methyl 2-Benzyl-3-(4-methyl-piperazin-1-ylsulfonyl)propionate | 138742-44-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 2-Benzyl-3-(4-methyl-piperazin-1-ylsulfonyl)propionate
• 英文别名: Methyl 2-Benzyl-3-(1-methyl-piperazin-4-ylsulfonyl)proprionate；methyl 2-Benzyl-3-(1-methyl-piperazin-4-ylsulfonyl)propionate；methyl 2-benzyl-3-(4-methylpiperazin-1-yl)sulfonylpropanoate
• CAS: 138742-44-6
• 化学式: C₁₆H₂₄N₂O₄S
• 分子量: 340.444
• InChiKey: GQJBXQMSGCKAEV-UHFFFAOYSA-N

物化性质

• 沸点：
  478.9±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  75.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-Benzyl-3-(4-methyl-piperazin-1-ylsulfonyl)propionate 在 水 作用下， 以 丙酮 为溶剂， 反应 72.0h， 生成 (2S)-N-[1-[[(2S,3R,4S)-1-环己基-3,4-二羟基-6-甲基庚烷-2-基]氨基]-1-氧代-3-(1,3-噻唑-4-基)丙-2-基]-2-[(4-甲基哌嗪-1-基)磺酰基甲基]-3-苯丙酰胺
  参考文献：
  名称：

  Enzyme-catalyzed synthesis of optically Pure β-sulfonamidopropionic acids. Useful starting materials for P-3 site modified renin inhibitors.

  摘要：

  The novel and efficient preparation of several racemic beta-sulfonamidopropionate esters is described. Treatment of the racemic esters with Chymotrypsin or Subtilisin Carlsberg (purified or detergent grade) provided the corresponding (S)-carboxylic acids in 60-90% yield. These acids (75 to >98 % e.e.) are useful starting materials for the synthesis of P-3 site modified renin inhibitors.

  DOI：

  10.1016/0040-4039(93)85095-e
• 作为产物：
  描述：

  (Z)-methyl 2-(bromomethyl)-3-phenylacrylate 在 镍 五氯化磷 、 氢气 、 sodium sulfite 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 生成 methyl 2-Benzyl-3-(4-methyl-piperazin-1-ylsulfonyl)propionate
  参考文献：
  名称：

  Enzyme-catalyzed synthesis of optically Pure β-sulfonamidopropionic acids. Useful starting materials for P-3 site modified renin inhibitors.

  摘要：

  The novel and efficient preparation of several racemic beta-sulfonamidopropionate esters is described. Treatment of the racemic esters with Chymotrypsin or Subtilisin Carlsberg (purified or detergent grade) provided the corresponding (S)-carboxylic acids in 60-90% yield. These acids (75 to >98 % e.e.) are useful starting materials for the synthesis of P-3 site modified renin inhibitors.

  DOI：

  10.1016/0040-4039(93)85095-e

文献信息

• Encapsulated renin inhibitor composition
  申请人：Abbott Laboratories

  公开号：US05178877A1

  公开（公告）日：1993-01-12

  A pharmaceutical composition comprising a solution of a tenin inhibitor of the formula: ##STR1## wherein R.sub.1 is 4-piperazinyl, 1-methyl-4-piperazinyl, 1-methyl-1-oxo-4-piperazinyl, 2-oxo-4-piperazinyl, 4-morpholinyl, 4-thiomorpholinyl or 1-methyl-4-homopiperazinyl; R.sub.2 is benzyl, p-methoxybenzyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthylmethyl; R.sub.3 is 4-thiazolyl, 2-amino-4-thiazolyl, 2-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl, 1-imidazolyl, n-propyl, isopropyl, CH.sub.3 S-- or CH.sub.3 SCH.sub.2 --; R.sub.4 is loweralkyl or cyclopropyl; R.sub.5 is hydrogen or loweralkyl; and X is CH.sub.2 or NH; or a pharmaceutically acceptable salt, ester or prodrug thereof in a pharmaceutically acceptable solvent, said solution being encapsulated in a soft elastic gelatin capsule.

  一种药物组合物，包括式子为：##STR1##的一种腺苷酸酶抑制剂的溶液，其中R.sub.1为4-哌嗪基，1-甲基-4-哌嗪基，1-甲基-1-氧代-4-哌嗪基，2-氧代-4-哌嗪基，4-吗啉基，4-硫代吗啉基或1-甲基-4-同型哌嗪基；R.sub.2为苯甲基，对甲氧基苯甲基，2-苯乙基，1-萘甲基或2-萘甲基；R.sub.3为4-噻唑基，2-氨基-4-噻唑基，2-噻唑基，5-噻唑基，1-吡唑基，3-吡唑基，1-咪唑基，正丙基，异丙基，CH.sub.3S-或CH.sub.3SCH.sub.2-；R.sub.4为低碳基或环丙基；R.sub.5为氢或低碳基；X为CH.sub.2或NH；或其药学上可接受的盐、酯或前药，溶于药学上可接受的溶剂中，该溶液被封装在柔软的弹性明胶胶囊中。
• Method for treating renal disease
  申请人：Abbott Laboratories

  公开号：US05182266A1

  公开（公告）日：1993-01-26

  The present invention relates to the use of renin inhibitors and to renin inhibitor compositions for prevention, treatment, inhibition or reversal of renal dysfunction or disease, especially renal failure.

  本发明涉及使用肾素抑制剂和肾素抑制剂组合物预防、治疗、抑制或逆转肾功能障碍或疾病，特别是肾衰竭。
• Process for the preparation of a renin inhibiting compound
  申请人：Abbott Laboratories

  公开号：US05275950A1

  公开（公告）日：1994-01-04

  Intermediates and a process for their preparation are disclosed which are useful for the preparation of a renin inhibiting compound of the formula: ##STR1## wherein R is a nitrogen-containing heterocycle which is bonded via a nitrogen atom to the sulfonyl group, R.sub.6 is hydrogen, alkoxy, halogen or loweralkyl, R.sub.7 is loweralkyl having 2 to 7 carbon atoms, and R.sub.8 is loweralkyl, cycloalkyl, or aryl or a pharmaceutically acceptable acid addition salt thereof.

  本发明公开了一种中间体及其制备方法，可用于制备一种抑制肾素的化合物，其化学式为：##STR1## 其中R是通过氮原子与磺酰基结合的含氮杂环，R.sub.6是氢、烷氧基、卤素或低烷基，R.sub.7是具有2至7个碳原子的低烷基，R.sub.8是低烷基、环烷基或芳基，或其药学上可接受的酸加成盐。
• Renin inhibitors
  申请人：Abbott Laboratories

  公开号：US05284849A1

  公开（公告）日：1994-02-08

  A renin inhibiting compound of the formula: ##STR1## wherein R.sub.1 is 4-piperazinyl, 1-methyl-4-piperazinyl, 1-methyl-1-oxo-4-piperazinyl, 2-oxo-4-piperazinyl, 4-morpholinyl, 4-thiomorpholinyl or 1-methyl-4-homopiperazinyl; R.sub.2 is benzyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthylmethyl; R.sub.3 is 4-thiazolyl, 2-amino-4-thiazolyl, 2-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl, 1-imidazolyl, n-propyl, isopropyl, CH.sub.3 S--, or CH.sub.3 SCH.sub.2 --; R.sub.4 is isobutyl or cyclopropyl; R.sub.5 is hydrogen or loweralkyl; and X is CH.sub.2 or NH; or a pharmaceutically acceptable salt, ester or prodrug thereof; with the proviso that when X is NH and R.sub.3 is 2-amino-4-thiazolyl, then R.sub.4 is cyclopropyl.

  一种抑制肾素的化合物，其化学式为：##STR1## 其中R.sub.1为4-哌嗪基，1-甲基-4-哌嗪基，1-甲基-1-氧代-4-哌嗪基，2-氧代-4-哌嗪基，4-吗啉基，4-硫代吗啉基或1-甲基-4-杂环戊二氮基；R.sub.2为苄基，2-苯乙基，1-萘甲基或2-萘甲基；R.sub.3为4-噻唑基，2-氨基-4-噻唑基，2-噻唑基，5-噻唑基，1-吡唑基，3-吡唑基，1-咪唑基，正丙基，异丙基，CH.sub.3 S--或CH.sub.3 SCH.sub.2 --；R.sub.4为异丁基或环丙基；R.sub.5为氢或低碳基；X为CH.sub.2或NH；或其药学上可接受的盐，酯或前药；但是当X为NH且R.sub.3为2-氨基-4-噻唑基时，R.sub.4为环丙基。
• Pharmaceutical composition
  申请人：Abbott Laboratories

  公开号：US05523289A1

  公开（公告）日：1996-06-04

  A pharmaceutical tablet composition comprising a compound of the formula (II): ##STR1## wherein R.sub.1 is 4-piperazinyl, 1-methyl-4-piperazinyl, 1-methyl-1-oxo-4-piperazinyl, 2-oxo-4-piperazinyl, 4-morpholinyl, 4-thiomorpholinyl or 1-methyl-4-homopiperazinyl; R.sub.2 is benzyl, p-methoxybenzyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthylmethyl; R.sub.3 is 4-thiazolyl, 2-amino-4-thiazolyl, 2-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl, 1-imidazolyl, n-propyl, isopropyl, CH.sub.3 S-- or CH.sub.3 SCH.sub.2 --; R.sub.4 is loweralkyl or cyclopropyl; R.sub.5 is hydrogen or loweralkyl; and X is CH.sub.2 or NH; or a pharmaceutically acceptable salt, ester or prodrug thereof, and a pharmaceutically acceptable organic polycarboxylic acid. In addition, the tablet composition can further comprise one or more pharmaceutically acceptable non-ionic surfactants.

  一种制药片剂组合物，包括式（II）的化合物：##STR1## 其中R.sub.1为4-哌嗪基，1-甲基-4-哌嗪基，1-甲基-1-氧代-4-哌嗪基，2-氧代-4-哌嗪基，4-吗啉基，4-硫代吗啉基或1-甲基-4-同型哌嗪基；R.sub.2为苄基，对甲氧基苄基，2-苯乙基，1-萘甲基或2-萘甲基；R.sub.3为4-噻唑基，2-氨基-4-噻唑基，2-噻唑基，5-噻唑基，1-吡唑基，3-吡唑基，1-咪唑基，正丙基，异丙基，CH.sub.3S-或CH.sub.3SCH.sub.2-；R.sub.4为低碳基或环丙基；R.sub.5为氢或低碳基；X为CH.sub.2或NH；或其药学上可接受的盐、酯或前药，以及药学上可接受的有机聚羧酸。此外，该片剂组合物还可以进一步包括一种或多种药学上可接受的非离子表面活性剂。