N-isopropyl-1H-indole-2-carboxamide | 106024-54-8

• 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-isopropyl-1H-indole-2-carboxamide
• 英文别名: N-(Propan-2-yl)-1H-indole-2-carboxamide；N-propan-2-yl-1H-indole-2-carboxamide
• CAS: 106024-54-8
• 化学式: C₁₂H₁₄N₂O
• mdl: MFCD10666997
• 分子量: 202.256
• InChiKey: FAIUHDKHIFKHPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-isopropyl-1H-indole-2-carboxamide 在 碳酸氢钠 、 Selectfluor 作用下， 以 水 、 乙腈 为溶剂， 反应 5.0h， 以46%的产率得到3-fluoro-N-isopropyl-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
• 作为产物：
  描述：

  吲哚-2-羧酸 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 5.0h， 生成 N-isopropyl-1H-indole-2-carboxamide
  参考文献：
  名称：

  碱介导的化学选择性和区域选择性 (4+2) 吲哚-2-甲酰胺与 2,3-环氧甲苯磺酸盐成环反应生成 1,2-稠合吲哚

  摘要：

  已经探索了吲哚-2-甲酰胺与 2,3-环氧甲苯磺酸盐的碱介导[4+2]环化。该方案以非对映选择性方式以高产率提供 3-取代的吡嗪[1,2- a ]吲哚-1-酮，并且既不产生 4-取代的吡嗪[1,2- a ]吲哚-1-酮，也不产生四氢-1 H-无论远端环氧化物C3取代基是烷基还是芳基，或者环氧化物是顺式还是反式，都会生成[1,4]二氮杂[1,2- a ]吲哚-1-酮-配置。该反应通过用 2,3-环氧甲苯磺酸酯对吲哚支架进行 N-烷基化，同时进行 6-外选择性环氧化物开环反应，在一锅中进行。值得注意的是，该过程对于两种起始材料都具有化学和区域选择性。据我们所知，该过程代表了吲哚基二杂核亲核试剂与环氧化物基介电试剂一锅成环的第一个成功例子。

  DOI：

  10.1021/acs.joc.3c00813

文献信息

• Pyrrolidine amide compounds as histone demethylase inhibitors
  申请人：GENENTECH, INC.

  公开号：US10022354B2

  公开（公告）日：2018-07-17

  The present invention relates to compounds useful as inhibitors of one or more histone demethylases, such as KDM5. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

  本发明涉及可用作一种或多种组蛋白去甲基化酶（如 KDM5）抑制剂的化合物。本发明还提供了包含本发明化合物的药学上可接受的组合物，以及使用所述组合物治疗各种疾病的方法。
• Inhibitors of cysteine proteases and methods of use thereof
  申请人：Pardes Biosciences, Inc.

  公开号：US11174231B1

  公开（公告）日：2021-11-16

  The disclosure provides compounds with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease.

  本公开提供了带有弹头的化合物及其在治疗医学疾病或失调（如病毒感染）中的用途。提供了药物组合物和制造各种带弹头化合物的方法。这些化合物可用于抑制蛋白酶，如 3C、CL 或 3CL 样蛋白酶。
• [EN] MODIFIER OF FOUR-MEMBERED RING DERIVATIVE, PREPARATION METHOD AND APPLICATION THEREOF<br/>[FR] MODIFICATEUR DE DÉRIVÉ CYCLIQUE À QUATRE CHAÎNONS, PROCÉDÉ DE PRÉPARATION ET APPLICATION DE CELUI-CI<br/>[ZH] 四元环类衍生物调节剂、其制备方法和应用
  申请人：SHANGHAI HANSOH BIOMEDICAL CO LTD

  公开号：WO2021083246A1

  公开（公告）日：2021-05-06

  提供一种四元环类衍生物调节剂、其制备方法和应用。特别地，提供通式(IX-A)所示的化合物、其制备方法及含有该化合物的药物组合物，及其作为G蛋白耦联受体调节剂在治疗或预防中枢神经系统疾病和/或精神疾病的用途。其中通式(IX-A)中的各取代基与说明书中的定义相同。
• Synthesis and Pharmacological Characterization of Novel <i>trans</i>-Cyclopropylmethyl-Linked Bivalent Ligands That Exhibit Selectivity and Allosteric Pharmacology at the Dopamine D₃ Receptor (D₃R)
  作者：Vivek Kumar、Amy E. Moritz、Thomas M. Keck、Alessandro Bonifazi、Michael P. Ellenberger、Christopher D. Sibley、R. Benjamin Free、Lei Shi、J. Robert Lane、David R. Sibley、Amy Hauck Newman

  DOI：10.1021/acs.jmedchem.6b01688

  日期：2017.2.23

  The development of bitopic ligands directed toward D-2-like receptors has proven to be of particular interest to improve the selectivity and/or affinity of these ligands and as an approach to modulate and bias their efficacies. The structural similarities between dopamine D-3 receptor (D3R)-selective molecules that display bitopic or allosteric pharmacology and those that are simply competitive antagonists are subtle and intriguing. Herein we synthesized a series of molecules in which the primary and secondary pharmaco-phores were derived from the D3R-selective antagonists SB269,652 (1) and SB277011A (2) whose structural similarity and pharmacological disparity provided the perfect templates for SAR investigation. Incorporating a trans-cyclopropylmethyl linker between pharmacophores and manipulating linker length resulted in the identification of two bivalent noncompetitive D3R-selective antagonists, 18a and 25a, which further delineates SAR associated with allosterism at D3R and provides leads toward novel drug development.
• ALVAREZ GAVELA L.; CORREA MELGAREJO E.; CRUCES VILLALOBOS M. A.; ELORRIAG+, AN. QUIM. REAL SOC. ESP. QUIM., 82,(1986) N 2, 129-134
  作者：ALVAREZ GAVELA L.、 CORREA MELGAREJO E.、 CRUCES VILLALOBOS M. A.、 ELORRIAG+

  DOI：——

  日期：——