2-Methyl-3-hydroxy-4,5-bis-chlormethyl-pyridin | 102694-13-3

• 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
• 英文名称: 2-Methyl-3-hydroxy-4,5-bis-chlormethyl-pyridin
• 英文别名: 4,5-Bis(chloromethyl)-2-methylpyridin-3-ol
• CAS: 102694-13-3
• 化学式: C₈H₉Cl₂NO
• 分子量: 206.072
• InChiKey: PGRGBTRGXLKHEC-UHFFFAOYSA-N

物化性质

• 沸点：
  418.8±40.0 °C(Predicted)
• 密度：
  1.349±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-Methyl-3-hydroxy-4,5-bis-chlormethyl-pyridin 在 盐酸 、 三(二亚苄基丙酮)二钯 、 1,3-二溴-5,5-二甲基海因 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 42.0h， 生成 5-(benzyloxy)-3,4,6-trimethylpyridin-2-amine
  参考文献：
  名称：

  Novel Pyridine Bioisostere of Cabozantinib as a Potent c-Met Kinase Inhibitor: Synthesis and Anti-Tumor Activity against Hepatocellular Carcinoma

  摘要：

  设计并合成了卡波替尼的两种新型生物同构体，编号为3和4。卡波替尼结构中心的苯环分别被三甲基吡啶（3）和吡啶（4）替代。令人惊讶的是，这两种化合物在1μM浓度下显示出极端对比的间叶-上皮转化因子（c-Met）抑制活性（3的抑制率为4%，4的抑制率为94%）。化合物4的IC50值为4.9 nM，与卡波替尼（5.4 nM）相似。基于配体的对接研究表明，4包含了与c-Met结合的优选构象，而3则不包括。化合物4对肝细胞癌（Hep3B和Huh7）和非小细胞肺癌（A549和H1299）细胞系的抗增殖活性优于卡波替尼，而3则没有显示出显著的抗增殖活性。此外，化合物4对肝细胞癌细胞系的肿瘤选择性高于卡波替尼。在异种移植鸡肿瘤模型中，化合物4抑制了Hep3B肿瘤生长的程度远远超过卡波替尼。本研究表明，化合物4可能是一种对抗肝细胞癌的良好治疗候选药物。

  DOI：

  10.3390/ijms22189685
• 作为产物：
  描述：

  吡哆醇盐酸盐 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以93%的产率得到2-Methyl-3-hydroxy-4,5-bis-chlormethyl-pyridin
  参考文献：
  名称：

  Synthesis and evaluation of 6-heteroarylamino-2,4,5-trimethylpyridin-3-ols as inhibitors of TNF-α-induced cell adhesion and inflammatory bowel disease

  摘要：

  通过TNF-α诱导的细胞粘附，发现了一系列新的抗炎性肠疾病（IBD）药物。

  DOI：

  10.1039/c8md00156a

文献信息

• HETEROARYLAMIDOPYRIDINOL DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME AS ACTIVE INGREDIENT FOR PREVENTION OR TREATMENT OF AUTOIMMUNE DISEASE
  申请人：Innovo Therapeutics Inc.

  公开号：EP4008718A1

  公开（公告）日：2022-06-08

  The present invention relates to a heteroarylamidopyridinol derivative and a pharmaceutical composition comprising same as an active ingredient for prevention or treatment of an autoimmune disease, specifically, inflammatory bowel disease, rheumatoid arthritis, etc. The heteroarylamidopyridinol derivative exhibits an excellent effect of inhibiting TNF-α- or IL-6-induced monocyte adhesion to gut epithelial cells and is proven to have a therapeutic effect on inflammatory bowel disease and rheumatoid arthritis in vivo. Thus, the heteroarylamidopyridinol derivative can be advantageously used for treatment of an autoimmune disease, specifically, inflammatory bowel disease or rheumatoid arthritis.

  本发明涉及一种杂芳基酰胺吡啶醇衍生物和一种药物组合物，其中包含杂芳基酰胺吡啶醇衍生物作为活性成分，用于预防或治疗自身免疫性疾病，特别是炎症性肠病、类风湿性关节炎等。杂芳基酰胺基吡啶醇衍生物在抑制 TNF-α- 或 IL-6 诱导的单核细胞粘附到肠道上皮细胞方面表现出卓越的效果，并被证明对体内的炎症性肠病和类风湿性关节炎有治疗作用。因此，杂芳基酰胺基吡啶醇衍生物可以很好地用于治疗自身免疫性疾病，特别是炎症性肠病或类风湿性关节炎。
• 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.
• BEU D. L.;BREAZU D.;FARCASANU I.;BORA G.
  作者：BEU D. L.、BREAZU D.、FARCASANU I.、BORA G.

  DOI：——

  日期：——
• BEU, L.;FARCASANU, I.;RUSSU, I.;BREAZU, D.;BORA, G., REV. CHIM., RSR, 1985, 36, N 6, 496-499
  作者：BEU, L.、FARCASANU, I.、RUSSU, I.、BREAZU, D.、BORA, G.

  DOI：——

  日期：——
• NOVEL SYNTHETIC ANTIOXIDANTS AND THEIR USES
  申请人：Lu Yansong

  公开号：US20150336884A1

  公开（公告）日：2015-11-26

  The present invention relates to synthetic organic antioxidants of small molecules. The novel dithiol-containing compounds in this invention possess strongest possible capability as both scavenger for free radicals and antioxidant. This invention is directed to novel molecules as prodrugs of the novel dithiol-containing compounds, their rational design, their feasible preparation route by means of synthetic organic chemistry, and their potential uses in application to treatment and/or prevention of major diseases associated with oxidative stress, such as Alzheimer's disease, Parkinson's disease, cancer, diabetes, HIV, acne, cardiovascular disease, renal disease, hypertension, hypercholesterolemia, hyperlipidemia, rheumatoid arthritis, inflammation, pain, aging, stroke, cataract, glaucoma, age-related macular degeneration, etc.