4-(2,3-bis(tert-butoxycarbonyl)guanidino)butanoic acid

• 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: 4-(2,3-bis(tert-butoxycarbonyl)guanidino)butanoic acid
• 英文别名: 4-[(2-methylpropan-2-yl)oxycarbonyl-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]amino]butanoic acid
• 化学式: C₁₅H₂₇N₃O₆
• 分子量: 345.396
• InChiKey: ASGALMLKLZPPTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(2,3-bis(tert-butoxycarbonyl)guanidino)butanoic acid 、 1-苄基-4-(苯基氨基)哌啶-4-甲胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以77%的产率得到tert-butyl 1-(1-benzyl-4-(phenylamino)piperidin-4-yl)-12,12-dimethyl-3,10-dioxo-11-oxa-2,7,9-triazatridecan-8-ylidenecarbamate
  参考文献：
  名称：

  Nonpeptide Small Molecule Agonist and Antagonist Original Leads for Neuropeptide FF1 and FF2 Receptors

  摘要：

  Neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R), and their endogenous ligand NPFF, are one of only several systems responsible for mediating opioid-induced hyperalgesia, tolerance, and dependence. Currently, no small molecules displaying good affinity or selectivity for either subtype have been reported, to decipher the role of NPFF2-R as it relates to opioid-mediated analgesia, for further exploration of NPFF1-R, or for medication development for either subtype. We report the first nonpeptide small molecule scaffold for NPFF1,2-R, the guanidino-piperidines, and SAR studies resulting in the discovery of a NPFF1 agonist (7b, K-i = 487 +/- 117 nM), a NPFF1 antagonist (46, K-i = 81 +/- 17 nM), and a NPFF2 partial antagonist (53a, K-i = 30 +/- 5 nM), which serve as leads for the development of pharmacological probes and potential therapeutic agents. Testing of 46 alone was without effect in the mouse 48 degrees C warm-water tail-withdrawal test, but pretreatment with 46 prevented NPFF-induced hyperalgesia.

  DOI：

  10.1021/jm500989n
• 作为产物：
  描述：

  N,N'-bis-Boc-S-methyl-isothiourea 、 4-氨基丁酸 在 三乙胺 、 mercury dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 4-(2,3-bis(tert-butoxycarbonyl)guanidino)butanoic acid
  参考文献：
  名称：

  Nonpeptide Small Molecule Agonist and Antagonist Original Leads for Neuropeptide FF1 and FF2 Receptors

  摘要：

  Neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R), and their endogenous ligand NPFF, are one of only several systems responsible for mediating opioid-induced hyperalgesia, tolerance, and dependence. Currently, no small molecules displaying good affinity or selectivity for either subtype have been reported, to decipher the role of NPFF2-R as it relates to opioid-mediated analgesia, for further exploration of NPFF1-R, or for medication development for either subtype. We report the first nonpeptide small molecule scaffold for NPFF1,2-R, the guanidino-piperidines, and SAR studies resulting in the discovery of a NPFF1 agonist (7b, K-i = 487 +/- 117 nM), a NPFF1 antagonist (46, K-i = 81 +/- 17 nM), and a NPFF2 partial antagonist (53a, K-i = 30 +/- 5 nM), which serve as leads for the development of pharmacological probes and potential therapeutic agents. Testing of 46 alone was without effect in the mouse 48 degrees C warm-water tail-withdrawal test, but pretreatment with 46 prevented NPFF-induced hyperalgesia.

  DOI：

  10.1021/jm500989n

文献信息

• [EN] CATIONIC LIPIDS<br/>[FR] LIPIDES CATIONIQUES
  申请人：UNIV EDINBURGH

  公开号：WO2009050483A1

  公开（公告）日：2009-04-23

  This invention relates to cationic lipids. More particularly the invention relates to biodegradable cationic lipids having a plurality of cationic headgroups and one or more lipophilic tail groups. The lipids are of utility in various applications, and in particular in permitting transfection of molecules, and in particular DNA and RNA, into cells. As such the lipids have specific utility in the field of gene therapy as well as other applications such as delivery of small molecules into cells, detergents, and metal ion complexation for medical or industrial applications.

  这项发明涉及阳离子脂质。更具体地，该发明涉及具有多个阳离子头基和一个或多个亲脂尾基的可生物降解阳离子脂质。这些脂质在各种应用中具有实用性，特别是在允许分子转染，特别是DNA和RNA，进入细胞方面。因此，这些脂质在基因治疗领域以及其他应用中具有特定的实用性，如将小分子输送到细胞中、洗涤剂以及医疗或工业应用中的金属离子络合。
• PEPTIDE DERIVATIVES AND MEDICINAL COMPOSITIONS
  申请人：Nippon Shinyaku Co., Ltd.

  公开号：EP1275657A1

  公开（公告）日：2003-01-15

  An object of the present invention is to provide a novel nociceptin receptor agonist. The present invention relates to a peptide derivative represented by the following general formula (1):    (in which A represents alkylene, -(CH2)nCO- or a group represented by the following formula (2) or (3): wherein n represents an integer of 1 to 8; X and Y are same or different and each represents -CONH- or -CH2NH-; R1, R2 and R3 are same or different and each represents alkyl, aryl or heteroaryl; Z represents -CON(R4)R5 or -CH2N(R4)R5; and R4 and R5 are same or different and each represents hydrogen, alkyl, aryl or heteroaryl) or a pharmaceutically acceptable salt thereof. A pharmaceutical composition according to the present invention is useful as a nociceptin receptor agonist.

  本发明的目的是提供一种新型痛觉素受体激动剂。 本发明涉及一种由下式通式（1）代表的肽衍生物： (其中 A 代表亚烷基、-(CH2)nCO- 或下式(2)或(3)所代表的基团： 其中 n 代表 1 至 8 的整数；X 和 Y 相同或不同，各自代表-CONH-或-CH2NH-；R1、R2 和 R3 相同或不同，各自代表烷基、芳基或杂芳基；Z 代表-CON(R4)R5 或-CH2N(R4)R5；R4 和 R5 相同或不同，各自代表氢、烷基、芳基或杂芳基）或其药学上可接受的盐。 根据本发明的药物组合物可用作痛觉素受体激动剂。
• CATIONIC LIPIDS
  申请人：The University Court Of The University of Edinburgh

  公开号：EP2212279A1

  公开（公告）日：2010-08-04
• US5340809A
  申请人：——

  公开号：US5340809A

  公开（公告）日：1994-08-23
• US7163921B1
  申请人：——

  公开号：US7163921B1

  公开（公告）日：2007-01-16