tert-butyl (trans-4-[2-(dimethylamino)ethyl]cyclohexyl)carbamate | 1356953-51-9

• 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 (trans-4-[2-(dimethylamino)ethyl]cyclohexyl)carbamate
• CAS: 1356953-51-9
• 化学式: C₁₅H₃₀N₂O₂
• 分子量: 270.415
• InChiKey: GTTIXUNXAHRAHG-JOCQHMNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.02
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  41.57
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (trans-4-[2-(dimethylamino)ethyl]cyclohexyl)carbamate 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 1.25h， 生成 N-((trans)-4-(2-(dimethylamino)ethyl)cyclohexyl)-1H-indole-2-carboxamide hydrochloride
  参考文献：
  名称：

  Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D₂ Receptor Through Fragmentation of a Bitopic Ligand

  摘要：

  Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)-ethyl)cyclohexyl)-1H-indole-2-carboxamide (0269652) (1) adopts a bitopic pose at one protomer of a dopamine D-2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxamide moiety of 1 extends into a secondary pocket between the extracellular ends of TM2 and TM7 within the D2R protomer. To target this putative allosteric site, we generated and characterized fragments that include and extend from the 1H-indole-2-carboxamide moiety of 1. N-Isopropyl-1H-indole-2-carboxamide (3) displayed allosteric pharmacology and sensitivity to mutations of the same residues at the top of TM2 as was observed for 1. Using 3 as an "allosteric lead", we designed and synthesized an extensive fragment library to generate novel SAR and identify N-butyl-1H-indole-2-carboxamide (11d), which displayed both increased negative cooperativity and affinity for the D2R. These data illustrate that fragmentation of extended compounds can expose fragments with purely allosteric pharmacology.

  DOI：

  10.1021/acs.jmedchem.5b00585
• 作为产物：
  描述：

  Ethyl [trans-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)cyclohe xyl]acetate 在 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 作用下， 以 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 20.5h， 生成 tert-butyl (trans-4-[2-(dimethylamino)ethyl]cyclohexyl)carbamate
  参考文献：
  名称：

  Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D₂ Receptor Through Fragmentation of a Bitopic Ligand

  摘要：

  Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)-ethyl)cyclohexyl)-1H-indole-2-carboxamide (0269652) (1) adopts a bitopic pose at one protomer of a dopamine D-2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxamide moiety of 1 extends into a secondary pocket between the extracellular ends of TM2 and TM7 within the D2R protomer. To target this putative allosteric site, we generated and characterized fragments that include and extend from the 1H-indole-2-carboxamide moiety of 1. N-Isopropyl-1H-indole-2-carboxamide (3) displayed allosteric pharmacology and sensitivity to mutations of the same residues at the top of TM2 as was observed for 1. Using 3 as an "allosteric lead", we designed and synthesized an extensive fragment library to generate novel SAR and identify N-butyl-1H-indole-2-carboxamide (11d), which displayed both increased negative cooperativity and affinity for the D2R. These data illustrate that fragmentation of extended compounds can expose fragments with purely allosteric pharmacology.

  DOI：

  10.1021/acs.jmedchem.5b00585

文献信息

• 1,5-NAPHTHYRIDINE DERIVATIVES AND MELK INHIBITORS CONTAINING THE SAME
  申请人：Onco Therapy Science, Inc.

  公开号：US20150005302A1

  公开（公告）日：2015-01-01

  The present invention directs a compound represented by formula (I).

  本发明涉及一种由式(I)所表示的化合物。
• 1,5-naphthyridine derivatives and MELK inhibitors containing the same
  申请人：OncoTherapy Science, Inc.

  公开号：US09067937B2

  公开（公告）日：2015-06-30

  The present invention directs a compound represented by formula (I).

  本发明涉及一种由式(I)表示的化合物。
• QUINOLINE DERIVATIVES AND MELK INHIBITORS CONTAINING THE SAME
  申请人：Matsuo Yo

  公开号：US20130217671A1

  公开（公告）日：2013-08-22

  The present invention directs a compound represented by formula (I).

  本发明涉及一种由公式(I)所代表的化合物。
• Quinoline derivatives and MELK inhibitors containing the same
  申请人：Matsuo Yo

  公开号：US09120749B2

  公开（公告）日：2015-09-01

  The present invention directs a compound represented by formula (I).

  本发明涉及一种由式(I)所代表的化合物。
• [EN] 1,5-NAPHTHYRIDINE DERIVATIVES AND MELK INHIBITORS CONTAINING THE SAME<br/>[FR] DÉRIVÉS DE 1,5-NAPHTYRIDINE ET INHIBITEURS DE MELK LES CONTENANT
  申请人：ONCOTHERAPY SCIENCE INC

  公开号：WO2013109388A3

  公开（公告）日：2015-02-05