N-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide | 1357095-04-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide
• 英文别名: 4-boronic acid pinacol ester-3-methoxy-N-phenylmethanesulfonamide；N-[3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanesulfonamide
• CAS: 1357095-04-5
• 化学式: C₁₄H₂₂BNO₅S
• 分子量: 327.209
• InChiKey: ZSYRBGXIUORMFG-UHFFFAOYSA-N

物化性质

• 沸点：
  450.3±55.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.37
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide 在 四(三苯基膦)钯 甲醇 、 sodium tetrahydroborate 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 16.33h， 生成 N-(4-(4-(hydroxymethyl)pyridin-3-yl)-3-methoxyphenyl)methanesulfonamide
  参考文献：
  名称：

  [EN] SULFONAMIDE COMPOUNDS USEFUL AS CYP17 INHIBITORS
  [FR] COMPOSÉS DE SULFONAMIDE UTILES EN TANT QU'INHIBITEURS DE CYP17

  摘要：

  公开的是化合物的磺胺类化合物的结构式（I）：或其立体异构体、N-氧化物、前药或其药学上可接受的盐，其中环A、R1、R2、R3、R4和R5在此处定义。还公开了使用这类化合物治疗与CYP17酶相关的疾病的方法，如癌症，并包括这类化合物的药物组合物。

  公开号：

  WO2012015723A1
• 作为产物：
  描述：

  4-溴-3-甲氧基苯胺 在 2-双环己基膦-2',6'-二甲氧基联苯 、 吡啶 、 双(乙腈)氯化钯(II) 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 N-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide
  参考文献：
  名称：

  Balancing potency, metabolic stability and permeability in pyrrolopyrimidine-based EGFR inhibitors

  摘要：

  The present study describes our continuous effort to develop epidermal growth factor receptor (EGFR) inhibitors based on the 6-aryl-pyrrolo[2,3-d]pyrimidin-4-amine scaffold. The activity-ADME space has been evaluated by synthesizing 43 new structures, including four variations of the 4-amino group and 34 different substitution patterns in the 6-aryl moiety. Most of the new pyrrolopyrimidines were highly active, with twelve analogues possessing lower IC50 values than the commercial drug Erlotinib in enzymatic assays. Ten EGFR inhibitors were also profiled in cell studies using the Ba/F3-EGFR(L858R) reporter cells, and all revealed nanomolar activity. However, some of the privileged structures in terms of potency had ADME short-comings: compounds containing amides, sulfonamides, amine and hydroxymethyl substituents in the 6-aryl group had low permeability and high efflux, derivatives having (R)-3amino-3-phenylpropan-1-ol at C-4 induced hERG inhibition properties, and metabolic lability was seen for compounds having (S)-2-methoxy-1-phenylethan-1-amine at C-4. Based on a trade-off between enzymatic activity, cellular potency and ADME properties, (S)-2-phenyl-2-((6-phenyl-7H-pyrrolo[2,3-d] pyrimidin-4-yl)amino)ethan-1-ol appeared as the most promising drug candidate. Cellular studies indicate this compound to have therapeutic use in EGFR driven diseases. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.08.068

文献信息

• 杂环化合物及其应用
  申请人：南京圣和药物研发有限公司

  公开号：CN106810557B

  公开（公告）日：2021-05-04

  本发明属于医药化学领域，涉及一类杂环化合物及其应用，具体地，本发明提供式I所示的化合物或其异构体、药学上可接受的盐、溶剂化物或前药，它们的制备方法以及含有这些化合物的药物组合物和这些化合物或组合物用于治疗病毒感染性疾病的药物中的用途。本发明的部分化合物具有较好的抑制HCV病毒的能力，非常有希望成为HCV治疗剂。
• PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS
  申请人：ALMIRALL, S.A.

  公开号：US20150291595A1

  公开（公告）日：2015-10-15

  New pyrrolotriazinone derivatives having the chemical structure of Formula (I) are disclosed; as well as process for theft preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks).

  本发明揭示了具有化学结构式（I）的新吡咯三唑酮衍生物；以及其制备过程，包括它们的药物组合物和它们作为磷脂酰肌醇3-激酶（PI3Ks）抑制剂在治疗中的用途。
• Pyrrolotriazinone derivatives as PI3K inhibitors
  申请人：ALMIRALL, S.A.

  公开号：US09388189B2

  公开（公告）日：2016-07-12

  New pyrrolotriazinone derivatives having the chemical structure of Formula (I) are disclosed; as well as process for theft preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks).

  本发明揭示了具有化学结构式（I）的新吡咯三嗪衍生物；以及制备它们的方法，包括含有它们的制药组合物和它们作为磷脂酰肌醇3-激酶（PI3Ks）抑制剂在治疗中的用途。
• Balancing potency, metabolic stability and permeability in pyrrolopyrimidine-based EGFR inhibitors
  作者：Jin Han、Silje Henriksen、Kristin G. Nørsett、Eirik Sundby、Bård Helge Hoff

  DOI：10.1016/j.ejmech.2016.08.068

  日期：2016.11

  The present study describes our continuous effort to develop epidermal growth factor receptor (EGFR) inhibitors based on the 6-aryl-pyrrolo[2,3-d]pyrimidin-4-amine scaffold. The activity-ADME space has been evaluated by synthesizing 43 new structures, including four variations of the 4-amino group and 34 different substitution patterns in the 6-aryl moiety. Most of the new pyrrolopyrimidines were highly active, with twelve analogues possessing lower IC50 values than the commercial drug Erlotinib in enzymatic assays. Ten EGFR inhibitors were also profiled in cell studies using the Ba/F3-EGFR(L858R) reporter cells, and all revealed nanomolar activity. However, some of the privileged structures in terms of potency had ADME short-comings: compounds containing amides, sulfonamides, amine and hydroxymethyl substituents in the 6-aryl group had low permeability and high efflux, derivatives having (R)-3amino-3-phenylpropan-1-ol at C-4 induced hERG inhibition properties, and metabolic lability was seen for compounds having (S)-2-methoxy-1-phenylethan-1-amine at C-4. Based on a trade-off between enzymatic activity, cellular potency and ADME properties, (S)-2-phenyl-2-((6-phenyl-7H-pyrrolo[2,3-d] pyrimidin-4-yl)amino)ethan-1-ol appeared as the most promising drug candidate. Cellular studies indicate this compound to have therapeutic use in EGFR driven diseases. (C) 2016 Elsevier Masson SAS. All rights reserved.
• [EN] SULFONAMIDE COMPOUNDS USEFUL AS CYP17 INHIBITORS<br/>[FR] COMPOSÉS DE SULFONAMIDE UTILES EN TANT QU'INHIBITEURS DE CYP17
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012015723A1

  公开（公告）日：2012-02-02

  Disclosed are sulfonamide compounds of Formula (I): or stereoisomers, N-oxides, prodrugs, or pharmaceutically acceptable salts thereof, wherein ring A, R1, R2, R3, R4 and R5 are defined herein. Also disclosed are methods of using such compounds in the treatment of conditions related to CYP17 enzyme, such as cancer, and pharmaceutical compositions comprising such compounds.

  公开的是化合物的磺胺类化合物的结构式（I）：或其立体异构体、N-氧化物、前药或其药学上可接受的盐，其中环A、R1、R2、R3、R4和R5在此处定义。还公开了使用这类化合物治疗与CYP17酶相关的疾病的方法，如癌症，并包括这类化合物的药物组合物。