tert-butyl ((S)-1-((S)-1-(4-methylbenzyl)-5-oxopyrrolidine-2-carbonyl)piperidin-3-yl)methylcarbamate | 1391739-80-2

• 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: tert-butyl ((S)-1-((S)-1-(4-methylbenzyl)-5-oxopyrrolidine-2-carbonyl)piperidin-3-yl)methylcarbamate
• 英文别名: tert-butyl N-(((S)-1-(4-methylbenzyl)-5-oxopyrrolidine-2-carbonyl)piperidin-3-yl)methylcarbamate；tert-butyl (((S)-1-(4-methylbenzyl)-5-oxopyrrolidine-2-carbonyl)piperidin-3-yl)methylcarbamate；S007-867；(2S)-1-(4-methylphenylmethyl)-5-oxo-(3S)-2-{[(3-t-butoxycarbonylaminomethyl)]piperidin-1-ylcarbonyl}pyrrolidine；tert-butyl N-[[(3S)-1-[(2S)-1-[(4-methylphenyl)methyl]-5-oxopyrrolidine-2-carbonyl]piperidin-3-yl]methyl]carbamate
• CAS: 1391739-80-2
• 化学式: C₂₄H₃₅N₃O₄
• 分子量: 429.56
• InChiKey: LTZYXGIVMZPRBX-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl ((S)-1-((S)-1-(4-methylbenzyl)-5-oxopyrrolidine-2-carbonyl)piperidin-3-yl)methylcarbamate 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 8.25h， 生成 benzyl (S)-1-(((S)-1-((S)-1-(4-methylbenzyl)-5-oxopyrrolidine-2-carbonyl)piperidin-3-yl)methylamino)-1-oxo-3-phenylpropan-2-ylcarbamate
  参考文献：
  名称：

  Synthesis and identification of chiral aminomethylpiperidine carboxamides as inhibitor of collagen induced platelet activation

  摘要：

  A series of chiral lactam carboxamides of aminomethylpiperidine were synthesized and investigated for the collagen induced in vitro anti-platelet efficacy and collagen plus epinephrine induced in vivo pulmonary thromboembolism. The compound 31a (30 mu M/kg) displayed a remarkable antithrombotic efficacy (60% protection) which was sustained for more than 24 h and points to its excellent bioavailability. The compounds 31a (IC50 = 6.6 mu M) and 32a (IC50 = 37 mu M), as well as their racemic mixture 28i (IC50 = 16 mu M) significantly inhibited collagen-induced human platelet aggregation in vitro. Compound 34c displayed dual mechanism of action against both collagen (IC50 = 3.3 mu M) and U46619 (IC50 = 2.7 mu M) induced platelet aggregation. The pharmacokinetic study of 31a indicated very faster absorption, prolonged and constant systemic exposure and thereby exhibiting better therapeutic response. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.017
• 作为产物：
  描述：

  L-焦谷氨酸甲酯 在 光气 、 水 、 双(三甲基硅烷基)氨基钾 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 23.75h， 生成 tert-butyl ((S)-1-((S)-1-(4-methylbenzyl)-5-oxopyrrolidine-2-carbonyl)piperidin-3-yl)methylcarbamate
  参考文献：
  名称：

  [EN] CHIRAL 1-(4-METHYLPHENYLMETHYL)-5-OXO-{N-[(3-T-BUTOXYCARBONYL- AMINOMETHYL)]-PIPERIDIN-1-YL}-PYRROLIDINE-2-CARBOXAMIDES AS INHIBITORS OF COLLAGEN INDUCED PLATELET ACTIVATION AND ADHESION
  [FR] 1-(4-MÉTHYLPHÉNYLMÉTHYL)-5-OXO-{N-[(3-T-BUTOXYCARBONYLAMINOMÉTHYL)]-

  摘要：

  手性l-(4-甲基苯甲基)-5-氧-{N-[(3-t-丁氧羰基氨甲基)]-哌啶-1-基}-吡咯烷-2-羧酰胺作为胶原诱导的血小板活化和粘附的抑制剂。本发明提供手性(2S)-l-(4-甲基苯甲基)-5-氧-(3S)-{N-[(3-t-丁氧羰基氨甲基)]-哌啶-1-基}-吡咯烷-2-羧酰胺和(2S)-1-(4-甲基苯甲基)-5-氧-(3R)-{N-[(3-t-丁氧羰基氨甲基)]-哌啶-1-基}-吡咯烷-2-羧酰胺，分别为公式6和7。本发明还涉及使用这些分子作为通过胶原受体介导的胶原诱导的血小板粘附和聚集的抑制剂。本发明提供了一种制备公式6和7的手性羧酰胺的方法，该方法具有避免在N-烷基化过程中α-羧基中发生任何消旋的优点。在低温下使用试剂LiHMDS可提供良好的手性纯度的甲基N-(对甲基苯甲基)吡咯酰胺。

  公开号：

  WO2012104866A1

文献信息

• CHIRAL 1-(4-METHYLPHENYLMETHYL)-5-OXO-{N-[(3-T-BUTOXYCARBONYL-AMINOMETHYL)]-PIPERIDIN-1-YL}-PYRROLIDINE-2-CARBOXAMIDES AS INHIBITORS OF COLLAGEN INDUCED PLATELET ACTIVATION AND ADHESION
  申请人：Council of Scientific & Industrial Research

  公开号：EP2670722B1

  公开（公告）日：2016-10-12
• CHIRAL 1-(4-METHYLPHENYLMETHYL)-5-OXO--PYRROLIDINE-2-CARBOXAMIDES AS INHIBITORS OF COLLAGEN INDUCED PLATELET ACTIVATION AND ADHESION
  申请人：Council of Scientific & Industrial Research

  公开号：US20160143896A1

  公开（公告）日：2016-05-26

  Chiral 1-(4-methylphenylmethyl)-5-oxo-N-[(3-t-butoxycarbonyl-aminomethyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamides as inhibitors of collagen induced platelet activation and adhesion. The present invention provides chiral (2S)-1-(4-methyl-phenylmethyl)-5-oxo-(3S)-N-[(3-t-butoxycarbonyl aminomethyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamide, and (2S)-1-(4-methylphenylmethyl)-5-oxo-(3R)-N-[(3-t-butoxycarbonyl amino methyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamide of formula 6 and 7 respectively. The present invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors. The present invention provides a process for preparation of chiral carboxamides of formula 6 and 7 using the process which has advantage to avoid any racemization at the a-carboxylic center, during N-alkylation. The reagent LiHMDS is used at low temperatures to furnish methyl N-(p-methylphenylmethyl)1pyroglutamate in good chiral purity.
• US9206155B2
  申请人：——

  公开号：US9206155B2

  公开（公告）日：2015-12-08
• US9687480B2
  申请人：——

  公开号：US9687480B2

  公开（公告）日：2017-06-27