1-(5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl)-4-methylpiperazine | 1444336-32-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl)-4-methylpiperazine
• 英文别名: 1-(5-(Benzyloxy)-3,4,6-trimethylpyridin-2-yl)-4-methylpiperazine；1-methyl-4-(3,4,6-trimethyl-5-phenylmethoxypyridin-2-yl)piperazine
• CAS: 1444336-32-6
• 化学式: C₂₀H₂₇N₃O
• 分子量: 325.454
• InChiKey: UIEYELFEMUCTDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  28.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl)-4-methylpiperazine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以99%的产率得到2,4,5-trimethyl-6-(4-methylpiperazin-1-yl)pyridin-3-ol
  参考文献：
  名称：

  6-氨基-2,4,5-三甲基吡啶-3-醇：一种新的通用合成途径和抗血管生成活性

  摘要：

  已开发出一种新的合成策略，该方法可通过六步法从吡ido醇·HCl制备多种6-氨基-2,4,5-三甲基吡啶-3-醇。这种方法的特点是，通过使用钯（Buchwald-Hartwig胺化反应），将重要的氨基引入到3-苄氧基-6-溴-2,4,5-三甲基吡啶（13）的C（6）位置，该中间体是关键中间体。 0）过渡金属，它肯定会扩大氨基取代基的范围。使用本文所述方法制备的某些类似物在鸡绒膜尿囊膜（CAM）分析中显示出高水平的抗血管生成和抗肿瘤活性，证明了这些新的氨基吡啶并作为抗血管生成剂的潜力。

  DOI：

  10.1016/j.ejmech.2014.03.045
• 作为产物：
  描述：

  吡哆醇盐酸盐 在 tris-(dibenzylideneacetone)dipalladium(0) 、 氯化亚砜 、 1,3-二溴-5,5-二甲基海因 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 sodium t-butanolate 、 锌 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 27.0h， 生成 1-(5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl)-4-methylpiperazine
  参考文献：
  名称：

  6-氨基-2,4,5-三甲基吡啶-3-醇：一种新的通用合成途径和抗血管生成活性

  摘要：

  已开发出一种新的合成策略，该方法可通过六步法从吡ido醇·HCl制备多种6-氨基-2,4,5-三甲基吡啶-3-醇。这种方法的特点是，通过使用钯（Buchwald-Hartwig胺化反应），将重要的氨基引入到3-苄氧基-6-溴-2,4,5-三甲基吡啶（13）的C（6）位置，该中间体是关键中间体。 0）过渡金属，它肯定会扩大氨基取代基的范围。使用本文所述方法制备的某些类似物在鸡绒膜尿囊膜（CAM）分析中显示出高水平的抗血管生成和抗肿瘤活性，证明了这些新的氨基吡啶并作为抗血管生成剂的潜力。

  DOI：

  10.1016/j.ejmech.2014.03.045

文献信息

• 6-AMINOPYRIDINE-3-OL DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENTS FOR PREVENTING OR TREATING DISEASES CAUSED BY ANGIOGENESIS
  申请人：Industry-Academic Cooperation Foundation Yeungnam University

  公开号：EP2796450B1

  公开（公告）日：2018-07-18
• In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease
  作者：Suhrid Banskota、Han-eol Kang、Dong-Guk Kim、Sang Won Park、Hyeonjin Jang、Ujjwala Karmacharya、Byeong-Seon Jeong、Jung-Ae Kim、Tae-gyu Nam

  DOI：10.1016/j.bmcl.2016.08.075

  日期：2016.10

  Although the pathogenesis of inflammatory bowel disease (IBD) is complex, attachment and infiltration of leukocytes to gut epithelium induced by pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) represents the initial step of inflammation in IBD. Previously, we have reported that some 6-amino-2,4,5-trimethylpyridin-3-ols have significant levels of antiangiogenic activity via PI3K inhibition. Based on the reports that angiogenesis is involved in the aggravation of IBD and that PI3K is a potential target for IBD therapy, we investigated whether the scaffold has inhibitory activity against in vitro and in vivo models of colitis. Many analogues showed >80% inhibition against TNF-alpha-induced monocyte adhesion to colon epithelial cells at 1 mu M. Compound 8m showed IC50 = 0.19 mu M, which is about five orders of magnitude better than that of 5-aminosalicylic acid (5-ASA, IC50 = 18.1 mM), a positive control. In a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, orally administered 8m dramatically ameliorated TNBS-induced colon inflammation. It was demonstrated by a high level of suppression in myeloperoxidase (MPO), a surrogate marker of colitis, as well as almost perfect recovery of colon and body weights in a dose-dependent manner. Compared to sulfasalazine, a prodrug of 5-ASA, compound 8m showed >300-fold better efficacy in those parameters. Taken together, 6-amino-2,4,5-trimethylpyridin-3-ols can provide a novel platform for anti-IBD drug discovery. (C) 2016 Elsevier Ltd. All rights reserved.
• US9452159B2
  申请人：——

  公开号：US9452159B2

  公开（公告）日：2016-09-27
• [EN] 6-AMINOPYRIDINE-3-OL DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENTS FOR PREVENTING OR TREATING DISEASES CAUSED BY ANGIOGENESIS<br/>[FR] DÉRIVÉS 6-AMINOPYRIDINE-3-OL OU LEURS SELS PHARMACEUTIQUEMENT ACCEPTABLES, ET COMPOSITION PHARMACEUTIQUE CONTENANT CES DÉRIVÉS OU CES SELS COMME PRINCIPES ACTIFS POUR LA PRÉVENTION OU LE TRAITEMENT DES MALADIES PROVOQUÉES PAR L'ANGIOGENÈSE
  申请人：UNIV YEUNGNAM IACF

  公开号：WO2013095060A1

  公开（公告）日：2013-06-27

  본 발명은 6-아미노피리딘-3-올 유도체 또는 이의 약제학적 허용가능한 염 및 이를 유효성분으로 함유하는 혈관신생으로 인한 질환의 예방 또는 치료용 약학조성물에 관한 것으로, 화학식 1로 표시되는 6-아미노피리딘-3-올 유도체 또는 이의 약제학적 허용가능한 염은 융모요막 모델에서의 신생혈관형성 억제 효과가 탁월하여, 혈관신생으로 인한 질환의 예방 또는 치료용 약제로서 유용하게 사용될 수 있다.
• 6-Amino-2,4,5-trimethylpyridin-3-ols: A new general synthetic route and antiangiogenic activity
  作者：Dong-Guk Kim、Youra Kang、Hyunji Lee、Eun Kyung Lee、Tae-gyu Nam、Jung-Ae Kim、Byeong-Seon Jeong

  DOI：10.1016/j.ejmech.2014.03.045

  日期：2014.5

  A new synthetic strategy for preparation of a wide range of 6-amino-2,4,5-trimethylpyridin-3-ols from pyridoxine·HCl via a six-step sequence has been developed. This approach features an introduction of various amino groups to C(6)-position of 3-benzyloxy-6-bromo-2,4,5-trimethylpyridine (13), a key intermediate, by a Buchwald–Hartwig amination reaction using palladium(0) transition metal, which certainly

  已开发出一种新的合成策略，该方法可通过六步法从吡ido醇·HCl制备多种6-氨基-2,4,5-三甲基吡啶-3-醇。这种方法的特点是，通过使用钯（Buchwald-Hartwig胺化反应），将重要的氨基引入到3-苄氧基-6-溴-2,4,5-三甲基吡啶（13）的C（6）位置，该中间体是关键中间体。 0）过渡金属，它肯定会扩大氨基取代基的范围。使用本文所述方法制备的某些类似物在鸡绒膜尿囊膜（CAM）分析中显示出高水平的抗血管生成和抗肿瘤活性，证明了这些新的氨基吡啶并作为抗血管生成剂的潜力。