1H-Pyrrolo[2,3-b]pyridine, 3-bromo-1-[(4-methylphenyl)sulfonyl]-5-(2-naphthalenyl)- | 1187209-14-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1H-Pyrrolo[2,3-b]pyridine, 3-bromo-1-[(4-methylphenyl)sulfonyl]-5-(2-naphthalenyl)-
• 英文别名: 3-bromo-1-(4-methylphenyl)sulfonyl-5-naphthalen-2-ylpyrrolo[2,3-b]pyridine
• CAS: 1187209-14-8
• 化学式: C₂₄H₁₇BrN₂O₂S
• 分子量: 477.381
• InChiKey: DZMQZMOQIKPKKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  60.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1H-Pyrrolo[2,3-b]pyridine, 3-bromo-1-[(4-methylphenyl)sulfonyl]-5-(2-naphthalenyl)- 、 4-硼酸酯-苯乙酸甲酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors

  摘要：

  The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b] pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.051
• 作为产物：
  描述：

  、 对甲苯磺酰氯 在 四丁基硫酸氢铵 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 1H-Pyrrolo[2,3-b]pyridine, 3-bromo-1-[(4-methylphenyl)sulfonyl]-5-(2-naphthalenyl)-
  参考文献：
  名称：

  Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors

  摘要：

  The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b] pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.051

文献信息

• Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors
  作者：Marlys Hammond、David G. Washburn、Tram H. Hoang、Sharada Manns、James S. Frazee、Hiroko Nakamura、Jaclyn R. Patterson、Walter Trizna、Charlene Wu、Leonard M. Azzarano、Rakesh Nagilla、Melanie Nord、Rebecca Trejo、Martha S. Head、Baoguang Zhao、Angela M. Smallwood、Kendra Hightower、Nicholas J. Laping、Christine G. Schnackenberg、Scott K. Thompson

  DOI：10.1016/j.bmcl.2009.05.051

  日期：2009.8

  The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and 4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b] pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing. (C) 2009 Elsevier Ltd. All rights reserved.