ethyl N-cyclooctylglycinate | 127413-63-2

• 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: ethyl N-cyclooctylglycinate
• 英文别名: N-(cyclooctyl)glycine ethyl ester；N-Cyclooctylglycine ethyl ester；ethyl 2-(cyclooctylamino)acetate
• CAS: 127413-63-2
• 化学式: C₁₂H₂₃NO₂
• mdl: MFCD11152064
• 分子量: 213.32
• InChiKey: QUSUSHIFTTYNQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.916
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl N-cyclooctylglycinate 在 氢氧化钾 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 ((S)-1-{Cyclooctyl-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Inhibition of human leukocyte elastase (HLE) by N-substituted peptidyl trifluoromethyl ketones

  摘要：

  A series of tripeptides possessing trifluoromethyl or aryl ketone residues at P1 were prepared and evaluated both in vitro and in vivo as potential inhibitors of human leukocyte elastase (HLE). Tripeptides containing non naturally occurring N-substituted glycine residues at the P2-position have been demonstrated to be potent in vitro inhibitors of HLE, with IC50 values in the submicromolar range. Sterically demanding substituents on the P2-nitrogen have no detrimental effect on in vitro potency. The inhibition process presumably acts via hemiketal formation with the active site Ser195 of HLE, and is facilitated by the strongly electron withdrawing trifluoromethyl functionality. Deletion of the amino acid at the P3-subsite region affords inactive compounds. Valine is the preferred residue at the P1-position, whereas the corresponding glycine, alanine, alpha,alpha-dimethylglycine, or phenylalanine analogues are all inactive. The compounds described herein all confer a high degree of in vitro specificity when tested against representative cysteine, aspartyl, metallo, and other serine proteases. One of the most potent in vitro inhibitors is (3RS)-N-[4-[[[(4-chlorophenyl)sulfonyl]amino]carbonyl]phenyl]oxomethyl]-L-valyl-N-(2,3-dihydro-1H-inden-2-yl)glycine N-[3-(1,1,1-trifluoro-4-methyl-2-oxopentyl)]amide (20i; BI-RA-260) (IC50 = 0.084-mu-M). Compound 20i was also tested in hamsters in an elastase-induced pulmonary hemorrhage (EPH) model. In this model, intratracheal (it.) administration of 20i, 5 min prior to HLE challenge, effectively inhibited hemorrhage in a dose-dependent manner with an ED50 of 4.8-mu-g. The inhibitor 20i, 20-mu-g administered it. 24, 48, and 72 h prior to HLE challenge, exhibits significant inhibition against hemorrhage at all time points (97%, 64% and 49%, respectively). In a 21-day chronic model of emphysema in hamsters, 200-mu-g of HLE administered it. caused an elastase-induced emphysema in the lungs which can be quantitated histologically utilizing image analysis. In this assay, 20i significantly inhibited pulmonary lesions associated with septal destruction and increased alveolar spaces, when dosed at 20-mu-g it. 5 min prior to challenge with HLE.

  DOI：

  10.1021/jm00082a005
• 作为产物：
  描述：

  环辛酮 、 甘氨酸乙酯盐酸盐 在 盐酸 、 sodium cyanoborohydride 作用下， 以 乙醇 、 水 为溶剂， 生成 ethyl N-cyclooctylglycinate
  参考文献：
  名称：

  Imidazo[1,2-a]piperazines

  摘要：

  咪唑-[1,2-a]哌嗪类化合物，是人类中性粒细胞弹性蛋白酶的抑制剂，具有以下一般结构##STR1##其中取代基如下所定义。

  公开号：

  US05166154A1

文献信息

• Angiotensin-converting enzyme inhibitors: Synthesis and structure-activity relationships of potent N-benzyloxycarbonyl tripeptide inhibitors.
  作者：Tadahiro SAWAYAMA、Masatoshi TSUKAMOTO、Takashi SASAGAWA、Kazuya NISHIMURA、Ryuichi YAMAMOTO、Takashi DEGUCHI、Kunihiko TAKEYAMA、Kanoo HOSOKI

  DOI：10.1248/cpb.37.2417

  日期：——

  (Z) tripeptide inhibitors of angiotensin-converting enzyme (ACE) was synthesized. The effect of varying the antepenultimate amino acid residue in this series on the biological activity was studied. Introduction of Lys and Orn residues at the P1 position provided the most potent inhibitors, 25a and 25b (IC50: 3.5 and 4.9 x 10(-9) M, respectively), which exhibited an oral antihypertensive activity. This

  合成了一系列新的含γ-D-Glu的血管紧张素转化酶（ACE）的N-苄氧基羰基（Z）三肽抑制剂。研究了改变该系列中前倒数第二个氨基酸残基对生物活性的影响。在P1位置引入Lys和Orn残基可提供最有效的抑制剂25a和25b（IC50：分别为3.5和4.9 x 10（-9）M），具有口服降压活性。该结果表明，在该系列中，P1位的碱性氨基酸残基在与ACE的S1亚位点的结合中起重要作用。评价了所选化合物的口服降压活性。
• Alkali-metal hexamethyldisilazide initiated polymerization on alpha-amino acid N-substituted N-carboxyanhydrides for facile polypeptoid synthesis
  作者：Yueming Wu、Min Zhou、Kang Chen、Sheng Chen、Ximian Xiao、Zhemin Ji、Jingcheng Zou、Runhui Liu

  DOI：10.1016/j.cclet.2021.02.039

  日期：2021.5

  been explored as mimics of polypeptides, owing to polypeptoids’ superior stability upon proteolysis. Polypeptoids can be synthesized from one-pot ring-opening polymerization of amino acid N-substituted N-carboxyanhydrides (NNCAs). However, the speed of polymerization of NNCAs can be very slow, especially for NNCAs bearing a bulky N-substitution group. This hindered the exploration on polypeptoids with

  由于多肽类在蛋白水解时具有优越的稳定性，因此多肽类被作为多肽的模拟物进行了研究。可以从氨基酸N-取代的N-羧基酐（NNCAs）的一锅开环聚合反应合成类肽。但是，NNCA的聚合速度可能会非常慢，尤其是对于携带大量N的NNCA-替代组。这阻碍了对具有更多种结构和功能的多肽的探索。因此，迫切需要开发先进的策略，以加速在非活性NNCA上的聚合。据此，我们报道六甲基二硅叠氮化锂/钠/钾（Li / Na / KHMDS）比常用的胺引发剂在NNCA上引发明显更快的聚合反应，尤其是对于具有大的N-取代基的NNCA 。这种快速的NNCA聚合反应将增加多肽的结构多样性，并将其用作多肽的合成模拟物。
• US5166154A
  申请人：——

  公开号：US5166154A

  公开（公告）日：1992-11-24