5-bromo-3-(2,2-dimethyl-1,1-dioxo-hexahydro-1λ⁶-thiopyran-4-yl)-1H-indole-7-carboxylic acid methyl ester | 1065182-67-3

• 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: 5-bromo-3-(2,2-dimethyl-1,1-dioxo-hexahydro-1λ⁶-thiopyran-4-yl)-1H-indole-7-carboxylic acid methyl ester
• 英文别名: 5-bromo-3-(2,2-dimethyl-1,1-dioxidotetrahydro-thiopyran-4-yl)-1H-indole-7-carboxylic acid methyl ester；methyl 5-bromo-3-(2,2-dimethyl-1,1-dioxothian-4-yl)-1H-indole-7-carboxylate
• CAS: 1065182-67-3
• 化学式: C₁₇H₂₀BrNO₄S
• 分子量: 414.32
• InChiKey: UVFLTMIMFRJVII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  84.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-3-(2,2-dimethyl-1,1-dioxo-hexahydro-1λ⁶-thiopyran-4-yl)-1H-indole-7-carboxylic acid methyl ester 在 氨 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 5-bromo-3-[(4R)-2,2-dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]-1H-indole-7-carboxamide
  参考文献：
  名称：

  3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent

  摘要：

  I kappa B kinase beta (IKK beta or IKK2) is a key regulator of nuclear factor kappa B (NF-kappa B) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and physicochemical properties and have identified compounds 24 and (R)-28 as having robust in vivo activity.

  DOI：

  10.1021/acsmedchemlett.8b00291
• 作为产物：
  描述：

  2,2-dimethylthian-4-one 在 三氟甲磺酸三甲基硅酯 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 生成 5-bromo-3-(2,2-dimethyl-1,1-dioxo-hexahydro-1λ⁶-thiopyran-4-yl)-1H-indole-7-carboxylic acid methyl ester
  参考文献：
  名称：

  3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent

  摘要：

  I kappa B kinase beta (IKK beta or IKK2) is a key regulator of nuclear factor kappa B (NF-kappa B) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and physicochemical properties and have identified compounds 24 and (R)-28 as having robust in vivo activity.

  DOI：

  10.1021/acsmedchemlett.8b00291

文献信息

• INDOLE CARBOXAMIDES AS IKK2 INHIBITORS
  申请人：Boehm Jeffrey Charles

  公开号：US20120040958A1

  公开（公告）日：2012-02-16

  The invention is directed to novel indole carboxamide compounds. Specifically, the invention is directed to compounds according to formula (I): wherein R1, R2, R3, R4, and m are as defined herein. The compounds of the invention are inhibitors of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKKβ) activity, such as rheumatoid arthritis, asthma, rhinitis, and COPD (chronic obstructive pulmonary disease). Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting IKK2 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及新型吲哚羧酰胺化合物。具体而言，本发明涉及符合式(I)的化合物：其中R1、R2、R3、R4和m的定义如本文所述。本发明的化合物是IKK2的抑制剂，可用于治疗与不适当的IKK2（也称为IKKβ）活性相关的疾病，如类风湿性关节炎、哮喘、鼻炎和COPD（慢性阻塞性肺疾病）。因此，本发明进一步涉及包含本发明化合物的制药组合物。本发明还涉及使用本发明化合物或包含本发明化合物的制药组合物来抑制IKK2活性和治疗与之相关的疾病的方法。
• WO2008/118724
  申请人：——

  公开号：——

  公开（公告）日：——
• US8071584B2
  申请人：——

  公开号：US8071584B2

  公开（公告）日：2011-12-06
• US8372875B2
  申请人：——

  公开号：US8372875B2

  公开（公告）日：2013-02-12
• 3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent
  作者：Jeffrey K. Kerns、Jakob Busch-Petersen、Wei Fu、Jeffrey C. Boehm、Hong Nie、Michael Muratore、Ann Bullion、Guoliang Lin、Huijie Li、Roderick Davis、Xichen Lin、Ami S. Lakdawala、Rick Cousins、Rita Field、Jeremy Payne、David D. Miller、Paul Bamborough、John A. Christopher、Ian Baldwin、Ruth R. Osborn、John Yonchuk、Edward Webb、William L. Rumsey

  DOI：10.1021/acsmedchemlett.8b00291

  日期：2018.12.13

  I kappa B kinase beta (IKK beta or IKK2) is a key regulator of nuclear factor kappa B (NF-kappa B) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and physicochemical properties and have identified compounds 24 and (R)-28 as having robust in vivo activity.