2-(4-hydroxymethyl-3-methylpyridin-2-ylamino)thiazole-5-carbonitrile | 479612-68-5

• 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-(4-hydroxymethyl-3-methylpyridin-2-ylamino)thiazole-5-carbonitrile
• 英文别名: 2-(4-Hydroxymethyl-3-methyl-pyridin-2-ylamino)-thiazole-5-carbonitrile；2-[[4-(hydroxymethyl)-3-methylpyridin-2-yl]amino]-1,3-thiazole-5-carbonitrile
• CAS: 479612-68-5
• 化学式: C₁₁H₁₀N₄OS
• 分子量: 246.293
• InChiKey: DUDSPVQIFRXSAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-hydroxymethyl-3-methylpyridin-2-ylamino)thiazole-5-carbonitrile 在 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 7.0h， 生成 4-[2-(5-cyano-thiazol-2-ylamino)-3-methyl-pyridin-4-ylmethyl]-piperazine-1-carboxylic acid methylamide
  参考文献：
  名称：

  Potent N-(1,3-Thiazol-2-yl)pyridin-2-amine Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors with Excellent Pharmacokinetics and Low Affinity for the hERG Ion Channel

  摘要：

  A series of N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitors have been developed that possess optimal properties. Compounds have been discovered that exhibit excellent in vivo potency. The particular challenges of overcoming hERG binding activity and QTc increases in vivo in addition to achieving good pharmacokinetics have been acomplished by discovering a unique class of amine substituents. These compounds have a favorable kinase selectivity profile that can be accentuated with appropriate substitution.

  DOI：

  10.1021/jm049697f
• 作为产物：
  描述：

  3-甲基吡啶-4-羧酸 在 咪唑 、 tris(dibenzylideneacetone)dipalladium (0) 、 羟胺 、 双氧水 、 甲基三氧化铼(VII) 、 sodium hydride 、 氟化氢吡啶 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.0h， 生成 2-(4-hydroxymethyl-3-methylpyridin-2-ylamino)thiazole-5-carbonitrile
  参考文献：
  名称：

  Potent N-(1,3-Thiazol-2-yl)pyridin-2-amine Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors with Excellent Pharmacokinetics and Low Affinity for the hERG Ion Channel

  摘要：

  A series of N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitors have been developed that possess optimal properties. Compounds have been discovered that exhibit excellent in vivo potency. The particular challenges of overcoming hERG binding activity and QTc increases in vivo in addition to achieving good pharmacokinetics have been acomplished by discovering a unique class of amine substituents. These compounds have a favorable kinase selectivity profile that can be accentuated with appropriate substitution.

  DOI：

  10.1021/jm049697f

文献信息

• Tyrosine kinase inhibitors
  申请人：——

  公开号：US20030100567A1

  公开（公告）日：2003-05-29

  The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

  本发明涉及抑制、调节和/或调节酪氨酸激酶信号传导的化合物，包含这些化合物的组合物，以及使用它们治疗酪氨酸激酶依赖性疾病和情况的方法，例如在哺乳动物中的血管生成、癌症、肿瘤生长、动脉粥样硬化、年龄相关性黄斑变性、糖尿病性视网膜病变、炎症性疾病等。
• (5-cyano-2-thiazolyl)amino-4-pyridine tyrosine kinase inhibitors
  申请人：Bilodeau Mark T.

  公开号：US06875767B2

  公开（公告）日：2005-04-05

  The present invention relates to compounds having the formula I: which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions. The compounds of the present invention are useful in treating angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

  本发明涉及公式I的化合物，其抑制，调节和/或调节酪氨酸激酶信号传导，包含这些化合物的组合物，以及使用它们治疗酪氨酸激酶依赖性疾病和病状的方法。本发明的化合物对于治疗哺乳动物中的血管生成，癌症，肿瘤生长，动脉粥样硬化，年龄相关性黄斑变性，糖尿病视网膜病变，炎症性疾病等都有用。
• TYROSINE KINASE INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1404672A1

  公开（公告）日：2004-04-07
• US6875767B2
  申请人：——

  公开号：US6875767B2

  公开（公告）日：2005-04-05
• [EN] TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE TYROSINE KINASE
  申请人：MERCK & CO INC

  公开号：WO2003000687A1

  公开（公告）日：2003-01-03

  The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals. A compound of Formula (I) wherein n is 0 or 1; X is C-H or N, provided X is C-H if n=1 and R1 is SO¿2?-(C1-C6 alkyl) and provided that X is C-H if R?1¿ is NH(C=O)NR3H; R1 is SO¿2?-(C1-C6 alkyl), (C=O)NR?3¿H, or NH(C=O)NR3H; R2 is OH OC¿1?-C6 alkyl, C1-C6 alkyl, or halo; and R?3 is C¿1-C6 alkyl.