(R,S)-5-benzoylamino-4-oxo-6-phenylhexanoic acid methyl ester | 77982-73-1

• 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: (R,S)-5-benzoylamino-4-oxo-6-phenylhexanoic acid methyl ester
• 英文别名: methyl δ-(benzoylamino)-γ-oxobenzenehexanoate；(+/-)-methyl 5-(N-benzoyl)amino-4-oxo-6-phenylhexanoate；methyl 6-phenyl-5-(benzoylamino)-4-oxohexanoate；Methyl 5-benzoylamino-4-oxo-6-phenylhexanoate；Methyl 5-Benzamido-4-oxo-6-phenylhexanoate；Methyl I-(benzoylamino)-I(3)-oxobenzenehexanoate
• CAS: 77982-73-1
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: HYBARONTDNEPOW-UHFFFAOYSA-N

物化性质

• 沸点：
  556.0±45.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R,S)-5-benzoylamino-4-oxo-6-phenylhexanoic acid methyl ester 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 27.0h， 生成 5-氨基-4-氧代-6-苯基己酸甲酯盐酸盐
  参考文献：
  名称：

  Marastoni; Balboni; Salvadori, Arzneimittel-Forschung/Drug Research, 1985, vol. 35, # 11, p. 1630 - 1632

  摘要：

  DOI：
• 作为产物：
  描述：

  4-苄基-2-苯基-2-噁唑啉-5-酮 在 吡啶 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 (R,S)-5-benzoylamino-4-oxo-6-phenylhexanoic acid methyl ester
  参考文献：
  名称：

  Derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline: effect of changes at postions 2 and 5 of the hexanoic acid portion

  摘要：

  Several derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and tested for converting enzyme inhibition activity and blood pressure lowering effects in rats. One compound, 5(S)-benzamido-2(R)-methyl-4-oxo-6-phenylhexanoyl-L-proline (2a), had and I50 against angiotensin converting enzyme of 1.0 x 10(-9) M and is the most potent inhibitor prepared thus far in this class of compounds. Testing of 2a orally at 30 mg/kg for inhibition of the angiotensin I induced blood pressure increase in conscious normotensive rats gave 100% inhibition that required 143 min before the angiotensin I blood pressure response returned to 70% of the pretreatment control response. In the conscious renal hypertensive rat, 2a given orally at a dose of 3 mg/kg caused a lowering of blood pressure that reached its maximum of 40 mmHg 8 h following drug administration.

  DOI：

  10.1021/jm00353a005

文献信息

• Oxoalkanoic acid derivatives as inhibitors of angiotensin converting
  申请人：——

  公开号：US04329473A1

  公开（公告）日：1982-05-11

  This invention relates to novel analogs of proline terminal tripeptides and related compounds and is typified by ##STR1## The compounds are potent inhibitors of angiotensin converting enzyme and as such are useful as antihypertensive agents.

  这项发明涉及脯氨酸末端三肽的新型类似物和相关化合物，其代表性结构如下：##STR1## 这些化合物是抑制血管紧张素转化酶的有效抑制剂，因此可作为降压药物使用。
• Novel synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline and analogs: potent angiotensin converting enzyme inhibitors
  作者：Robert F. Meyer、Ernest D. Nicolaides、Francis G. Tinney、Elizabeth A. Lunney、Ann Holmes、Milton L. Hoefle、Ronald D. Smith、Arnold D. Essenburg、Harvey R. Kaplan、Ronald G. Almquist

  DOI：10.1021/jm00140a010

  日期：1981.8

  in vitro angiotensin converting enzyme (ACE) inhibitory activity of 1 was confirmed. Some of the novel analogues (6, 11, 13, and 17) were also found to be potent inhibitors of ACE in vitro with an IC50 of 1.4-8.8 x 10(-9) M (IC50 for captopril = 0.9 x 10(-8) M). In vivo these compounds (6, 11, 17, and 18) were much less active than captopril, especially by the oral route. Against angiotensin I (AI) challenge

  开发了一种新的合成（S）-1- [5-（苯甲酰氨基）-1,4-二氧代-6-苯基己基] -L-脯氨酸（1）和23种类似物的方法。δ-（酰基氨基）-γ-酮酸中间体是使用3-羰基甲氧基丙酰氯通过改良的Dakin-West反应获得的。L-脯氨酸的酰化和非对映异构体混合物的重结晶在三个反应步骤中得到光学纯的标题化合物。证实了体外血管紧张素转化酶（ACE）的抑制活性为1。还发现一些新型类似物（6、11、13和17）是体外有效的ACE抑制剂，IC50为1.4-8.8 x 10（-9）M（卡托普利的IC50 = 0.9 x 10（- 8）M）。在体内，这些化合物（6、11、17和18）的活性比卡托普利低得多，尤其是通过口服途径。针对血压正常的大鼠的血管紧张素I（AI）攻击，1和6在30 mg / kg口服时产生小于50％的抑制，但是在3 mg / kg iv下产生57至82％的抑制。两种途径的抑制持续不到
• Ketomethylene pseudopeptide analogs of substance P: synthesis and biological activity
  作者：Ariel Ewenson、Ralph Laufer、Michael Chorev、Zvi Selinger、Chaim Gilon

  DOI：10.1021/jm00152a020

  日期：1986.2

  characterized, and tested for their biological activity and inhibitory effect on SP degrading enzymes. Analogue II was a full agonist contracting the isolated guinea pig ileum with a potency of 70% compared to the parent hexapeptide [pGlu6]SP6-11. It was also a potent inhibitor of SP degrading activity in rat diencephalon membranes with a Ki of 20 microM whereas analogue I was a weak inhibitor.

  与P相关的C端的两个假肽类似物[Bz-（RS）Phe8 psi（COCH2）Gly9] SP8-11（I）和[pGlu6，（RS）Phe8 psi（COCH2）Gly9] SP6-11（II）如下制备六肽[pGlu6] SP6-11。伪二肽单元H（RS）Phe psi（COCH2）GlyOH是通过Bz-Phe-OH与单甲基琥珀酰氯之间的修饰的Dakin-West反应合成的。然后通过使用各种偶联方法将Nα-保护的假肽单元掺入适当的肽中。纯化，表征并测试了两种假肽类似物的生物活性以及对SP降解酶的抑制作用。与亲本六肽[pGlu6] SP6-11相比，类似物II是完全的激动剂，可收缩分离的豚鼠回肠，效力为70％。
• Nickel‐Catalyzed Enantioselective Decarboxylative Acylation: Rapid, Modular Access to α‐Amino Ketones**
  作者：Yang Gao、Phil S. Baran

  DOI：10.1002/anie.202315203

  日期：2023.12.11

  A new approach to the enantiocontrolled synthesis of α-amino ketone derivatives is disclosed by employing a nickel-catalyzed decarboxylative acylation strategy. Starting from readily available acyl chlorides and α-amino acids-derived redox-active esters, the reaction exhibits broad substrate scope, easy scalability, and is applied to dramatically simplify the synthesis of several known structures.

  通过采用镍催化的脱羧酰化策略，揭示了一种对映体控制合成 α-氨基酮衍生物的新方法。该反应从现成的酰氯和 α-氨基酸衍生的氧化还原活性酯开始，表现出广泛的底物范围、易于扩展，并可用于显著简化几种已知结构的合成。
• Chain extension of amino acid skeletons: preparation of ketomethylene isosteres
  作者：Cory R Theberge、Charles K Zercher

  DOI：10.1016/s0040-4020(03)00052-8

  日期：2003.2

  Ketomethylene isosteric replacements for peptide bonds were generated through a zinc carbenoid-mediated chain extension reaction in which a variety of amino acid-derived beta-keto esters are converted to gamma-keto esters in a single step. The reaction tolerates a variety of protecting groups and amino acid side chains with no epimerization of the amino acid stereocenter. (C) 2003 Elsevier Science Ltd. All rights reserved.