diethyl acetamido(5-bromopentyl)malonate | 5183-26-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: diethyl acetamido(5-bromopentyl)malonate
• 英文别名: (5-Brom-pentyl)-acetamino-malonsaeure-diaethylester；Propanedioic acid, (acetylamino)(5-bromopentyl)-, diethyl ester；diethyl 2-acetamido-2-(5-bromopentyl)propanedioate
• CAS: 5183-26-6
• 化学式: C₁₄H₂₄BrNO₅
• 分子量: 366.252
• InChiKey: MTUPFTCWXFJLCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2924199090

反应信息

• 作为反应物：
  描述：

  diethyl acetamido(5-bromopentyl)malonate 在 盐酸 、 sodium hydride 作用下， 反应 21.25h， 生成 methyl 2-amino-7-<(2-hydroxyphenyl)thio>heptanoate
  参考文献：
  名称：

  A unified approach to systematic isosteric substitution for acidic groups and application to NMDA antagonists related to 2-amino-7-phosphonoheptanoate

  摘要：

  A systematic approach to the replacement of acidic groups with potential bioisosteres is described. The strategy involves simple nucleophilic displacement of a common alkyl halide precursor with a variety of mercaptoazoles and related molecules. The mercaptoazoles and their oxidized derivatives (sulfinyl- and sulfonylazoles) represent a series of possible surrogates for acidic groups which span a pKa range from about 4.5-11.5. This simple strategy was extended to include 2-hydroxy- or 2-aminothiophenyl groups which function as relatively nonacidic isosteres for a phosphonic acid. By replacing the phosphonic acid of 2-amino-7-phosphonoheptanoate (AP-7) with these groups, we have synthesized novel N-methyl-d-aspartate (NMDA) antagonists.

  DOI：

  10.1021/jm00165a030
• 作为产物：
  描述：

  1,5-二溴戊烷 、 乙酰氨基丙二酸二乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 diethyl acetamido(5-bromopentyl)malonate
  参考文献：
  名称：

  用 [99mTc(CO)3]+ 标记并被 1 型氨基酸转运蛋白 LAT1 识别的氨基酸

  摘要：

  我们已经合成了通过烷基间隔与小三脚架配体在 α-碳上共轭的氨基酸。三脚架坐标到 fac-[M(CO)3]+ 部分（M = Re，99mTc）。根据间隔物的长度，这些带有悬垂α-氨基酸的金属复合物被l型氨基酸转运蛋白LAT1识别和转运。最好的结果是使用丁基间隔物实现的。相应复合物的 Ki 值与人工氨基酸 BCH 的 Ki 值相当。[3H]-l-苯丙氨酸的流出表明标记的氨基酸不仅与转运蛋白结合，而且被转运到细胞中。这些是第一个被积极内化到细胞内空间的金属标记的小分子。

  DOI：

  10.1021/ja066002m

文献信息

• Double-Headed Sulfur-Linked Amino Acids As First Inhibitors for Betaine-Homocysteine <i>S</i>-Methyltransferase 2
  作者：Jana Mládková、Václav Vaněk、Miloš Buděšínský、Tomáš Elbert、Zuzana Demianová、Timothy A. Garrow、Jiří Jiráček

  DOI：10.1021/jm300571h

  日期：2012.8.9

  Betaine-homocysteine S-methyltransferase 2 (BHMT-2) catalyzes the transfer of a methyl group from S-methylmethionine to l-homocysteine, yielding two molecules of l-methionine. It is one of three homocysteine methyltransferases in mammals, but its overall contribution to homocysteine remethylation and sulfur amino acid homeostasis is not known. Moreover, recombinant BHMT-2 is highly unstable, which

  甜菜碱-高半胱氨酸的S-甲基转移酶2（BHMT-2）催化甲基从S-甲基甲硫氨酸向1-高半胱氨酸的转移，产生两个分子的1-甲硫氨酸。它是哺乳动物中三种同型半胱氨酸甲基转移酶之一，但其对同型半胱氨酸再甲基化和硫氨基酸稳态的总体贡献尚不清楚。而且，重组BHMT-2是高度不稳定的，这减慢了其结构和催化性能的研究。在这项研究中，我们准备了将要描述的第一批BHMT-2抑制剂，并已通过与人重组BHMT共纯化而稳定的人重组BHMT-2对其进行了测试。在合成的化合物中，（2 S，8RS，11 RS）-5-硫杂-2,11-二氨基-8-甲基十二烷二酸（11）是最有效的（K i app约为77 nM）和BHMT-2的选择性抑制剂。化合物11仅弱抑制人BHMT（IC 50约为77μM ）。该化合物（11）可用于将来的体内研究中，以探测BHMT-2在硫氨基酸代谢中的生理意义。
• Synthesis of l-α-amino-ω-bromoalkanoic acid for side chain modification
  作者：Louis A. Watanabe、Binoy Jose、Tamaki Kato、Norikazu Nishino、Minoru Yoshida

  DOI：10.1016/j.tetlet.2003.11.007

  日期：2004.1

  l-α-Amino-ω-bromoalkanoic acids with side chain lengths varying from 4 to 10 methylene units have been conveniently synthesized as useful intermediates for the synthesis of functionalized non-natural amino acids.

  侧链长度在4至10个亚甲基单元之间变化的1-α-氨基-ω-溴链烷酸已经方便地合成为有用的中间体，用于合成官能化的非天然氨基酸。
• The synthesis of specifically14C-labelled 2,6-diaminopimelic acid and its higher homologues
  作者：J. Hanuš、K. Vereš

  DOI：10.1002/jlcr.2590060205

  日期：1970.4

  D,L-2,6-Diaminopimelic-(2-14C) acid was prepared by alkylation of diethyl acetamidomalonate-(2-14C) with 5-bromo-N-phthaloyl-L-norvaline methyl ester and hydrolysis of the condensation product. Depending on the alkylation conditions, partial or complete racemisation takes place and therefore the L,L-form of diaminopimelic acid had to be isolated by paper chromatography. Alkylation of diethyl acetamidomalonate-(2-14C) with diethyl 4-bromobutyl- or 5-bromopentyl- or 6-bromohexylacetamidomalonate and subsequent hydrolysis of the condensation products gave D,L-2,7-diamino-suberic-(2-14C), D,L-2,8-diaminoazelaic-2-14C, and D,L-2,8-diaminosebacic-(2-14C) acids respectively.

  D,L-2,6-二氨基丙二酸-(2-14C)是通过乙酰氨基丙二酸二乙酯-(2-14C)与 5-溴-N-邻苯二甲酰-L-正缬氨酸甲酯的烷基化反应以及缩合产物的水解反应制备的。根据烷基化条件的不同，会发生部分或完全消旋化，因此必须通过纸色谱法分离 L,L-形式的二氨基丙二酸。乙酰氨基丙二酸二乙酯-(2-14C)与 4-溴丁基-或 5-溴戊基-或 6-溴己基乙酰氨基丙二酸二乙酯烷基化，然后水解缩合产物，分别得到 D,L-2,7-二氨基丁二酸-(2-14C)、D,L-2,8-二氨基壬二酸-(2-14C)和 D,L-2,8-二氨基二十二酸-(2-14C)。
• ST7612AA1, a Thioacetate-ω(γ-lactam carboxamide) Derivative Selected from a Novel Generation of Oral HDAC Inhibitors
  作者：Giuseppe Giannini、Loredana Vesci、Gianfranco Battistuzzi、Davide Vignola、Ferdinando M. Milazzo、Mario Berardino Guglielmi、Marcella Barbarino、Mosè Santaniello、Nicola Fantò、Marco Mor、Silvia Rivara、Daniele Pala、Maurizio Taddei、Claudio Pisano、Walter Cabri

  DOI：10.1021/jm5008209

  日期：2014.10.23

  A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ?-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ?-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.
• Rozhko; Ragulin; Tsvetkov, Russian Journal of General Chemistry, 1997, vol. 67, # 12, p. 1861 - 1863
  作者：Rozhko、Ragulin、Tsvetkov

  DOI：——

  日期：——