Tert-butyl 4-(2-methylpropyl)-3-oxopiperazine-1-carboxylate | 1042904-02-8

• 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 4-(2-methylpropyl)-3-oxopiperazine-1-carboxylate
• CAS: 1042904-02-8
• 化学式: C₁₃H₂₄N₂O₃
• 分子量: 256.345
• InChiKey: NWKRJPKHCYMRQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-(2-methylpropyl)-3-oxopiperazine-1-carboxylate 在 氢气 、 palladium(II) hydroxide 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands

  摘要：

  We report the design and synthesis of a series of BACE1 inhibitors incorporating mono- and bicyclic 6 substituted 2-oxopiperazines as novel P1' and P2' ligands and isophthalamide derivative as P2-P3 ligands. Among mono-substituted 2-oxopiperazines, inhibitor 5a with N-benzyl-2-oxopiperazine and isophthalamide showed potent BACE1 inhibitory activity (K-i = 2 nM). Inhibitor 5g, with N-benzyl-2-oxopiperazine and substituted indole-derived P2-ligand showed a reduction in potency. The X-ray crystal structure of 5g-bound BACE1 was determined and used to design a set of disubstituted 2-oxopiperazines and bicyclic derivatives that were subsequently investigated. Inhibitor 6j with an oxazolidinone derivative showed a BACE1 inhibitory activity of 23 nM and cellular EC50 of 80 nM. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.04.011
• 作为产物：
  描述：

  3-氧代-1-哌嗪羧酸叔丁酯 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydride 作用下， 生成 Tert-butyl 4-(2-methylpropyl)-3-oxopiperazine-1-carboxylate
  参考文献：
  名称：

  Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors

  摘要：

  Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.

  DOI：

  10.1016/j.bmcl.2008.04.050

文献信息

• NEW COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS RELATING THERETO
  申请人：DYCK Brian

  公开号：US20110166116A1

  公开（公告）日：2011-07-07

  New compounds are disclosed which have utility in the treatment of a variety of metabolic related conditions in a patient. The compounds of this invention have the structure (I): wherein R 1 , R 2 , R 3 , n, p, q, and Ar are as defined herein, including stereoisomers, and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising a compound of this invention, as well as methods relating to the use thereof in a patient in need thereof.

  本发明披露了一种新化合物，其在治疗患者的各种代谢相关疾病方面具有用途。本发明的化合物具有结构（I）：其中R1、R2、R3、n、p、q和Ar的定义如本文所述，包括立体异构体和药物可接受的盐。本发明还披露了包括本发明化合物的制药组合物，以及与在需要时使用该化合物的相关方法。
• 2-AMINOPYRIDINE ANALOGS AS GLUCOKINASE ACTIVATORS
  申请人：Array BioPharma Inc.

  公开号：US20130065901A1

  公开（公告）日：2013-03-14

  Provided are compounds that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.

  提供了一些化合物，它们在治疗和/或预防由葡萄糖激酶活性不足引起的疾病中非常有用，例如糖尿病。此外，还提供了治疗或预防由葡萄糖激酶活性不足或可以通过激活葡萄糖激酶来治疗的疾病和障碍的方法。
• COMPOUNDS FOR TREATMENT OF ALZHEIMER'S DISEASE
  申请人：Purdue Research Foundation

  公开号：EP2349308A1

  公开（公告）日：2011-08-03
• US8293729B2
  申请人：——

  公开号：US8293729B2

  公开（公告）日：2012-10-23
• US8703947B2
  申请人：——

  公开号：US8703947B2

  公开（公告）日：2014-04-22