N-isopropyl-1-methyl-1H-indole-2-carboxamide | 61939-19-3

• 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-1-methyl-1H-indole-2-carboxamide
• 英文别名: 1-methyl-indole-2-carboxylic acid isopropylamide；1H-Indole-2-carboxamide, 1-methyl-N-(1-methylethyl)-；1-methyl-N-propan-2-ylindole-2-carboxamide
• CAS: 61939-19-3
• 化学式: C₁₃H₁₆N₂O
• mdl: MFCD24391344
• 分子量: 216.283
• InChiKey: RWLJZYPWAYQPQN-UHFFFAOYSA-N

物化性质

• 熔点：
  160-162 °C
• 沸点：
  438.8±18.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-isopropyl-1-methyl-1H-indole-2-carboxamide 在 二苯基-2-吡啶膦 、 偶氮二甲酸二异丙酯 、 叠氮磷酸二苯酯 作用下， 以 四氢呋喃 为溶剂， 以85%的产率得到1-Methyl-2-(1-propan-2-yltetrazol-5-yl)indole
  参考文献：
  名称：

  改善将位阻酰胺转化为1,5-二取代的四唑的条件

  摘要：

  描述了将酰胺转化为1，5-二取代的四唑的改进条件。最佳反应条件[偶氮二羧酸二异丙酯（DIAD），叠氮二苯基磷酰基膦（DPPA）和二苯基-2-吡啶基膦在THF中的温度为45°C]可将位阻酰胺转化为相应的四唑，收率很高。

  DOI：

  10.1016/j.tetlet.2010.01.024
• 作为产物：
  描述：

  异丙胺 、 1-甲基吲哚-2-甲酸 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90%的产率得到N-isopropyl-1-methyl-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

• Synthesis of β- and γ-Carbolinones via Pd-Catalyzed Direct Dehydrogenative Annulation (DDA) of Indole-carboxamides with Alkynes Using Air as the Oxidant
  作者：Zhuangzhi Shi、Yuxin Cui、Ning Jiao

  DOI：10.1021/ol1007839

  日期：2010.7.2

  A palladium-catalyzed direct dehydrogenative annulation (DDA) of indolecarboxamides with internal alkynes via C−H and N−H bond cleavage using air as the oxidant was developed. With this method, both β- and γ-carbolinones can be easily prepared under the mild conditions.

  有人开发了使用空气作为氧化剂，通过CH和N-H键裂解的钯催化的吲哚羧酰胺与内部炔烃的直接脱氢环化反应（DDA）。用这种方法，可以在温和的条件下容易地制备β-和γ-咔啉酮。
• Methods to treat lymphoplasmacytic lymphoma
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10597387B2

  公开（公告）日：2020-03-24

  The present invention provides compounds of any one of Formulae (I) to (V) (e.g., compounds of any one of Formulae (I-1) to (I-9)), and methods for treating Waldenström's macroglobulinemia (WM) and other B cell neoplams in a subject using the compounds. The methods comprise administering to a subject in need thereof an effective amount of the compounds. Also provided are methods to treat B cell neoplasms using the compounds in combination with inhibitors of Bruton's tyrosine kinase (BTK), interleukin-1 receptor-associated kinase 1 (IRAK1), interleukin-1 receptor-associated kinase 4 (IRAK4), bone marrow on X chromosome kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and/or a Src family kinase.

  本发明提供了式(I)至(V)中任一项的化合物(例如，式(I-1)至(I-9)中任一项的化合物)，以及使用这些化合物治疗受试者的瓦尔登斯特伦巨球蛋白血症(WM)和其他B细胞肿瘤的方法。这些方法包括向有需要的受试者施用有效量的化合物。还提供了使用化合物与布鲁顿酪氨酸激酶（BTK）、白介素-1 受体相关激酶 1（IRAK1）抑制剂联合治疗 B 细胞肿瘤的方法、白细胞介素-1 受体相关激酶 4 (IRAK4)、骨髓 X 染色体激酶 (BMX)、磷酸肌醇 3- 激酶 (PI3K)、转化生长因子 b 激活激酶-1 (TAK1)和/或 Src 家族激酶的抑制剂。
• METHODS TO TREAT LYMPHOPLASMACYTIC LYMPHOMA
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20160311807A1

  公开（公告）日：2016-10-27

  The present invention provides compounds of any one of Formulae (I) to (V) (e.g., compounds of any one of Formulae (I-1) to (I-9)), and methods for treating Waldenström's macroglobulinemia (WM) and other B cell neoplams in a subject using the compounds. The methods comprise administering to a subject in need thereof an effective amount of the compounds. Also provided are methods to treat B cell neoplasms using the compounds in combination with inhibitors of Bruton's tyrosine kinase (BTK), interleukin-1 receptor-associated kinase 1 (IRAK1), interleukin-1 receptor-associated kinase 4 (IRAK4), bone marrow on X chromosome kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and/or a Src family kinase.
• US7576117B1
  申请人：——

  公开号：US7576117B1

  公开（公告）日：2009-08-18
• US9856223B2
  申请人：——

  公开号：US9856223B2

  公开（公告）日：2018-01-02