((1s,4s)-4-((tert-butoxycarbonyl)amino)cyclohexyl)methyl methanesulfonate | 1069120-41-7

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: ((1s,4s)-4-((tert-butoxycarbonyl)amino)cyclohexyl)methyl methanesulfonate
• 英文别名: ((cis)-4-((tert-butoxycarbonyl)amino)cyclohexyl)methyl methanesulfonate
• CAS: 1069120-41-7
• 化学式: C₁₃H₂₅NO₅S
• 分子量: 307.411
• InChiKey: JRZCCUKNNXDEIG-PHIMTYICSA-N

物化性质

• 沸点：
  458.0±14.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.05
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  81.7
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ((1s,4s)-4-((tert-butoxycarbonyl)amino)cyclohexyl)methyl methanesulfonate 在 盐酸 、 sodium azide 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 benzyl (((cis)-4-(3-(4-(2-(methylthio)ethoxy)phenyl)ureido)cyclohexyl)methyl)carbamate
  参考文献：
  名称：

  吲哚胺2,3-双加氧酶抑制剂与应用

  摘要：

  本发明属于医药技术领域，具体涉及式I所示的化合物、其药学上可接受的盐、异构体和前药，R1、R2、R3、X、m、n及环A如说明书中所定义；本发明还涉及这些化合物药物制剂、药物组合物及其在吲哚胺2,3‑双加氧酶(IDO)介导的相关疾病中的治疗用途，尤其是治疗与癌症有关的肿瘤特异性免疫抑制，增强抗癌症治疗的有效性。

  公开号：

  CN107793360B
• 作为产物：
  描述：

  cis-4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid methyl ester 在 甲醇 、 锂硼氢 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.75h， 生成 ((1s,4s)-4-((tert-butoxycarbonyl)amino)cyclohexyl)methyl methanesulfonate
  参考文献：
  名称：

  D₂ Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine

  摘要：

  Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both G(i/o)-biased and beta-arrestin2-biased D-2 receptor agonists based on the Food and Drug Administration (FDA)-approved drug aripiprazole. In this work, based on another FDA-approved drug, cariprazine, we conducted a structure-functional selectivity relationship study and discovered compound 38 (MS1768) as a potent partial agonist that selectively activates the G(i/o) pathway over beta-arrestin2. Unlike the dual D2R/D3R partial agonist cariprazine, compound 38 showed selective agonist activity for D2R over D3R. In fact, compound 38 exhibited potent antagonism of dopamine-stimulated beta-arrestin2 recruitment. In our docking studies, compound 38 directly interacts with S193(5.42) on TM5 but has no interactions with extracellular loop 2, which appears to be in contrast to the binding poses of D2R beta-arrestin2-biased ligands. In in vivo studies, compound 38 showed high D2R receptor occupancy in mice and effectively inhibited phencyclidine-induced hyperlocomotion.

  DOI：

  10.1021/acs.jmedchem.9b00508

文献信息

• [EN] IMIDAZOPYRIDINE DERIVATIVES AS JAK INHIBITORS<br/>[FR] DÉRIVÉS DE L'IMIDAZOPYRIDINE EN TANT QU'INHIBITEURS DE JAK
  申请人：ALMIRALL SA

  公开号：WO2011076419A1

  公开（公告）日：2011-06-30

  New imidazopyridine derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

  新的咪唑吡啶衍生物具有化学结构式(I)所示；以及它们的制备方法，包含它们的药物组合物以及它们作为Janus激酶（JAK）抑制剂在治疗中的用途。
• Discovery of potent, orally bioavailable in vivo efficacious antagonists of the TLR7/8 pathway
  作者：Phil B. Alper、Jonathan Deane、Claudia Betschart、David Buffet、Géraldine Collignon Zipfel、Perry Gordon、Janice Hampton、Stuart Hawtin、Maureen Ibanez、Tao Jiang、Tobias Junt、Thomas Knoepfel、Bo Liu、Jillian Maginnis、Una McKeever、Pierre-Yves Michellys、Daniel Mutnick、Bishnu Nayak、Satoru Niwa、Wendy Richmond、James S. Rush、Peter Syka、Yi Zhang、Xuefeng Zhu

  DOI：10.1016/j.bmcl.2020.127366

  日期：2020.9

  as a hit that showed antagonistic activity on TLR7 and TLR8 but not TLR9, as shown on human peripheral blood mononuclear cells (hPBMCs). It was functionally cross reactive with mouse TLR7 but lacked oral exposure and had only modest potency. Chemical optimization resulted in 2, which showed in vivo efficacy following intraperitoneal administration. Further optimization resulted in 8 which had excellent

  已经假设Toll样受体（TLRs）7和TLR8的拮抗作用对患有自身免疫病的患者是有益的。在鼠P4H1细胞系中进行了TLR7 / 8小分子拮抗剂的表型筛选。如人类外周血单核细胞（hPBMCs）所示，化合物1被确定为对TLR7和TLR8表现出拮抗活性但对TLR9没有拮抗作用的命中。它在功能上与小鼠TLR7有交叉反应，但缺乏口服暴露，且效力适中。化学优化产生2，其在腹膜内给药后显示出体内功效。进一步优化后得到8个，它们具有出色的体外活性，暴露能力和体内活性。改善物理特性的其他工作产生了15种先进的铅，具有良好的体外和暴露特性。进一步证明，该系列的活性随与TLR7的胞外域的结合而被追踪，这暗示该系列的靶标是内体TLR而不是下游信号传导途径。
• [EN] ARYL SULPHONE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS<br/>[FR] DÉRIVÉS D'ARYL SULFONES COMME BLOQUEURS DES CANAUX CALCIQUES
  申请人：ZALICUS PHARMACEUTICALS LTD

  公开号：WO2011035159A1

  公开（公告）日：2011-03-24

  Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted N-type and/or T-type calcium channel activity, are disclosed. Specifically, a series of compounds containing aryl sulphone derivatives, as exemplified by Formula (I).

  揭示了在改善以不需要的钙通道活性为特征的情况下有效的方法和化合物，特别是不需要的N型和/或T型钙通道活性。具体来说，包含芳基磺酰基衍生物的一系列化合物被列举为示例，如公式（I）所示。
• Antitumor Compounds Based on a Natural Product Consensus Pharmacophore
  作者：Chandraiah Lagisetti、Alan Pourpak、Qin Jiang、Xiaoli Cui、Tinopiwa Goronga、Stephan W. Morris、Thomas R. Webb

  DOI：10.1021/jm8006195

  日期：2008.10.9

  We report the design and highly enantioselective synthesis of a potent analogue of the spliceosome inhibitor FR901464, based on a non-natural product scaffold. The design of this compound was facilitated by a pharmacophore hypothesis that assumed key interaction types that are common to FR901464 and an otherwise unrelated natural product (pladienolide). The synthesis allows for the preparation of numerous

  我们报告了基于非天然产物支架的剪接体抑制剂 FR901464 的有效类似物的设计和高度对映选择性合成。药效团假设促进了该化合物的设计，该假设假设了 FR901464 和其他不相关的天然产物（pladienolide）共有的关键相互作用类型。该合成允许制备许多新型类似物。我们展示了该化合物对几种肿瘤细胞系的体外活性结果。
• ARYL SULPHONE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
  申请人：Pajouhesh Hassan A.

  公开号：US20120245137A1

  公开（公告）日：2012-09-27

  Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted N-type and/or T-type calcium channel activity, are disclosed. Specifically, a series of compounds containing aryl sulphone derivatives, as exemplified by Formula (I).

  本发明揭示了对于以不需要的钙通道活性，特别是不需要的N型和/或T型钙通道活性为特征的情况，有效改善的方法和化合物。具体地，本发明揭示了一系列含有芳基磺酰衍生物的化合物，例如公式（I）所示。