N-(cyclohexylmethyl)-1H-indole-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-(cyclohexylmethyl)-1H-indole-2-carboxamide
• 化学式: C₁₆H₂₀N₂O
• 分子量: 256.348
• InChiKey: VDWNDCQHKBKMMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  吲哚-2-羧酸 、 环己甲胺 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以64%的产率得到N-(cyclohexylmethyl)-1H-indole-2-carboxamide
  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

• Indole-2-carboxamide derivatives useful as beta-2 agonists
  申请人：Pfizer Limited

  公开号：EP1460064A1

  公开（公告）日：2004-09-22

  The invention relates to indole derivatives of general formula: and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The indole derivatives according to the present invention are useful in numerous diseases, disorders and conditions. In particular inflammatory, allergic and respiratory diseases, disorders and conditions.

  这项发明涉及一般式的吲哚衍生物： 以及用于制备、用于制备的中间体、含有和用途的过程。根据本发明的吲哚衍生物在许多疾病、紊乱和状况中是有用的。特别是炎症性、过敏性和呼吸系统疾病、紊乱和状况。
• Indole derivatives as histamine 3 receptor inhibitors for the treatment of cognitive and sleep disorders, obesity and other CNS disorders
  申请人：Bennani Youssef L.

  公开号：US20090036446A1

  公开（公告）日：2009-02-05

  This invention relates to compounds having pharmacological activity, to compositions containing these compounds, and to a method of treatment employing the compounds and compositions. More particularly, this invention concerns certain indole derivatives and their salts and solvates. These compounds have H 3 histamine receptor antagonist activity. This invention also relates to pharmaceutical compositions containing these compounds and to a method of treating disorders in which histamine H 3 receptor blockade is beneficial.

  本发明涉及具有药理活性的化合物、含有这些化合物的组合物以及使用这些化合物和组合物的治疗方法。更具体地说，本发明涉及某些吲哚衍生物及其盐和溶剂化物。这些化合物具有H3组胺受体拮抗活性。本发明还涉及含有这些化合物的药物组合物以及一种治疗组胺H3受体阻滞有益的疾病的方法。
• INDOLE DERIVATIVES AS HISTAMINE 3 RECEPTOR INHIBITORS FOR THE TREATMENT OF COGNITIVE AND SLEEP DISORDERS, OBESITY AND OTHER CNS DISORDERS
  申请人：Bennani Youssef L.

  公开号：US20110059966A1

  公开（公告）日：2011-03-10

  This invention relates to compounds having pharmacological activity, to compositions containing these compounds, and to a method of treatment employing the compounds and compositions. More particularly, this invention concerns certain indole derivatives and their salts and solvates. These compounds have H 3 histamine receptor antagonist activity. This invention also relates to pharmaceutical compositions containing these compounds and to a method of treating disorders in which histamine H 3 receptor blockade is beneficial.

  本发明涉及具有药理活性的化合物，含有这些化合物的组合物，以及使用这些化合物和组合物的治疗方法。更具体地，本发明涉及某些吲哚衍生物及其盐和溶剂。这些化合物具有H3组胺受体拮抗活性。本发明还涉及含有这些化合物的制药组合物以及一种治疗组胺H3受体阻断有益的疾病的方法。
• US7855224B2
  申请人：——

  公开号：US7855224B2

  公开（公告）日：2010-12-21
• US8129424B2
  申请人：——

  公开号：US8129424B2

  公开（公告）日：2012-03-06