benzyl 4-(2-oxo-1,3-oxazolidin-3-yl)piperidine-1-carboxylate | 164518-98-3

• 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: benzyl 4-(2-oxo-1,3-oxazolidin-3-yl)piperidine-1-carboxylate
• 英文别名: 1-benzyloxycarbonyl-4-(2-oxo-1,3-oxazolidin-3-yl)piperidine；1-benzyloxycarbonyl-4-(oxazolidin-2-on-3-yl)piperidine
• CAS: 164518-98-3
• 化学式: C₁₆H₂₀N₂O₄
• 分子量: 304.346
• InChiKey: NVTWNUUZSSQGLJ-UHFFFAOYSA-N

物化性质

• 沸点：
  520.9±50.0 °C(Predicted)
• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl 4-(2-oxo-1,3-oxazolidin-3-yl)piperidine-1-carboxylate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 3-(哌啶-4-基)恶唑烷-2-酮
  参考文献：
  名称：

  Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure–Activity relationships for 1-[N-(Methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes

  摘要：

  (2S)-2-(3-氯苯基)-1-[N-(甲基)-N-(苯磺酰基)氨基]-4-[螺环(2,3-二氢苯并噻吩-3,4'-哌啶-1'-基)]丁烷 S-氧化物 (lb) 已被鉴定为一种强效的 CCR5 拮抗剂，其 IC50 = 10 nM。在此，描述了非螺环哌啶的结构-活性关系研究，这些研究导致了发现 4-(N-(烷基)-N-(苯甲酰氧基)氨基)哌啶衍生物 (3-5) 作为强效的 CCR5 拮抗剂。(C) 2001 Elsevier Science Ltd. 保留所有权利。

  DOI：

  10.1016/s0960-894x(01)00492-9
• 作为产物：
  描述：

  4-异硫氰四羟基-1(2H)-吡啶甲酸苄酯 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl 4-(2-oxo-1,3-oxazolidin-3-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure–Activity relationships for 1-[N-(Methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes

  摘要：

  (2S)-2-(3-氯苯基)-1-[N-(甲基)-N-(苯磺酰基)氨基]-4-[螺环(2,3-二氢苯并噻吩-3,4'-哌啶-1'-基)]丁烷 S-氧化物 (lb) 已被鉴定为一种强效的 CCR5 拮抗剂，其 IC50 = 10 nM。在此，描述了非螺环哌啶的结构-活性关系研究，这些研究导致了发现 4-(N-(烷基)-N-(苯甲酰氧基)氨基)哌啶衍生物 (3-5) 作为强效的 CCR5 拮抗剂。(C) 2001 Elsevier Science Ltd. 保留所有权利。

  DOI：

  10.1016/s0960-894x(01)00492-9

文献信息

• [EN] HETEROCYCLES USEFUL AS NEUROKININ ANTAGONISTS<br/>[FR] HETEROCYCLES APTES A ETRE UTILISES COMME ANTAGONISTES DE LA NEUROKININE
  申请人：ZENECA LIMITED

  公开号：WO1995005377A1

  公开（公告）日：1995-02-23

  (EN) Compounds of formula (I) wherein G, J, L, M, m and D have any of the meanings given in the specification, their N^_-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula (I) and intermediates.(FR) L'invention concerne des composés de la formule (I) dans laquelle G, J, L, M, m et D ont n'importe laquelle des significations données dans le descriptif de l'invention, leurs N^_-oxydes et leurs sels pharmaceutiquement acceptables sont des antagonistes non peptidiques de la neurokinine A et sont utiles dans le traitement de l'asthme, etc. L'invention concerne également des compositions pharmaceutiques, les procédés de préparation des composés de la formule (I) et leurs intermédiaires.

  化合物公式（I）中，G、J、L、M、m和D具有规范中给出的任何含义，它们的N^_-氧化物和药学上可接受的盐是神经激肽A的非肽拮抗剂，可用于治疗哮喘等疾病。还公开了制药组合物、制备化合物公式（I）和中间体的过程。
• Therapeutic heterocycles
  申请人：——

  公开号：US20030187255A1

  公开（公告）日：2003-10-02

  Pharmaceutical compositions containing novel therapeutic heterocycles for use in diseases in which an NK2 receptor is implicated, processes for preparing and methods for using the same.

  含有新型治疗杂环的药物组合物，用于与NK2受体有关的疾病，制备方法和使用方法。
• Therapeutic heterocycles which antagonize neurokinin receptors
  申请人：Zeneca Limited

  公开号：US05567700A1

  公开（公告）日：1996-10-22

  Compounds of formula I ##STR1## wherein G, J, L, M, m and D have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

  式I的化合物 ##STR1## 其中G、J、L、M、m和D具有规范中给出的任何含义，它们的N-氧化物和药学上可接受的盐是神经激肽A的非肽拮抗剂，可用于治疗哮喘等疾病。还披露了制药组合物、制备式I化合物和中间体的过程。
• US6136827
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of a Tetrahydropyrimidin-2(1<i>H</i>)-one Derivative (TAK-442) as a Potent, Selective, and Orally Active Factor Xa Inhibitor
  作者：Takuya Fujimoto、Yasuhiro Imaeda、Noriko Konishi、Katsuhiko Hiroe、Masaki Kawamura、Garret P. Textor、Kathleen Aertgeerts、Keiji Kubo

  DOI：10.1021/jm901699j

  日期：2010.5.13

  Coagulation enzyme factor Xa (FXa) is a particularly promising target for the development of new anticoagulant agents. We previously reported the imidazo[1,5-c]imidazol-3-one derivative 1 as a potent and orally active FXa inhibitor. However, it was found that 1 predominantly undergoes hydrolysis upon incubation with human liver microsomes, and the human specific metabolic pathway made it difficult to predict the human pharmacokinetics. To address this issue, our synthetic efforts were focused on modification of the imidazo[1,5-c]imidazol-3-one moiety of the active metabolite 3a, derived from 1, which resulted in the discovery of the tetrahydropyrimidin-2(1H)-one derivative 5k as a highly potent and selective FXa inhibitor. Compound 5k showed no detectable amide bond cleavage in human liver microsomes, exhibited a good pharmacokinetic profile in monkeys, and had a potent antithrombotic efficacy in a rabbit model without prolongation of bleeding time. Compound 5k is currently under clinical development with the code name TAK-442.