5-tert-butyl ester-1-methyl-L-glutamate

• 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: 5-tert-butyl ester-1-methyl-L-glutamate
• 英文别名: 5-(1,1-dimethylethyl)-1-methyl-D-glutamate；(R)-5-tert-Butyl 1-methyl 2-aminopentanedioate；5-O-tert-butyl 1-O-methyl (2R)-2-aminopentanedioate
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: JKIPBZRGKFRHKQ-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-tert-butyl ester-1-methyl-L-glutamate 在 N-甲基吗啉 、 盐酸 、 sodium hydroxide 、 1-羟基苯并三唑 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 氯甲酸异丁酯 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-4-({[(S)-2-((S)-2-Carbamoyl-pyrrolidin-1-yl)-1-(4-nitro-benzyl)-2-oxo-ethylcarbamoyl]-methyl}-carbamoyl)-4-[(S)-2-guanidino-3-(4-hydroxy-phenyl)-propionylamino]-butyric acid
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 1. Polar pentapeptides

  摘要：

  The design, synthesis, and biological activity of a series of highly polar enkephalin-related pentapeptides are reported. These analogues incorporate structural features that exclude them from the central nervous system and thereby restrict their action to peripherally located receptors. Hydrophilic analogues were obtained by introduction of polar D-amino acid residues at position 2 and, in certain cases, by conversion of the N-terminal amino group of the Tyr residue to a guanidino function. The peptides were synthesized by classical solution methods. All compounds demonstrated in vitro opioid activity in the GPI and all were shown to possess antinociceptive activity in chemically induced writhing models. The analgesic effects were shown to be predominantly peripherally mediated by antagonism of antinociception with the peripheral antagonist N-methylnalorphine. Comparative data obtained in writhing and hot-plate tests were also supportive of a peripheral mode of action. Compound 13a, L-tyrosyl-D-arginylglycyl-L-4-nitrophenylalanyl-L-prolinamide (BW 443C), was identified as having a favorable pharmacological profile, indicating a high level of peripheral selectivity, and worthy of further investigation.

  DOI：

  10.1021/jm00400a012
• 作为产物：
  描述：

  D-谷氨酸 在 氯化亚砜 、 三异丙基硅烷 、 水 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 5-tert-butyl ester-1-methyl-L-glutamate
  参考文献：
  名称：

  一种谷氨酸-1-甲酯-5-叔丁酯的合成方法

  摘要：

  本发明公开了一种谷氨酸‑1‑甲酯‑5‑叔丁酯的合成方法，该方法以谷氨酸为起始原料，在甲醇中与氯化亚砜作用下，生成谷氨酸双甲酯；然后将谷氨酸双甲酯与三苯基氯甲烷反应生成氨基被三苯甲基保护的谷氨酸双甲酯，氨基被三苯甲基保护的谷氨酸双甲酯在氢氧化钠的作用下脱掉5位的甲酯，生成三苯甲基‑谷氨酸‑1‑甲酯；三苯甲基‑谷氨酸‑1‑甲酯与三氯乙酰基亚胺叔丁酯反应生成三苯甲基‑谷氨酸‑1‑甲酯‑5‑叔丁酯，三苯甲基‑谷氨酸‑1‑甲酯‑5‑叔丁酯在低浓度的三氟乙酸二氯甲烷溶液中，并加入少量三异丙基硅烷脱掉三苯甲基生成谷氨酸‑1‑甲酯‑5‑叔丁酯。本发明方法操作简单，副产物很少，极易处理，产物产率很高，解决了现有合成方法操作难度大的问题。

  公开号：

  CN109516925B

文献信息

• SUBSTITUTED PIPERIDINES AS CCR3 ANTAGONISTS
  申请人：GRUNDL Marc

  公开号：US20100261687A1

  公开（公告）日：2010-10-14

  Object of the present invention are novel substituted compounds of the formula 1, wherein A, R 1 , R 2 , R 3 and R 4 are defined as in the description. Another object of the present invention is to provide antagonists of CCR3, more particularly to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt thereof.

  本发明的对象是公式1的新型取代化合物，其中A、R1、R2、R3和R4的定义如描述中所述。本发明的另一个对象是提供CCR3的拮抗剂，更具体地提供包含药用可接受载体和本发明化合物中至少一种或其药用可接受盐的治疗有效量的药物组合物。
• CO-CRYSTALS AND SALTS OF CCR3-INHIBITORS
  申请人：Frank Markus

  公开号：US20120264729A1

  公开（公告）日：2012-10-18

  This invention relates to co-crystals and salts of CCR3 inhibitors of formula 1, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases related with the CCR3-receptor.

  本发明涉及公式1的CCR3抑制剂的共晶体和盐，包含相同物质的药物组合物，以及将其用作治疗和/或预防与CCR3受体相关疾病的药剂的方法。
• Glutamic acid derivatives
  申请人：Roussel Uclaf

  公开号：US05089476A1

  公开（公告）日：1992-02-18

  All isomeric forms and mixtures of isomers of glutamic acid compounds of the formula ##STR1## wherein the glutamic aid is of D- or L- configuration, R.sub.1 is selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, an amino acid, a peptide of 2 to 4 amino acids and an amino acid or a peptide of 2 to 4 amino acids in which the amine is esterified with an optionally unsaturated aliphatic carboxylic acid of 6 to 24 carbon atoms or R.sub.1 is selected from the group consisting of a residue of a C.sub.6 -C.sub.24 optionally unsaturated aliphatic acid. R.sub.5 is selected from the group consisting of hydrogen or an alkyl radical of 1 to 5 carbon atoms, R.sub.3 is selected from the group consisting of hydroxy, alkoxy of 1 to 5 carbon atoms, an amino acid with the amine optionally substituted with alkyl of 1 to 5 carbon atoms, Z is ##STR2## R.sub.2 is selected from the group consisting of hydrogen, an amino acid and a peptide of 2 to 4 amino acids, R.sub.4 is selected from the group consisting of hydroxy, alkoxy 1 to 5 carbon atoms and an amino acid optionally substituted on the amine with alkyl of 1 to 5 carbon atoms, U is selected from the group consisting of ##STR3## --CH.dbd.CH--CH.sub.2 -- (E or Z isomer), --CH.sub.2 --CH.dbd.CH-- (E or Z isomer) and ##STR4## or U and Y together are .dbd.CH--CH.sub.2 --CH.sub.2 -- (E or Z isomer) and X is hydrogen and their salts with non-toxic, pharmaceutically acceptable acid or bases having immunomodulatory properties.

  谷氨酸化合物的所有异构体和异构体混合物的公式为 ##STR1##，其中谷氨酸为D或L构型，R.sub.1从由氢，1至5个碳原子的烷基，氨基酸，2至4个氨基酸的肽以及氨基酸或2至4个氨基酸的肽中选择，其中胺基与6至24个碳原子的可选不饱和脂肪酸酯化或R.sub.1从由C.sub.6-C.sub.24可选不饱和脂肪酸的残基中选择。R.sub.5从氢或1至5个碳原子的烷基基团中选择，R.sub.3从羟基，1至5个碳原子的烷氧基，胺基酸以胺基可选地被1至5个碳原子的烷基取代的羟基，Z为 ##STR2##，R.sub.2从氢，氨基酸和2至4个氨基酸的肽中选择，R.sub.4从羟基，1至5个碳原子的烷氧基和氨基酸中选择，该氨基酸在胺基上可选地用1至5个碳原子的烷基取代，U从 ##STR3##，--CH.dbd.CH--CH.sub.2 --（E或Z异构体），--CH.sub.2 --CH.dbd.CH--（E或Z异构体）和 ##STR4## 中选择，或U和Y一起为.dbd.CH--CH.sub.2 --CH.sub.2 --（E或Z异构体），X为氢，以及它们与无毒、药理学上可接受的酸或碱的盐，具有免疫调节作用。
• Therapeutic methods employing substituted piperidines which are CCR3 antagonists
  申请人：GRUNDL Marc

  公开号：US20130023517A1

  公开（公告）日：2013-01-24

  Object of the present invention are novel substituted compounds of the formula 1, wherein A, R 1 , R 2 , R 3 and R 4 are defined as in the description. Another object of the present invention is to provide antagonists of CCR3, more particularly to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt thereof.

  本发明的目的是提供公式1的新型取代化合物，其中A、R1、R2、R3和R4的定义如描述中所述。本发明的另一个目的是提供CCR3的拮抗剂，更具体地提供包含药学上可接受的载体和本发明化合物中至少一种或其药学上可接受的盐的治疗有效量的制药组合物。
• AGOURIDAS, CONSTANTIN;DAMAIS, CHANTAL;FAUVEAU, PATRICK
  作者：AGOURIDAS, CONSTANTIN、DAMAIS, CHANTAL、FAUVEAU, PATRICK

  DOI：——

  日期：——