4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidin-3-ylcarbamoyl)benzoic acid | 1401461-10-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidin-3-ylcarbamoyl)benzoic acid
• 英文别名: 4-[[1-[7-(3,4-dimethoxyanilino)-[1,3]thiazolo[5,4-d]pyrimidin-5-yl]piperidin-3-yl]carbamoyl]benzoic acid
• CAS: 1401461-10-6
• 化学式: C₂₆H₂₆N₆O₅S
• 分子量: 534.596
• InChiKey: JCBOMTUKQSSYTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  167
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  对苯二甲酸单甲酯 在 lithium hydroxide monohydrate 、 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 99.0h， 生成 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidin-3-ylcarbamoyl)benzoic acid
  参考文献：
  名称：

  [EN] THIAZOLOPYRIMIDINE COMPOUNDS
  [FR] COMPOSÉS THIAZOLOPYRIMIDINES

  摘要：

  本发明涉及使用以下式I的新型吡咯吡嗪衍生物：其中所有变量取代基如本文所述，这些衍生物是SYK抑制剂，可用于治疗自身免疫和炎症性疾病。

  公开号：

  WO2012130780A1

文献信息

• THIAZOLOPYRIMIDINE COMPOUNDS
  申请人：Hermann Johannes Cornelius

  公开号：US20120252777A1

  公开（公告）日：2012-10-04

  The present invention relates to the use of novel pyrrolopyrazine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用以下公式I的新型吡咯并吡嗪衍生物： 其中所有可变取代基均如本文所述定义，这些衍生物是SYK抑制剂，可用于治疗自身免疫性和炎症性疾病。
• [EN] THIAZOLOPYRIMIDINE COMPOUNDS<br/>[FR] COMPOSÉS THIAZOLOPYRIMIDINES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012130780A1

  公开（公告）日：2012-10-04

  The present invention relates to the use of novel pyrrolopyrazine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用以下式I的新型吡咯吡嗪衍生物：其中所有变量取代基如本文所述，这些衍生物是SYK抑制剂，可用于治疗自身免疫和炎症性疾病。
• Thiazolopyrimidine compounds
  申请人：Hermann Johannes Cornelius

  公开号：US08921383B2

  公开（公告）日：2014-12-30

  The present invention relates to the use of novel thiazolopyrimidine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用式I所示的新型噻唑嘧啶衍生物，其中所有变量取代基的定义如本文所述，这些化合物是SYK抑制剂，可用于治疗自身免疫和炎症性疾病。
• US8921383B2
  申请人：——

  公开号：US8921383B2

  公开（公告）日：2014-12-30
• Rational Design of Highly Selective Spleen Tyrosine Kinase Inhibitors
  作者：Matthew C. Lucas、David M. Goldstein、Johannes C. Hermann、Andreas Kuglstatter、Wenjian Liu、Kin Chun Luk、Fernando Padilla、Michelle Slade、Armando G. Villaseñor、Jutta Wanner、Wenwei Xie、Xiaohu Zhang、Cheng Liao

  DOI：10.1021/jm301367c

  日期：2012.12.13

  A novel approach to design selective spleen tyrosine kinase (Syk) inhibitors is described. Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of autoimmune diseases such as asthma, rheumatoid arthritis, and SLE. Fostamatinib, a Syk inhibitor that successfully completed phase II clinical trials, also exhibits some undesirable side effects. More selective Syk inhibitors could offer safer, alternative treatments. Through a systematic evaluation of the kinome, we identified Pro455 and Asn457 in the Syk ATP binding site as a rare combination among sequence aligned kinases and hypothesized that optimizing the interaction between them and a Syk inhibitor molecule would impart high selectivity for Syk over other kinases. We report the structure-guided identification of three series of selective spleen tyrosine kinase inhibitors that support our hypothesis and offer useful guidance to other researchers in the field.