(+)-(S)-valylglycine methyl ester hydrochloride | 2421-57-0

• 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: (+)-(S)-valylglycine methyl ester hydrochloride
• 英文别名: L-valylglycine methyl ester hydrochloride；H-Val-Gly-OMe*HCl；methyl 2-[[(2S)-2-amino-3-methylbutanoyl]amino]acetate;hydrochloride
• CAS: 2421-57-0
• 化学式: C₈H₁₆N₂O₃*ClH
• 分子量: 224.688
• InChiKey: VVAGYMMJAMALGJ-FJXQXJEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.32
• 重原子数：
  14.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  81.42
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (+)-(S)-valylglycine methyl ester hydrochloride 在 lithium hydroxide monohydrate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  JD-5006 and JD-5037: Peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities

  摘要：

  Analogs of SLV-319 (Ibipinibant), a CB1 receptor inverse agonist, were synthesized with functionality intended to limit brain exposure while maintaining the receptor affinity and selectivity of the parent compound. Structure activity relationships of this series, and pharmacology of two lead compounds, 16 (JD-5006) and 23 (JD-5037) showing little brain presence as indicated by tissue distribution and receptor occupancy studies, are described. Effects with one of these compounds on plasma triglyceride levels, liver weight and enzymes, glucose tolerance and insulin sensitivity support the approach that blockade of peripheral CB1 receptors is sufficient to produce many of the beneficial metabolic effects of globally active CB1 blockers. Thus, PR CB1 inverse agonists may indeed represent a safer alternative to highly brain-penetrant agents for the treatment of metabolic disorders, including diabetes, liver diseases, dyslipidemias, and obesity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.004
• 作为产物：
  描述：

  N-benzyloxycarbonylvalylglycine methyl ester 在 盐酸 、 氢气 、 溶剂黄146 作用下， 以 水 为溶剂， 生成 (+)-(S)-valylglycine methyl ester hydrochloride
  参考文献：
  名称：

  Hydantoin-Free Synthesis of Peptide Ester Isocyanates, Isothiocyanates, and Dipeptidyl Ureas: The Application of Zinc Dust in a Carbonylation Procedure without Base

  摘要：

  在使用活性锌粉作为非碱性HCl清除剂的情况下，描述了无需使用海因（hydantoin）的肽酯异氰酸酯自由合成方法，即非Schotten-Baumann条件。此外，在将氨基酸和肽酰胺转化为异氰酸酯的过程中，该方法不会产生N-酰化产物。

  DOI：

  10.1055/s-0030-1260216

文献信息

• Amino acids and peptides. XXVIII. Synthesis of peptide fragments related to eglin c and studies on the relationship between their structure and effects on human leukocyte elastase, cathepsin G and .ALPHA.-chymotrypsin.
  作者：Satoshi TSUBOI、Kazunori NAKABAYASHI、Yoshikazu MATSUMOTO、Naoki TENO、Yuko TSUDA、Yoshio OKADA、Yoko NAGAMATSU、Junichiro YAMAMOTO

  DOI：10.1248/cpb.38.2369

  日期：——

  Various peptide fragments related to eglin c, which consists of 70 amino acid residues, were synthesized by a conventional solution method and their inhibitory effects on leukocyte elastase, cathepsin G and α-chymotrypsin were examined. Among them, H-Arg-Glu-Tyr-Phe-OMe (eglin c 22-25) and H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OMe (eglin c 41-49) inhibited cathepsin G and α-chymotrypsin but not leukocyte elastase, while H-Thr-Asn-Val-Val-OMe (eglin c 60-63) inhibited leukocyte elastase but not cathepsin G or α-chymotrypsin, although eglin c potently inhibited leukocyte elastase, cathepsin G and α-chymotrypsin. These results indicated that the interaction sites of eglin c with leukocyte elastase, cathepsin G and α-chymotrypsin might be different.

  采用常规的溶液法合成了与来自家蚕血淋巴的抗蛋白酶eglin c（由70个氨基酸残基构成）相关的各种肽片段，并检验了它们对白细胞弹性蛋白酶、组织蛋白酶G和α-胰凝乳蛋白酶的抑制效应。其中，H-Arg-Glu-Tyr-Phe-OMe（eglin c 22-25）和H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OMe（eglin c 41-49）能抑制组织蛋白酶G和α-胰凝乳蛋白酶，但不能抑制白细胞弹性蛋白酶，而H-Thr-Asn-Val-Val-OMe（eglin c 60-63）能抑制白细胞弹性蛋白酶，但不能抑制组织蛋白酶G或α-胰凝乳蛋白酶，尽管eglin c对白细胞弹性蛋白酶、组织蛋白酶G和α-胰凝乳蛋白酶都具有强抑制作用。这些结果提示，eglin c与白细胞弹性蛋白酶、组织蛋白酶G和α-胰凝乳蛋白酶的相互作用部位可能各不相同。
• Kashima, Choji; Maruyama, Tatsuya; Harada, Kazuo, Journal of Chemical Research, Miniprint, 1988, # 2, p. 601 - 645
  作者：Kashima, Choji、Maruyama, Tatsuya、Harada, Kazuo、Hibi, Shigeki、Omote, Yoshimori

  DOI：——

  日期：——
• Neighboring residue effects: evidence for intramolecular assistance to racemization or epimerization of dipeptide residues
  作者：Grant Gill. Smith、Robert C. Evans、Rocky. Baum

  DOI：10.1021/ja00283a031

  日期：1986.11
• Davies, John S.; Enjalbal, Christine; Llewellyn, Gareth, Journal of the Chemical Society. Perkin transactions II, 1992, # 8, p. 1225 - 1231
  作者：Davies, John S.、Enjalbal, Christine、Llewellyn, Gareth

  DOI：——

  日期：——
• 2-Oxoamide inhibitors of phospholipase A2 activity and cellular arachidonate release based on dipeptides and pseudodipeptides
  作者：Efrosini Barbayianni、Daren Stephens、Andrej Grkovich、Victoria Magrioti、Yuan-Hao Hsu、Panagiotis Dolatzas、Dimitrios Kalogiannidis、Edward A. Dennis、George Kokotos

  DOI：10.1016/j.bmc.2009.03.069

  日期：2009.7

  A series of 2-oxoamides based on dipeptides and pseudodipeptides were synthesized and their activities towards two human intracellular phospholipases A(2) (GIVA cPLA(2) and GVIA iPLA(2)) and one human secretory phospholipase A(2) (GV sPLA(2)) were evaluated. Derivatives containing a free carboxyl group are selective GIVA cPLA(2) inhibitors. A derivative based on the ethyl ester of an ether pseudodipeptide is the first 2-oxoamide, which preferentially inhibits GVIA iPLA2. The effect of 2-oxoamides on the generation of arachidonic acid from RAW 264.7 macrophages was also studied and it was found that selective GIVA cPLA(2) inhibitors preferentially inhibited cellular arachidonic acid release; one pseudodipeptide gave an IC50 value of 2 mu M. (C) 2009 Elsevier Ltd. All rights reserved.