4-(2-(1H-indol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)-methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine | 885675-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 4-(2-(1H-indol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)-methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine
• 英文别名: 2-(1H-Indol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine；4-[2-(1H-indol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine
• CAS: 885675-45-6
• 化学式: C₂₄H₂₈N₆O₃S₂
• 分子量: 512.657
• InChiKey: DVOPKOJKGXSSID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氯-6-(4-甲烷磺酰基-哌嗪-1-甲基)-4-吗啉-4-基-噻吩并[3,2-D]嘧啶 、 4-吲哚硼酸频那醇酯 在 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.25h， 生成 4-(2-(1H-indol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)-methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine
  参考文献：
  名称：

  Discovery of Novel PI3-Kinase δ Specific Inhibitors for the Treatment of Rheumatoid Arthritis: Taming CYP3A4 Time-Dependent Inhibition

  摘要：

  PI3K delta is a lipid kinase and a member of a larger family of enzymes, PI3K class IA(alpha, beta, delta) and IB (gamma), which catalyze the phosphorylation of PIP2 to PIP3. PI3K delta is mainly expressed in leukocytes, where it plays a critical, nonredundant role in B cell receptor mediated signaling and provides an attractive opportunity to treat diseases where B cell activity is essential, e.g., rheumatoid arthritis. We report the discovery of novel, potent, and selective PI3K delta inhibitors and describe a structural hypothesis for isoform (alpha, beta, gamma) selectivity gained from interactions in the affinity pocket. The critical component of our initial pharmacophore for isoform selectivity was strongly associated with CYP3A4 time-dependent inhibition (TDI). We describe a variety of strategies and methods for monitoring and attenuating TDI. Ultimately, a structure-based design approach was employed to identify a suitable structural replacement for further optimization.

  DOI：

  10.1021/jm3003747

文献信息

• Pharmaceutical compounds
  申请人：Shutteleworth Stephen

  公开号：US20090131429A1

  公开（公告）日：2009-05-21

  Fused pyrimidines of formula (I): where A is a thiophene or furan ring and R 1 -R 3 and n are defined in the specification. These compounds have activity as inhibitors of PI 3 K and may thus be used to treat diseased and disorders arising from abnormal cell growth, function or behaviour associated with PI 3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

  式(I)的融合嘧啶化合物：其中A为噻吩或呋喃环，R1-R3和n在规范中有定义。这些化合物具有抑制PI3K的活性，因此可用于治疗与PI3激酶相关的异常细胞生长、功能或行为引起的疾病和障碍，如癌症、免疫性疾病、心血管疾病、病毒感染、炎症、代谢/内分泌障碍和神经系统疾病。还描述了合成这些化合物的方法。
• PHARMACEUTICAL COMPOUNDS
  申请人：Shuttleworth Stephen J.

  公开号：US20100280027A1

  公开（公告）日：2010-11-04

  Provided herein are methods of treating diseases or disorders arising from abnormal cell growth, function or behavior associated with PI3 kinase, which method includes administering to a patient in need thereof a compound that is a fused pyrimidine of formula (I):

  本文提供了一种治疗因PI3激酶异常细胞生长、功能或行为引起的疾病或紊乱的方法，该方法包括向需要该治疗的患者施用以下化合物的融合嘧啶：(I)。
• PHOSPHOINOSITIDE 3-KINASE INHIBITORS WITH A ZINC BINDING MOIETY
  申请人：Curis, Inc.

  公开号：US20200339593A1

  公开（公告）日：2020-10-29

  The instant application relates to deazapurines, thienopyrimidines and furopyrimidines with zinc-binding moiety based derivatives and their use in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.
• US7776856B2
  申请人：——

  公开号：US7776856B2

  公开（公告）日：2010-08-17
• US8101607B2
  申请人：——

  公开号：US8101607B2

  公开（公告）日：2012-01-24