(3S,7S,11S)-1-aza-3-benzyloxycarbonylamino-11-methoxycarbonyl-2-oxo-6-thiabicyclo[5.4.0]undecane | 167305-43-3

• 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,7S,11S)-1-aza-3-benzyloxycarbonylamino-11-methoxycarbonyl-2-oxo-6-thiabicyclo[5.4.0]undecane
• 英文别名: [4S-(4α,7α,10aβ)]-Octahydro-5-oxo-4-[[(phenylmethoxy)carbonyl]amino]-7H-pyrido-[2,1-b] [1,3]thiazepine-7-carboxylic methyl ester；[4S-(4α,7α,10aβ)]-Octahydro-4-[[(phenylmethoxy)carbonyl]amino]-5-oxo-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid, methyl ester；methyl (4S,7S,10aS)-5-oxo-4-(phenylmethoxycarbonylamino)-2,3,4,7,8,9,10,10a-octahydropyrido[2,1-b][1,3]thiazepine-7-carboxylate
• CAS: 167305-43-3
• 化学式: C₁₉H₂₄N₂O₅S
• 分子量: 392.476
• InChiKey: LMNAYDQXDAQHFT-JYJNAYRXSA-N

物化性质

• 沸点：
  598.5±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,7S,11S)-1-aza-3-benzyloxycarbonylamino-11-methoxycarbonyl-2-oxo-6-thiabicyclo[5.4.0]undecane 在 碘代三甲硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以92%的产率得到[4S-(4α,7α,10aβ)]-4-amino-octahydro-5-oxo-7H-pyrido[2,1-b] [1,3]thiazepine-7-carboxylic acid, methyl ester
  参考文献：
  名称：

  Dual Metalloprotease Inhibitors:  Mercaptoacetyl-Based Fused Heterocyclic Dipeptide Mimetics as Inhibitors of Angiotensin-Converting Enzyme and Neutral Endopeptidase

  摘要：

  A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiated urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency and duration of action, compound 1a (BMS-186716) was advanced into clinical development for the treatment of hypertension and congestive heart failure.

  DOI：

  10.1021/jm970041e
• 作为产物：
  描述：

  N-Benzyloxycarbonyl-D,L-homocystein-thiolacton 在 N-甲基吗啉 、 甲醇 、 氢氧化钾 、 草酰氯 、 sodium methylate 、 1-羟基苯并三唑 、 二甲基亚砜 、 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 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 41.67h， 生成 (3S,7S,11S)-1-aza-3-benzyloxycarbonylamino-11-methoxycarbonyl-2-oxo-6-thiabicyclo[5.4.0]undecane
  参考文献：
  名称：

  Dual Metalloprotease Inhibitors:  Mercaptoacetyl-Based Fused Heterocyclic Dipeptide Mimetics as Inhibitors of Angiotensin-Converting Enzyme and Neutral Endopeptidase

  摘要：

  A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiated urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency and duration of action, compound 1a (BMS-186716) was advanced into clinical development for the treatment of hypertension and congestive heart failure.

  DOI：

  10.1021/jm970041e

文献信息

• Preparation of
  申请人：Bristol-Myers Squibb Co.

  公开号：US06162913A1

  公开（公告）日：2000-12-19

  N-protected-L-homocysteine disulfide of the formula ##STR1## or an activated form thereof is reacted with (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester to give the disulfide intermediate of the formula ##STR2## Cleavage of the disulfide bond followed by acid catalyzed cyclization produces the N-protected lactam of formula III which is useful for preparing the pharmaceutically active compound omapatrilat.

  N-保护的-L-同型半胱氨酸二硫化物的结构式为##STR1##或其活化形式与(S)-2-氨基-6,6-二甲氧基己酸甲酯反应，得到结构式为##STR2##的二硫化物中间体。断裂二硫键后，经酸催化环化产生结构式III的N-保护内酰胺，可用于制备药用活性化合物奥马帕曲。
• Highly Efficient Synthesis of Azabicyclo[<i>x</i>.<i>y</i>.0]alkane Amino Acids and Congeners by Means of Rh-Catalyzed Cyclohydrocarbonylation
  作者：Wen-Hua Chiou、Nobihiro Mizutani、Iwao Ojima

  DOI：10.1021/jo061692y

  日期：2007.3.1

  A highly efficient method for the synthesis of 1-azabicyclo[x.y.0]alkane amino acid derivatives and their congeners by means of extremely regioselective cyclohydrocarbonylation (CHC) is described. The CHC reactions are catalyzed by Rh-BIPHEPHOS complex under mild conditions. These CHC reaction processes involve (i) an extremely linear-selective hydroformylation of the terminal alkene moiety of a dehydrodipeptide

  合成1-氮杂双环[ x的高效方法。ÿ 0.0]烷烃氨基酸衍生物和由极区域选择性cyclohydrocarbonylation（CHC）的装置及其同类物进行说明。在温和条件下，Rh-BIPHEPHOS络合物催化CHC反应。这些CHC反应过程涉及（i）脱氢二肽底物的末端烯烃部分的极线性选择性加氢甲酰基化;（ii）分子内缩合形成环状N-酰亚胺关键中间体;和（iii）通过分子内亲核加成第二次环化环状N-酰基亚氨基部分的杂原子亲核基团得到相应的1-氮杂双环[ x]。ÿ.0]系统。在大多数情况下，此连续的双环化过程以极高的非对映选择性进行。此方法已成功应用于1-azabicyclo [4.4.0]，-[5.4.0]和-[4.3.0]系统的合成。介绍了反应的机理和观察到的极高非对映选择性的原理。这种Rh催化的CHC方法将用作合成各种构象受限的二肽，拟肽，生物碱和其他具有生物活性的天然或非天然产物的高效且通用的方法。
• J. Med. Chem. 1997, 40, 1570-1577
  作者：

  DOI：——

  日期：——
• US6162913A
  申请人：——

  公开号：US6162913A

  公开（公告）日：2000-12-19
• THE SYNTHESIS OF OMAPATRILAT
  申请人：[en]ENDOTHELIUM SCANNING NANOTECHNOLOGY LIMITED

  公开号：WO2024103123A1

  公开（公告）日：2024-05-23

  Described herein are improved methods of making Compound 1 (4S,7S,10aS)-4-((S)-2- mercapto-3-phenylpropanamido)-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid, or Omapatrilat, and purified Omapatrilat obtained from the improved methods.