3-氨基-6-溴-5-氯吡啶甲酸甲酯 | 866775-12-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3-氨基-6-溴-5-氯吡啶甲酸甲酯
• 英文名称: methyl 3-amino-6-bromo-5-chloropicolinate
• 英文别名: methyl 3-amino-6-bromo-5-chloropyridine-2-carboxylate
• CAS: 866775-12-4
• 化学式: C₇H₆BrClN₂O₂
• 分子量: 265.494
• InChiKey: MSFXDHAGWDLGPL-UHFFFAOYSA-N

物化性质

• 沸点：
  376.8±37.0 °C(Predicted)
• 密度：
  1.758±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  65.2
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  3-氨基-6-溴-5-氯吡啶甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 水 、 sodium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 19.5h， 生成 3-(4-(tert-butyl)benzamido)-5-chloro-6-phenylpicolinic acid
  参考文献：
  名称：

  Dual-Stage Picolinic Acid-Derived Inhibitors of Toxoplasma gondii

  摘要：

  Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the first step in the glycolysis pathway, along with a larger collection of new structural derivatives. The focused screen of 22 compounds showed a 77% hit rate (>50% multistage inhibition) and revealed a series of aminobenzamide-linked picolinic acids with submicromolar potency against both T. gondii parasite forms. Picolinic acid 23, designed from an antiparasitic benzamidobenzoic acid class with challenging ADME properties, showed 60-fold-enhanced solubility, a moderate LogD_7.4, and a 30% improvement in microsomal stability. Furthermore, isotopically labeled glucose tracing revealed that picolinic acid 23 does not function by hexokinase inhibition. Thus, we report a new probe scaffold to interrogate dual-stage inhibition of T. gondii.

  DOI：

  10.1021/acsmedchemlett.0c00267
• 作为产物：
  描述：

  3- 氨基-5-氯-2-羧酸 在 甲醇 、 硫酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 36.0h， 生成 3-氨基-6-溴-5-氯吡啶甲酸甲酯
  参考文献：
  名称：

  Dual-Stage Picolinic Acid-Derived Inhibitors of Toxoplasma gondii

  摘要：

  Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the first step in the glycolysis pathway, along with a larger collection of new structural derivatives. The focused screen of 22 compounds showed a 77% hit rate (>50% multistage inhibition) and revealed a series of aminobenzamide-linked picolinic acids with submicromolar potency against both T. gondii parasite forms. Picolinic acid 23, designed from an antiparasitic benzamidobenzoic acid class with challenging ADME properties, showed 60-fold-enhanced solubility, a moderate LogD_7.4, and a 30% improvement in microsomal stability. Furthermore, isotopically labeled glucose tracing revealed that picolinic acid 23 does not function by hexokinase inhibition. Thus, we report a new probe scaffold to interrogate dual-stage inhibition of T. gondii.

  DOI：

  10.1021/acsmedchemlett.0c00267

文献信息

• [EN] COMPOUNDS AND METHODS FOR TREATING DYSLIPIDEMIA<br/>[FR] COMPOSES ET PROCEDES DESTINES AU TRAITEMENT DE LA DYSLIPIDEMIE
  申请人：LILLY CO ELI

  公开号：WO2005097805A1

  公开（公告）日：2005-10-20

  The present invention discloses compounds of formula I wherein A, n, m, j, q, K, W, X, K, Z, R1, R2, R3, R4, R5, and R6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and its sequelae.

  本发明揭示了公式I的化合物，其中A、n、m、j、q、K、W、X、K、Z、R1、R2、R3、R4、R5和R6如本文所定义，并公开了它们的药物组合物和使用方法，用于治疗血脂异常及其后续症。
• COMPOUNDS AND METHODS FOR TREATING DYSLIPIDEMIA
  申请人：Bell Gregory Michael

  公开号：US20070208003A1

  公开（公告）日：2007-09-06

  The present invention discloses compounds of formula I wherein A, n, m, j, q, y, W, X, Y, Z, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and its sequelae.

  本发明揭示了式I的化合物，其中A，n，m，j，q，y，W，X，Y，Z，R1，R2，R3，R4，R5和R6如本文所定义，并揭示了它们的药物组成物和使用方法，被用于治疗血脂异常及其后遗症。
• COMPOUNDS FOR TREATING DYSLIPIDEMIA
  申请人：ELI LILLY AND COMPANY

  公开号：EP1732933B1

  公开（公告）日：2008-07-23
• TOLL LIKE RECEPTOR MODULATOR COMPOUNDS
  申请人：Gilead Sciences, Inc.

  公开号：US20170281627A1

  公开（公告）日：2017-10-05

  The present disclosure relates generally to toll like receptor modulator compounds, such as diamino pyrido[3,2 D] pyrimidine compounds and pharmaceutical compositions which, among other things, modulate toll-like receptors (e.g. TLR-8), and methods of making and using them.
• Dual-Stage Picolinic Acid-Derived Inhibitors of <i>Toxoplasma gondii</i>
  作者：Muhammad M. Khalifa、Bruno Martorelli Di Genova、Sarah G. McAlpine、Gina M. Gallego-Lopez、David M. Stevenson、Soren D. Rozema、Neil P. Monaghan、James C. Morris、Laura J. Knoll、Jennifer E. Golden

  DOI：10.1021/acsmedchemlett.0c00267

  日期：2020.12.10

  Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the first step in the glycolysis pathway, along with a larger collection of new structural derivatives. The focused screen of 22 compounds showed a 77% hit rate (>50% multistage inhibition) and revealed a series of aminobenzamide-linked picolinic acids with submicromolar potency against both T. gondii parasite forms. Picolinic acid 23, designed from an antiparasitic benzamidobenzoic acid class with challenging ADME properties, showed 60-fold-enhanced solubility, a moderate LogD_7.4, and a 30% improvement in microsomal stability. Furthermore, isotopically labeled glucose tracing revealed that picolinic acid 23 does not function by hexokinase inhibition. Thus, we report a new probe scaffold to interrogate dual-stage inhibition of T. gondii.