N_α-Cbz-N_ε-Boc-lysyl chloromethane | 138849-01-1

• 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: N_α-Cbz-N_ε-Boc-lysyl chloromethane
• 英文别名: Z-Lys(Boc)-CH2Cl；benzyl tert-butyl (7-chloro-6-oxoheptane-1,5-diyl) (S)-dicarbamate；benzyl N-[(3S)-1-chloro-7-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxoheptan-3-yl]carbamate
• CAS: 138849-01-1
• 化学式: C₂₀H₂₉ClN₂O₅
• 分子量: 412.914
• InChiKey: MJUXZSHWWNNNBF-INIZCTEOSA-N

物化性质

• 沸点：
  594.0±50.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.78
• 重原子数：
  28.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  93.73
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N_α-Cbz-N_ε-Boc-lysyl chloromethane 在 sodium tetrahydroborate 、 sodium methylate 作用下， 以 甲醇 、 乙醇 为溶剂， 生成
  参考文献：
  名称：

  功能化的赤型N-保护的α-氨基环氧化物。立体控制的合成和生物活性

  摘要：

  合成了由带有官能化侧链的α-氨基酸衍生的Eththro N-保护的α-氨基环氧化物。关键的合成步骤是将相应的卤代化合物立体选择性地还原为卤代醇或直接还原为环氧化物。侧链包括分别衍生自天冬氨酸和谷氨酸，丝氨酸，精氨酸和赖氨酸的酯，醚和醇，硝基胍，氨基甲酸酯和胺官能团。从赖氨酸和衍生环氧化物Ñ π硝基精氨酸表现出半胱氨酸蛋白酶木瓜蛋白酶和组织蛋白酶B的选择性失活，而他们没有失活的丝氨酸蛋白酶胰蛋白酶。

  DOI：

  10.1016/s0040-4020(97)00195-6
• 作为产物：
  描述：

  重氮甲烷 、 Nε-Boc-Nα-Cbz-L-赖氨酸 生成 N_α-Cbz-N_ε-Boc-lysyl chloromethane
  参考文献：
  名称：

  功能化的赤型N-保护的α-氨基环氧化物。立体控制的合成和生物活性

  摘要：

  合成了由带有官能化侧链的α-氨基酸衍生的Eththro N-保护的α-氨基环氧化物。关键的合成步骤是将相应的卤代化合物立体选择性地还原为卤代醇或直接还原为环氧化物。侧链包括分别衍生自天冬氨酸和谷氨酸，丝氨酸，精氨酸和赖氨酸的酯，醚和醇，硝基胍，氨基甲酸酯和胺官能团。从赖氨酸和衍生环氧化物Ñ π硝基精氨酸表现出半胱氨酸蛋白酶木瓜蛋白酶和组织蛋白酶B的选择性失活，而他们没有失活的丝氨酸蛋白酶胰蛋白酶。

  DOI：

  10.1016/s0040-4020(97)00195-6

文献信息

• Development of Active Center-Directed Inhibitors against Plasmin.
  作者：Naoki TENO、Keiko WANAKA、Yoshio OKADA、Yuko TSUDA、Utako OKAMOTO、Akiko HIJIKATA-OKUNOMIYA、Taketoshi NAITO、Shosuke OKAMOTO

  DOI：10.1248/cpb.39.2340

  日期：——

  Active center-directed inhibitors of plasmin were designed based on the structure of specific substrates of plasmin and then synthesized. Their effects on plasmin were examined and the structure-inhibitory activity relationship was studied. Nα-trans-4-Aminomethylcyclohexanecarbonyllysine 4-benzoylanilide (Tra-Lys-BZA) inhibited plasmin activities toward S-2251 and fibrin with IC50 values of 15 and 6.1 μM, respectively and Nα-trans-4-aminomethylcyclohexanecarbonyllysine 4-benzylpiperidine amide (Tra-Lys-BPP) did not show any detectable inhibitory activity. Moreover, it was revealed that Tra-Lys-4-methoxycarbonylanilide inhibited plasma kallikrein more potently than plasmin.

  基于纤溶酶的特定底物结构设计了活性中心导向的纤溶酶抑制剂，并进行了合成。研究了它们对纤溶酶的效应以及结构-抑制活性的关系。Nα-反式-4-氨甲基环己烷羰基赖氨酸4-苯甲酰苯胺（Tra-Lys-BZA）对S-2251和纤维蛋白的IC50值分别为15和6.1μM，而Nα-反式-4-氨甲基环己烷羰基赖氨酸4-苄基哌啶酰胺（Tra-Lys-BPP）则没有显示出任何可检测的抑制活性。此外，研究发现Tra-Lys-4-甲氧羰基苯胺对血浆激肽释放酶的抑制作用比纤溶酶更强。
• Expanding the scope of PNA-encoded libraries: divergent synthesis of libraries targeting cysteine, serine and metallo-proteases as well as tyrosine phosphatases
  作者：François Debaene、Julien A. Da Silva、Zbigniew Pianowski、Fernando J. Duran、Nicolas Winssinger

  DOI：10.1016/j.tet.2007.03.033

  日期：2007.7

  Seven PNA-encoded combinatorial libraries targeting proteases and phosphatases with covalent reversible and irreversible mechanism-based inhibitors were prepared. The libraries were synthesized using modified PNA monomers, which dramatically increase the water solubility of the libraries in biologically relevant buffers. The libraries were shown to selectively inhibit targeted enzymes. (c) 2007 Elsevier Ltd. All rights reserved.
• Oral Bioavailability of a New Class of μ-Opioid Receptor Agonists Containing 3,6-Bis[Dmt-NH(CH₂)<i>_n</i>]-2(1<i>H</i>)-pyrazinone with Central-Mediated Analgesia
  作者：Yunden Jinsmaa、Anna Miyazaki、Yoshio Fujita、Tingyou Li、Yutaka Fujisawa、Kimitaka Shiotani、Yuko Tsuda、Toshio Yokoi、Akihiro Ambo、Yusuke Sasaki、Sharon D. Bryant、Lawrence H. Lazarus、Yoshio Okada

  DOI：10.1021/jm0304616

  日期：2004.5.1

  The inability of opioid peptides to be transported through epithelial membranes in the gastrointestinal tract and pass the blood-brain barrier limits their effectiveness for oral application in an antinociceptive treatment regime. To overcome this limitation, we enhanced the hydrophobicity while maintaining the aqueous solubility properties in a class of opioidmimetic substances by inclusion of two identical N-termini consisting of Dmt (2',6'-dimethyl-L-tyrosine) coupled to a pyrazinone ring platform by means of alkyl chains to yield the class of 3,6-bis[Dmt-NH-(CH2)(n)],1-2(1H)-pyrazinones. These compounds displayed high mu-opioid receptor affinity (K(i)mu = 0.042-0.115 nM) and selectivity (K(i)delta/K(i)mu = 204-307) and functional p-opioid receptor agonism (guinea-pig ileum, IC50 = 1.3-1.9 nM) with little or undetectable bioactivity toward delta-opioid receptors (mouse vas deferens) and produced analgesia in mice in a naloxone reversible manner when administered centrally (intracerebroventricular, icv) or systemically (subcutaneously and orally). Furthermore, the most potent compound, 3,6-bis(3'-Dmt-aminopropyl)-5-methyl-2(1H)-pyrazinone (7') lacked functional delta-opioid receptor bioactivity and was 50-63-fold and 18-21-fold more active than morphine by icv administration as measured analgesia using tail-flick (spinal involvement) and hot-plate (supraspinal effect) tests, respectively; the compound ranged from 16 to 63% as potent upon systemic injection. These analgesic effects are many times greater than unmodified opioid peptides. The data open new possibilities for the rational design of potential opioid-mimetic drugs that pass through the epithelium of the gastrointestinal tract and the blood-brain barrier to target brain receptors.