N¹-[{(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl}methyl]-N¹-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine | 1380336-17-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N¹-[{(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl}methyl]-N¹-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
• 英文别名: TIQ-15；TIQ15；N1-(((R)-1,2,3,4-tetrahydroisoquinolin-3-yl)methyl)-N1-((S)-5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine；N'-[[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]methyl]-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
• CAS: 1380336-17-3
• 化学式: C₂₃H₃₂N₄
• 分子量: 364.534
• InChiKey: MYCKNKHATQGHEV-YADHBBJMSA-N

物化性质

• 沸点：
  547.2±50.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  54.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-3-甲酰基-3,4-二氢-1H-异喹啉-2-羧酸叔丁酯 在 sodium metabisulfite 、 三乙酰氧基硼氢化钠 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 42.5h， 生成 N¹-[{(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl}methyl]-N¹-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
  参考文献：
  名称：

  Discovery of Tetrahydroisoquinoline-Based CXCR4 Antagonists

  摘要：

  A de novo hit-to-lead effort involving the redesign of benzimidazole-containing antagonists of the CXCR4 receptor resulted in the discovery of a novel series of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogues. In general, this series of compounds show good potencies (3-650 nM) in assays involving CXCR4 function, including both inhibition of attachment of X4 HIV-1(IIIB) virus in MAGI-CCR5/CXCR4 cells and inhibition of calcium release in Chem-1 cells. Series profiling permitted the identification of TIQ(R)-stereoisomer 15 as a potent and selective CXCR4 antagonist lead candidate with a promising in vitro profile. The drug-like properties of 15 were determined in ADME in vitro studies, revealing low metabolic liability potential. Further in vivo evaluations included pharmacokinetic experiments in rats and mice, where 15 was shown to have oral bioavailability (F = 63%) and resulted in the mobilization of white blood cells (WBCs) in a dose-dependent manner.

  DOI：

  10.1021/ml400183q

文献信息

• FUSED AZINES AS CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USES RELATED THERETO
  申请人：Emory University

  公开号：EP3153510A1

  公开（公告）日：2017-04-12

  The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing CXCR4 related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer.

  本公开涉及趋化因子 CXCR4 受体调节剂及其相关用途。在某些实施方案中，本公开涉及包含本文公开的化合物或其药学上可接受的盐或原药的药物组合物。在某些实施方案中，本文公开的组合物用于控制与CXCR4相关的病症，通常是预防或治疗病毒感染如HIV或控制癌症。
• Chemokine CXCR4 receptor modulators and uses related thereto
  申请人：EMORY UNIVERSITY

  公开号：US10016408B2

  公开（公告）日：2018-07-10

  The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing CXCR4 related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer.

  本公开涉及趋化因子 CXCR4 受体调节剂及其相关用途。在某些实施方案中，本公开涉及包含本文公开的化合物或其药学上可接受的盐或原药的药物组合物。在某些实施方案中，本文公开的组合物用于控制与CXCR4相关的病症，通常是预防或治疗病毒感染如HIV或控制癌症。
• [EN] CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USED RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR CXCR4 DE LA CHIMIOKINE ET LEURS UTILISATIONS
  申请人：UNIV EMORY

  公开号：WO2012075362A3

  公开（公告）日：2012-08-02
• CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USES RELATED THERETO
  申请人：Emory University

  公开号：EP2646430B1

  公开（公告）日：2016-09-21
• USE OF DIANHYDROGALACTITOL AND ANALOGS OR DERIVATIVES THEREOF TO TREAT NON-SMALL-CELL CARCINOMA OF THE LUNG AND OVARIAN CANCER
  申请人：Del Mar Pharmaceuticals

  公开号：EP3125920A2

  公开（公告）日：2017-02-08