2,4,5-trimethyl-6-(pyrrolidin-1-yl)pyridin-3-ol | 1444334-53-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2,4,5-trimethyl-6-(pyrrolidin-1-yl)pyridin-3-ol
• 英文别名: 2,4,5-Trimethyl-6-(pyrrolidin-1-yl)pyridin-3-ol；2,4,5-trimethyl-6-pyrrolidin-1-ylpyridin-3-ol
• CAS: 1444334-53-5
• 化学式: C₁₂H₁₈N₂O
• 分子量: 206.288
• InChiKey: VCPAMQFEBNYADD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  36.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 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 、 palladium 10% on activated carbon 、 氢气 、 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 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 35.0h， 生成 2,4,5-trimethyl-6-(pyrrolidin-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

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.
• METHOD OF TREATING INFLAMMATORY BOWEL DISEASE COMPRISING ADMINISTERING A PHARMACEUTICAL COMPOSITION COMPRISING A 6-AMINOPYRIDIN-3-OL COMPOUND OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AS AN ACTIVE INGREDIENT TO A SUBJECT
  申请人：Research Cooperation Foundation of Yeungnam University

  公开号：US20160354352A1

  公开（公告）日：2016-12-08

  Provided is a method of treating inflammatory bowel disease comprising administering a pharmaceutical composition comprising a 6-aminopyridin-3-ol compound or a pharmaceutically acceptable salt thereof as an active ingredient to a subject, which inhibits colitis in a model of inflammatory bowel disease, and accordingly, they may be suitable for use as a drug for the prevention or treatment of inflammatory bowel disease.
• US9452159B2
  申请人：——

  公开号：US9452159B2

  公开（公告）日：2016-09-27
• US9889139B2
  申请人：——

  公开号：US9889139B2

  公开（公告）日：2018-02-13