-羧酰胺基-N-磺酰基衍生物，没有明显的外消旋作用。
• 2-Substituted histamines with G-protein-stimulatory activity
  作者：H Detert、A Hagelüken、R Seifert、W Schunack

  DOI：10.1016/0223-5234(96)88235-3

  日期：1995.1

  The cationic-amphiphilic 2-substituted histamines, 2-(3-chlorophenyl)histamine (2-[2-(3-chlorophenyl)-1H-imidazol-4-yl]ethanamine) and 2-(2-cyclohexylethyl)histamine, activate pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) of the G(i)-subfamily by a receptor-independent mechanism. We studied structure-activity relationships of 2-substituted histamine derivatives for this G-protein activation using six known and 12 newly synthesized compounds. Elongation of the alkyl chain between imidazole and the ring system enhanced the potency and efficiency of substances in activating high-affinity GTP hydrolysis, ie the enzymatic activity of G-protein alpha-subunits, in membranes of HL-60 leukemic cells. Cyclopentyl-, cyclohexyl- and norbornyl-substituted histamines were more effective and potent than phenyl-substituted histamines in mediating G-protein activation in HL-60 membranes and in activating reconstituted bovine brain G(i)/G(o)-proteins. Our data show that the chain length and the type of ring system are important determinants for receptor-independent G-protein activation by 2-substituted histamines. With respect to histamine H-1-receptors, most of the substances studied displayed weak antagonistic activity.
• 2-Alkyl-substituted histamines and hydroxyethylimidazoles with G-protein-stimulatory activity
  作者：H Detert、C Leschke、W Tögel、R Seifert、W Schunacki

  DOI：10.1016/0223-5234(96)89166-5

  日期：1996.1

  Cationic-amphiphilic 2-substituted histamines activate pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) by a receptor-independent mechanism. From our recent studies it became apparent that lipophilicity is an important determinant for this G-protein activation, but the influence of basicity remained unknown. We prepared seven novel 2-alkyl-substituted histamines and five novel 2-alkyl-substituted hydroxyethylimidazoles and studied their effects on high-affinity guanosine triphosphate (GTP) hydrolysis in membranes of the human leukemia cell line, HL-60. 2-Octylhistamine was found to be the most effective GTPase activator among 2-substituted histamines presently available (150% stimulation above basal), and 2-tetradecylhistamine is the most potent substance in this regard (pEC(50) = 5.9). Branching of the alkyl chain and the introduction of an ether group adversely affected GTPase activation. Compared to a phenyl ring, a bulky adamantyl sphere enhanced G-protein-stimulatory activity. In the case of 2-(3-bromophenyl)histamine, 2-adamantylhistamine and 2-(3-phenylpropyl)histamine, replacement of the aminoethyl group by a hydroxyethyl group at the imidazole greatly reduced GTPase-activating properties, pointing to the importance of the basic domain in the activation process. Unexpectedly, however, in the case of a very lipophilic substituent (heptadecyl chain) the exchange of the aminoethyl group by a hydroxyethyl group had no substantial inhibitory effect, indicating that the presence of a primary amine is not a conditio sine qua non for a substance being a receptor-independent G-protein activator. Concerning histamine H-1-receptors the newly prepared compounds proved to be weak antagonists.
• US4808530A
  申请人：——

  公开号：US4808530A

  公开（公告）日：1989-02-28