benzyl 9-amino nonanoate | 1394158-05-4

• 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 9-amino nonanoate
• 英文别名: benzyl 10-aminodecanoate
• CAS: 1394158-05-4
• 化学式: C₁₇H₂₇NO₂
• 分子量: 277.407
• InChiKey: LVWWHMQRXJTKCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl 9-amino nonanoate 在 N-甲基吗啉 、 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.25h， 生成 benzyl 10-(10-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)decanamido)decanoate
  参考文献：
  名称：

  细胞周期蛋白依赖性激酶 9 (CDK9) 的双功能降解剂：探索接头长度、特性和选择性蛋白质降解之间的关系

  摘要：

  细胞周期蛋白依赖性激酶 9 (CDK9) 是多种癌症类型（包括急性髓性白血病 (AML)）中有前途的治疗靶点。蛋白质降解剂，也称为蛋白水解靶向嵌合体 (PROTAC)，已成为选择性降解癌症靶标（包括 CDK9）的工具，补充了传统小分子抑制剂的活性。这些化合物通常包含先前报道的抑制剂和已知的 E3 连接酶配体，以诱导泛素化和随后的靶蛋白降解。尽管文献中报道了许多蛋白质降解剂，但有效降解所必需的接头的特性仍然需要特别注意。在这项研究中，开发了一系列蛋白质降解剂，采用经过临床测试的CDK抑制剂 AT7519。本研究的目的是检查连接子组成，特别是链长对效力的影响。除了为各种接头组合物建立活性基线外，还制备了两个不同的同源系列，一个全烷基系列和一个含酰胺系列，证明了这些系列中降解剂效力对接头长度的依赖性以及与预测物理化学的相关性特性。

  DOI：

  10.1016/j.ejmech.2023.115342

文献信息

• [EN] BIFUNCTIONAL DEGRADERS OF HEMATOPOIETIC PROGENITOR KINASE AND THERAPEUTIC USES THEREOF<br/>[FR] AGENTS DE DÉGRADATION BIFONCTIONNELS DE LA KINASE PROGÉNITRICE HÉMATOPOÏÉTIQUE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：NURIX THERAPEUTICS INC

  公开号：WO2021226262A1

  公开（公告）日：2021-11-11

  The present disclosure provides bifunctional compounds as HPK1 degraders via ubiquitin proteosome pathway, and method for treating diseases modulated by HPK1.

  本公开提供了通过泛素蛋白酶体途径作为HPK1降解剂的双功能化合物，以及治疗受HPK1调节的疾病的方法。
• Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR₅)
  作者：Eyup Akgün、Muhammad I. Javed、Mary M. Lunzer、Michael D. Powers、Yuk Y. Sham、Yoshikazu Watanabe、Philip S. Portoghese

  DOI：10.1021/acs.jmedchem.5b01245

  日期：2015.11.12

  Chemokine release promotes cross-talk between opioid and chemokine receptors that in part leads to reduced efficacy of morphine in the treatment of chronic pain. On the basis of the possibility that a MOR-CCR5 heteromer is involved in such cross-talk, we have synthesized bivalent ligands (MCC series) that contain mu opioid agonist and CCR5 antagonist pharmacophores linked through homologous spacers (14-24 atoms). When tested on lipopolysaccharide-inflamed mice, a member of the series (MCC22; 3e) with a 22-atom spacer exhibited profound antinociception (i.t. ED50 = 0.0146 pmol/mouse) that was 2000X greater than morphine. Moreover, MCC22 was similar to 3500X more potent than a mixture of mu agonist and CCR5 antagonist monovalent ligands. These data strongly suggest that MCC22 acts by bridging the protomers of a MOR-CCR5 heteromer having a TM5,6 interface. Molecular simulation studies are consistent with such bridging. This study supports the MOR-CCR5 heteromer as a novel target for the treatment of chronic pain.
• Synthesis of betulinic acid derivatives as entry inhibitors against HIV-1 and bevirimat-resistant HIV-1 variants
  作者：Zhao Dang、Keduo Qian、Phong Ho、Lei Zhu、Kuo-Hsiung Lee、Li Huang、Chin-Ho Chen

  DOI：10.1016/j.bmcl.2012.06.080

  日期：2012.8

  Betulinic acid derivatives modified at the C28 position are HIV-1entry inhibitors such as compound A43D; however, modified at the C3 position instead of C28 give HIV-1 maturation inhibitor such as bevirimat. Bevirimat exhibited promising pharmacokinetic profiles in clinical trials, but its effectiveness was compromised by the high baseline drug resistance of HIV-1 variants with polymorphism in the putative drug binding site. In an effort to determine whether the viruses with bevirimat resistant polymorphism also altered their sensitivities to the betulinic acid derivatives that inhibit HIV-1 entry, a series of new betulinic acid entry inhibitors were synthesized and tested for their activities against HIV-1 NL4-3 and NL4-3 variants resistant to bevirimat. The results show that the bevirimat resistant viruses were approximately 5- to10-fold more sensitive to three new glutamine ester derivatives (13, 15 and 38) and A43D in an HIV-1 multi-cycle replication assay. In contrast, the wild type NL4-3 and the bevirimat resistant variants were equally sensitive to the HIV-1 RT inhibitor AZT. In addition, these three new compounds markedly improved microsomal stability compared to A43D. (c) 2012 Elsevier Ltd. All rights reserved.
• New Betulinic Acid Derivatives for Bevirimat-Resistant Human Immunodeficiency Virus Type-1
  作者：Zhao Dang、Phong Ho、Lei Zhu、Keduo Qian、Kuo-Hsiung Lee、Li Huang、Chin-Ho Chen

  DOI：10.1021/jm3016969

  日期：2013.3.14

  Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with HIV-1 Gag-SP1 processing at a late stage of viral maturation. However, clinical trials of 1 have revealed a high baseline drug resistance that is attributed to naturally occurring polymorphisms in HIV-1 Gag. To overcome the drug resistance, 28 new derivatives of 1 were synthesized and tested against compound 1-resistant (BVM-R) HIV-1 variants. Among them, compound 6 exhibited much improved activity against several HIV-1 strains carrying BVM-R polymorphisms. Compound 6 was at least 20-fold more potent than 1 against the replication of NL4-3/V370A, which carries the most prevalent clinical BVM-R polymorphism in HIV-1 Gag-SP1. Thus, compound 6 merits further development as a potential anti-AIDS clinical trial candidate.