methyl (4R)-4-amino-6-methylheptanoate hydrochloride

• 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: methyl (4R)-4-amino-6-methylheptanoate hydrochloride
• 英文别名: HCl*H₂N-(R)-γ⁴-Leu-OMe；methyl (4R)-4-amino-6-methylheptanoate;hydrochloride
• 化学式: C₉H₁₉NO₂*ClH
• 分子量: 209.716
• InChiKey: GIKQXBLQFZNVMX-DDWIOCJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.73
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (4R)-4-amino-6-methylheptanoate hydrochloride 在 碳酸氢钠 4-acetylamino-2,2,6,6-tetramethylpiperidine-N-oxyl 、 sodium hydroxide 、 sodium hypochlorite 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium bromide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 13.25h， 生成 (R)-6-Methyl-4-(2-oxo-pentadecanoylamino)-heptanoic acid
  参考文献：
  名称：

  Inhibition of Group IVA Cytosolic Phospholipase A₂ by Novel 2-Oxoamides in Vitro, in Cells, and in Vivo

  摘要：

  The Group IVA cytosolic phospholipase A(2) (GIVA PLA(2)) is a particularly attractive target for drug development because it is the rate-limiting provider of proinflammatory mediators. We previously reported the discovery of novel 2-oxoamides that inhibit GIVA PLA(2) [Kokotos, G.; et al. J. Med. Chem. 2002, 45, 2891-2893]. In the present work, we have further explored this class of inhibitors and found that the 2-oxoamide functionality is more potent when it contains a long 2-oxoacyl residue and a free carboxy group. Long-chain 2-oxoamides based on gamma-aminobutyric acid and gamma-norleucine are potent inhibitors of GIVA PLA(2). Such inhibitors act through a fast and reversible mode of inhibition in vitro, are able to block the production of arachidonic acid and prostaglandin E-2 in cells, and demonstrate potent in vivo antiinflammatory and analgesic activity.

  DOI：

  10.1021/jm030485c
• 作为产物：
  描述：

  2-甲基-2-丙基[(2S)-4-甲基-1-氧代-2-戊烷基]氨基甲酸酯 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.5h， 生成 methyl (4R)-4-amino-6-methylheptanoate hydrochloride
  参考文献：
  名称：

  Inhibition of Group IVA Cytosolic Phospholipase A₂ by Novel 2-Oxoamides in Vitro, in Cells, and in Vivo

  摘要：

  The Group IVA cytosolic phospholipase A(2) (GIVA PLA(2)) is a particularly attractive target for drug development because it is the rate-limiting provider of proinflammatory mediators. We previously reported the discovery of novel 2-oxoamides that inhibit GIVA PLA(2) [Kokotos, G.; et al. J. Med. Chem. 2002, 45, 2891-2893]. In the present work, we have further explored this class of inhibitors and found that the 2-oxoamide functionality is more potent when it contains a long 2-oxoacyl residue and a free carboxy group. Long-chain 2-oxoamides based on gamma-aminobutyric acid and gamma-norleucine are potent inhibitors of GIVA PLA(2). Such inhibitors act through a fast and reversible mode of inhibition in vitro, are able to block the production of arachidonic acid and prostaglandin E-2 in cells, and demonstrate potent in vivo antiinflammatory and analgesic activity.

  DOI：

  10.1021/jm030485c

文献信息

• An α-Helix-Mimicking 12,13-Helix: Designed α/β/γ-Foldamers as Selective Inhibitors of Protein-Protein Interactions
  作者：Claire M. Grison、Jennifer A. Miles、Sylvie Robin、Andrew J. Wilson、David J. Aitken

  DOI：10.1002/anie.201604517

  日期：2016.9.5

  interactions (PPIs). In this work, trans‐2‐aminocyclobutanecarboxylic acid (tACBC) was used as the key β‐amino acid component in the design of α/β/γ‐peptides to structurally mimic a native α‐helix. Suitably functionalized α/β/γ‐peptides assume an α‐helix‐mimicking 12,13‐helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild‐type α‐peptide parent sequence from which

  当前生物有机化学的一个主要挑战是鉴定蛋白质二级结构的有效模拟物，作为蛋白质-蛋白质相互作用（PPI）的抑制剂。在这项工作中，反式-2-氨基环丁烷甲酸（ t ACBC）被用作α/β/ γ-肽设计中的关键β-氨基酸成分，以在结构上模拟天然的α-螺旋。适当功能化的 α/β/γ-肽在溶液中呈现模拟 12,13-螺旋构象的 α-螺旋，与衍生它们的野生型 α-肽亲本序列相比，表现出增强的蛋白水解稳定性，并充当p53/ h DM2 相互作用的选择性抑制剂。
• Betulinic Acid Derivatives:  A New Class of Specific Inhibitors of Human Immunodeficiency Virus Type 1 Entry
  作者：Françoise Soler、Christèle Poujade、Michel Evers、Jean-Christophe Carry、Yvette Hénin、Anne Bousseau、Thierry Huet、Rudi Pauwels、Erik De Clercq、Jean-François Mayaux、Jean-Bernard Le Pecq、Norbert Dereu

  DOI：10.1021/jm950669u

  日期：1996.1.1

  A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. ''Time of addition'' experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.
• C₁₂ Helices in Long Hybrid (αγ)_<i>n</i> Peptides Composed Entirely of Unconstrained Residues with Proteinogenic Side Chains
  作者：Rajesh Sonti、Bhimareddy Dinesh、Krishnayan Basuroy、Srinivasarao Raghothama、Narayanaswamy Shamala、Padmanabhan Balaram

  DOI：10.1021/ol500307p

  日期：2014.3.21

  Unconstrained gamma(4) amino acid residues derived by homologation of proteinogenic amino acids facilitate helical folding in hybrid (alpha gamma)(n) sequences. The C-12 helical conformation for the decapeptide, Boc-[Leu-gamma(4)(R)Val](5)-OMe, is established in crystals by X-ray diffraction. A regular C-12 helix is demonstrated by NMR studies of the 18 residue peptide, Boc-[Leu-gamma(4)(AR)Val](9)-OMe, and a designed 16 residue (alpha gamma)(n) peptide, incorporating variable side chains. Unconstrained (alpha gamma)(n) peptides show an unexpectedly high propensity for helical folding in long polypeptide sequences.
• Phospholipase A2 Inhibitors and their Use in Treating Neurological Injury and Disease
  申请人：Dennis Edward A.

  公开号：US20110105610A1

  公开（公告）日：2011-05-05

  Phospholipase A 2 (PLA 2 ) forms are expressed in spinal cord whose inhibition induces a potent antihyperalgesia. PLA 2 inhibitor compounds are provided that include a common motif consisting of a 2-oxoamide with a hydrocarbon tail and a four carbon tether. The compounds block Group IVA calcium dependent PLA 2 (cPLA 2 ) and/or Group VIA calcium independent PLA 2 (iPLA 2 ) and/or Group V secreted PLA 2 (sPLA 2 ). Pharmaceutical compositions of compounds having cPLA 2 inhibitory activity (but not iPLA 2 or sPLA 2 inhibitory activity) are useful in treating multiple sclerosis, while compositions of compounds having sPLA 2 inhibitory activity (as well as iPLA 2 and CPLA 2 activity) are useful in treating spinal cord injuries (with related functional recovery).
• US8420852B2
  申请人：——

  公开号：US8420852B2

  公开（公告）日：2013-04-16