3-bromo-4-methoxyphenylaminoketone hydrochloride | 1435972-35-2

• 英文名称: 3-bromo-4-methoxyphenylaminoketone hydrochloride
• 英文别名: 2-Amino-1-(3-bromo-4-methoxyphenyl)ethan-1-onehydrochloride；2-amino-1-(3-bromo-4-methoxyphenyl)ethanone;hydrochloride
• CAS: 1435972-35-2
• 化学式: C₉H₁₀BrNO₂*ClH
• 分子量: 280.549
• InChiKey: HDHZBSFGQHTVCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  14.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.32
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-bromo-4-methoxyphenylaminoketone hydrochloride 在 四(三苯基膦)钯 、 tin(II) chloride dihdyrate 、 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-Tert-butyl-1-(2-hydroxyethyl)-5-[4-methoxy-3-(2-methoxypyrimidin-5-yl)phenyl]-6,7-dihydropyrazolo[4,3-e][1,4]diazepin-8-one
  参考文献：
  名称：

  Discovery of potent selective bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model. Part II: Optimization studies and demonstration of in vivo efficacy

  摘要：

  Selective phosphodiesterase 2 (PDE2) inhibitors are shown to have efficacy in a rat model of osteoarthritis (OA) pain. We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of phosphodiesterase 4 (PDE4) inhibitors, while minimizing PDE4 inhibitory activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like binding mode orthogonal to the cAMP-like binding mode found in PDE4. Extensive structure activity relationship studies ultimately led to identification of pyrazolodiazepinone, 22, which was >1000-fold selective for PDE2 over recombinant, full length PDEs 1B, 3A, 3B, 4A, 4B, 4C, 7A, 7B, 8A, 8B, 9, 10 and 11. Compound 22 also retained excellent PDE2 selectivity (241-fold to 419-fold) over the remaining recombinant, full length PDEs, 1A, 4D, 5, and 6. Compound 22 exhibited good pharmacokinetic properties and excellent oral bioavailability (F = 78%, rat). In an in vivo rat model of OA pain, compound 22 had significant analgesic activity 1 and 3 h after a single, 10 mg/kg, subcutaneous dose. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.082
• 作为产物：
  描述：

  1-(3-溴-4-甲氧基苯基)乙烯酮 在 乌洛托品 、 copper(ll) bromide 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 反应 50.0h， 生成 3-bromo-4-methoxyphenylaminoketone hydrochloride
  参考文献：
  名称：

  Toward a treatment of diabesity: In vitro and in vivo evaluation of uncharged bromophenol derivatives as a new series of PTP1B inhibitors

  摘要：

  Protein tyrosine phosphatase 1B (PTP1B) has been considered as a validated biological target for type 2 diabetes treatment, but past endeavors to develop inhibitors of PTP1B into drugs have been unsuccessful. Two challenging aspects are selective inhibition and cell permeability. A structure-based strategy was employed to develop uncharged bromophenols as a new series of PTP1B inhibitors. The most potent compound 22 (LXQ46) inhibited PTP1B with an IC50 value of 0.190 mu M, and showed remarkable selectivity over other protein tyrosine phosphatases (PTPs, 20-200 folds). In the SPR study, increasing concentrations of compound 22 led to concentration-dependent increases in binding responses, indicating that compound 22 could bind to the surface of PTP1B via noncovalent means. By treating insulin resistant C2C12 myotubes with compound 22, enhanced insulin and leptin signaling pathways were observed. Long-term oral administration of compound 22 reduced the blood glucose level of diabetic BKS db mice. The glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) in BKS db mice showed that oral administration of compound 22 could increase insulin sensitivity. In addition, long-term oral administration of compound 22 could protect mice from obesity, which was not the result of toxicity. Our pharmacokinetics results from the rat-based assays showed that orally administered compound 22 was absorbed rapidly from the gastrointestinal tract, extensively distributed to the tissues, and rapidly eliminated from the body. All these results indicate that compound 22 could serve as a qualified agent to treat type II diabetes. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.01.057