(3S)-trans-hexahydro-2-oxo-3-phthalimido-7-(2-propenyl)-1H-azepine-1-acetic acid methyl ester | 155013-05-1

• 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: (3S)-trans-hexahydro-2-oxo-3-phthalimido-7-(2-propenyl)-1H-azepine-1-acetic acid methyl ester
• 英文别名: (3S-trans)-Hexahydro-3-phthalimido-2-oxo-7-(2-propenyl)-1H-azepine-1-acetic acid, methyl ester；methyl 2-[(3S,7R)-3-(1,3-dioxoisoindol-2-yl)-2-oxo-7-prop-2-enylazepan-1-yl]acetate
• CAS: 155013-05-1
• 化学式: C₂₀H₂₂N₂O₅
• 分子量: 370.405
• InChiKey: GCRAITLLNPNQGQ-BBRMVZONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S)-trans-hexahydro-2-oxo-3-phthalimido-7-(2-propenyl)-1H-azepine-1-acetic acid methyl ester 在 sodium hydroxide 、 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 一水合肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 73.0h， 生成 [3S-[3α(R*),7β]]-hexahydro-3-[(2-mercapto-1-oxo-3-phenylpropyl)amino]-2-oxo-7-(2-propenyl)-1H-azepine-1-acetic acid
  参考文献：
  名称：

  双重金属蛋白酶抑制剂。6.将双环和取代的单环a庚酮作为二肽替代物掺入血管紧张素转化酶/中性内肽酶抑制剂中。

  摘要：

  一系列取代的单环和双环a庚酮以巯基乙酰基二肽的二肽替代物形式并入，希望产生一种能有效抑制血管紧张素转化酶（ACE）和中性内肽酶（NEP）的化合物。这些化合物中有许多显示出对两种酶的出色效力。两种最有效的化合物，单环a庚酮2n和双环a庚酮3q，在体外和体内均显示出比ACE和NEP更高的活性。

  DOI：

  10.1021/jm950677a
• 作为产物：
  描述：

  L-6-羟基正亮氨酸 在 N-甲基吗啉 、 草酰氯 、 溴化锡 、 sodium carbonate 、 二甲基亚砜 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.92h， 生成 (3S)-trans-hexahydro-2-oxo-3-phthalimido-7-(2-propenyl)-1H-azepine-1-acetic acid methyl ester
  参考文献：
  名称：

  Peptidomimetic Synthesis: A Novel, Highly Stereoselective Route to Substituted Freidinger Lactams

  摘要：

  New methodology for the synthesis of substituted seven-membered lactams 3 has been developed. This method allows for the stereoselective introduction of substituents at the C-7 position of the azepinone ring as well as a to the acetic acid side chain. Dehydrative cyclization of dipeptidyl aldehydes 11 affords the corresponding bicyclic fused lactams 12 in good yield and high stereoselectivity. Lewis acid catalyzed reduction of 12 with triethylsilane provides azepinones 16 in homochiral form. Introduction of substituents at the C-7 position was effected by treatment of 12 with various alkyl nucleophiles. The resulting azepinones may be viewed as conformationally restricted dipeptidomimetic surrogates.

  DOI：

  10.1021/ja00085a014

文献信息

• Substituted azepinone dual inhibitors of angiotensin converting enzyme
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05552397A1

  公开（公告）日：1996-09-03

  Compounds of the formula ##STR1## are disclosed as possessing inhibitory activity against angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) and thus being useful as cardiovascular agents. Processes for preparing these compounds are also disclosed.

  公式##STR1##的化合物被披露具有抑制血管紧张素转换酶（ACE）和中性内肽酶（NEP）活性的特性，因此可用作心血管药物。同时也披露了制备这些化合物的方法。
• Peptidomimetic Synthesis: A Novel, Highly Stereoselective Route to Substituted Freidinger Lactams
  作者：Jeffrey A. Robl、Maria P. Cimarusti、Ligaya M. Simpkins、Harold N. Weller、Yolanda Y. Pan、Mary Malley、John D. DiMarco

  DOI：10.1021/ja00085a014

  日期：1994.3

  New methodology for the synthesis of substituted seven-membered lactams 3 has been developed. This method allows for the stereoselective introduction of substituents at the C-7 position of the azepinone ring as well as a to the acetic acid side chain. Dehydrative cyclization of dipeptidyl aldehydes 11 affords the corresponding bicyclic fused lactams 12 in good yield and high stereoselectivity. Lewis acid catalyzed reduction of 12 with triethylsilane provides azepinones 16 in homochiral form. Introduction of substituents at the C-7 position was effected by treatment of 12 with various alkyl nucleophiles. The resulting azepinones may be viewed as conformationally restricted dipeptidomimetic surrogates.
• Dual Metalloprotease Inhibitors. 6. Incorporation of Bicyclic and Substituted Monocyclic Azepinones as Dipeptide Surrogates in Angiotensin-Converting Enzyme/Neutral Endopeptidase Inhibitors
  作者：Jeffrey A. Robl、Maria P. Cimarusti、Ligaya M. Simpkins、Baerbel Brown、Denis E. Ryono、J. Eileen Bird、Magdi M. Asaad、Thomas R. Schaeffer、Nick C. Trippodo

  DOI：10.1021/jm950677a

  日期：1996.1.1

  series of substituted monocyclic and bicyclic azepinones were incorporated as dipeptide surrogates in mercaptoacetyl dipeptides with the desire to generate a single compound which would potently inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). Many of these compounds displayed excellent potency against both enzymes. Two of the most potent compounds, monocyclic azepinone

  一系列取代的单环和双环a庚酮以巯基乙酰基二肽的二肽替代物形式并入，希望产生一种能有效抑制血管紧张素转化酶（ACE）和中性内肽酶（NEP）的化合物。这些化合物中有许多显示出对两种酶的出色效力。两种最有效的化合物，单环a庚酮2n和双环a庚酮3q，在体外和体内均显示出比ACE和NEP更高的活性。