4-(dihydroxyboranyl)-2-ethylbenzoic acid | 851335-16-5

• 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: 4-(dihydroxyboranyl)-2-ethylbenzoic acid
• 英文别名: 4-carboxy-3-ethylphenylboronic acid；4-Borono-2-ethylbenzoic acid
• CAS: 851335-16-5
• 化学式: C₉H₁₁BO₄
• 分子量: 193.995
• InChiKey: ANVHGPVOLVODNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.37
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(dihydroxyboranyl)-2-ethylbenzoic acid 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 potassium carbonate 、 palladium dichloride 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 152.0h， 生成 2-ethyl-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid
  参考文献：
  名称：

  在啮齿动物模型中，口服可利用的脑渗透性CAMKK2抑制剂可减少食物摄入。

  摘要：

  下丘脑CAMKK2代表了化学影响饱腹感和促进临床肥胖患者体重减轻的潜在机制。在三个相关的ATP竞争系列中鉴定了CAMKK2的一位数纳摩尔抑制剂。由于SAR通常是可转移的，因此对这三个系列进行了激酶选择性，溶解度和药代动力学特性的有限优化。最终，对2，4-二芳基7-氮杂吲哚进行了优化，以提供一种工具分子，该工具分子可有效抑制下丘脑衍生的细胞系中AMPK磷酸化，可口服生物利用，并穿过血脑屏障。当在啮齿动物中口服时，化合物4 t限制了生长素释放肽诱导的食物摄入。

  DOI：

  10.1016/j.bmcl.2018.03.034
• 作为产物：
  描述：

  在 盐酸 、 水 作用下， 以0.12 g的产率得到4-(dihydroxyboranyl)-2-ethylbenzoic acid
  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

• 1H-Pyrrolo[2,3-B]Pyridnes
  申请人：Frazee James S.

  公开号：US20090233955A1

  公开（公告）日：2009-09-17

  Derivatives of pyrrolo[2,3-b]pyridine which are useful as SGK-1 kinase inhibitors are described herein. The invention described herein also describes pharmaceutical compositions containing derivatives of pyrrolo[2,3-b]pyridine and methods of using pyrrolo[2,3-b]pyridine derivatives and pharmaceutical compositions thereof in the treatment of diseases mediated by SGK-1.

  本文描述了用作SGK-1激酶抑制剂的吡咯并[2,3-b]吡啶衍生物。本发明还描述了含有吡咯并[2,3-b]吡啶衍生物的制药组合物以及使用吡咯并[2,3-b]吡啶衍生物和其制药组合物治疗由SGK-1介导的疾病的方法。
• 1H-Pyrrolo[2,3-B]Pyridines
  申请人：Frazee James S.

  公开号：US20120238588A1

  公开（公告）日：2012-09-20

  Derivatives of pyrrolo[2,3-b]pyridine which are useful as SGK-1 kinase inhibitors are described herein. The invention described herein also describes pharmaceutical compositions containing derivatives of pyrrolo[2,3-b]pyridine and methods of using pyrrolo[2,3-b]pyridine derivatives and pharmaceutical compositions thereof in the treatment of diseases mediated by SGK-1.

  本文描述了作为SGK-1激酶抑制剂有用的吡咯[2,3-b]吡啶衍生物。本发明还描述了含有吡咯[2,3-b]吡啶衍生物的制药组合物以及使用吡咯[2,3-b]吡啶衍生物和制药组合物治疗由SGK-1介导的疾病的方法。
• WO2006/63167
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.
• An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model
  作者：Daniel J. Price、David H. Drewry、Lee T. Schaller、Brian D. Thompson、Paul R. Reid、Patrick R. Maloney、Xi Liang、Periette Banker、Richard G. Buckholz、Paula K. Selley、Octerloney B. McDonald、Jeffery L. Smith、Todd W. Shearer、Richard F. Cox、Shawn P. Williams、Robert A. Reid、Stefano Tacconi、Federico Faggioni、Chiara Piubelli、Ilaria Sartori、Michela Tessari、Tony Y. Wang

  DOI：10.1016/j.bmcl.2018.03.034

  日期：2018.6

  Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients. Single-digit nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive series. Limited optimization of kinase selectivity, solubility, and pharmacokinetic properties were undertaken on all three series, as SAR was often transferrable. Ultimately

  下丘脑CAMKK2代表了化学影响饱腹感和促进临床肥胖患者体重减轻的潜在机制。在三个相关的ATP竞争系列中鉴定了CAMKK2的一位数纳摩尔抑制剂。由于SAR通常是可转移的，因此对这三个系列进行了激酶选择性，溶解度和药代动力学特性的有限优化。最终，对2，4-二芳基7-氮杂吲哚进行了优化，以提供一种工具分子，该工具分子可有效抑制下丘脑衍生的细胞系中AMPK磷酸化，可口服生物利用，并穿过血脑屏障。当在啮齿动物中口服时，化合物4 t限制了生长素释放肽诱导的食物摄入。