2-[6-chloro-5-[4-[(4-fluorophenyl)methyl]piperidine-1-carbonyl]-1-methylindol-3-yl]-N,N-dimethyl-2-oxoacetamide | 309913-42-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-[6-chloro-5-[4-[(4-fluorophenyl)methyl]piperidine-1-carbonyl]-1-methylindol-3-yl]-N,N-dimethyl-2-oxoacetamide
• CAS: 309913-42-6
• 化学式: C₂₆H₂₇ClFN₃O₃
• 分子量: 484.0
• InChiKey: GUTYHDCSDBBMGW-UHFFFAOYSA-N

物化性质

• 溶解度：
  在 DMSO 中溶解度为 100 mM，在乙醇中溶解度为 100 mM

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  4

文献信息

• INDOLE-TYPE DERIVATIVES AS INHIBITORS OF p38 KINASE
  申请人：Mavunkel J. Babu

  公开号：US20070161649A1

  公开（公告）日：2007-07-12

  The invention is directed to methods to inhibit p38-α kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein represents a single or double bond; one Z 2 is CA or CR 8 A and the other is CR 1 , CR 1 2 , NR 6 or N wherein each R 1 , R 6 and R 8 is independently hydrogen or noninterfering substituent; A is —W i —COX j Y wherein Y is COR 2 or an isostere thereof and R 2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1; Z 3 is NR 7 or O; each R 3 is independently a noninterfering substituent; n is 0-3; each of L 1 and L 2 is a linker; each R 4 is independently a noninterfering substituent; m is 0-4; Z 1 is CR 5 or N wherein R 5 is hydrogen or a noninterfering substituent; each of 1 and k is an integer from 0-2 wherein the sum of 1 and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; and the distance between the atom of Ar linked to L 2 and the center of the α ring is 4.5-24 Å.

  该发明涉及使用以下式子的化合物及其药学上可接受的盐或药物组合物来抑制p38-α激酶的方法： 其中，表示单键或双键；其中一个Z2为CA或CR8A，另一个为CR1、CR12、NR6或N，其中每个R1、R6和R8都独立地为氢或非干扰基；A为—Wi—COXjY，其中Y为COR2或其同分异构体，R2为氢或非干扰基，W和X均为2-6Å的间隔，i和j均独立地为0或1；Z3为NR7或O；每个R3都是非干扰基；n为0-3；每个L1和L2都是连接基；每个R4都是非干扰基；m为0-4；Z1为CR5或N，其中R5为氢或非干扰基；每个1和k为0-2的整数，其中1和k的和为0-3；Ar为芳基基团，其上带有0-5个非干扰基，其中两个非干扰基可以形成螺环；且与L2连接的Ar原子与α环中心之间的距离为4.5-24Å。
• COMPOSITION COMPRISING A SPECIFIC P38A INHIBITOR AND AN AGENT THAT INDUCES CHROMOSOME INSTABILITY AND MEDICAL USES THEREOF
  申请人：Fundació Institut de Recerca Biomèdica (IRB Barcelona)

  公开号：EP3415164A1

  公开（公告）日：2018-12-19

  The present invention relates to compositions comprising a specific p38α inhibitor and an agent that induces chromosome instability, wherein preferably the specific p38α inhibitor has a half maximal inhibitory concentration (IC50) equal to or less than 40 nM. The invention also relates to the above compositions or to a specific p38α inhibitor for use in the treatment of breast cancer, wherein the breast cancer is characterised by a high degree of chromosome instability. Finally, the invention relates to a method for identifying a breast cancer patient who responds to a treatment with the above compositions or with a specific p38α inhibitor, wherein the breast cancer is characterised by a high degree of chromosome instability, and a method for selecting a treatment for a breast cancer patient.

  本发明涉及包含特异性 p38α 抑制剂和诱导染色体不稳定性的制剂的组合物，其中优选特异性 p38α 抑制剂的半最大抑制浓度（IC50）等于或小于 40 nM。本发明还涉及上述组合物或用于治疗乳腺癌的特异性 p38α 抑制剂，其中乳腺癌的特征是染色体高度不稳定。最后，本发明涉及一种确定对上述组合物或特定 p38α 抑制剂治疗有反应的乳腺癌患者的方法（其中乳腺癌的特征是染色体高度不稳定），以及一种为乳腺癌患者选择治疗方法的方法。
• P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD
  申请人：Fulcrum Therapeutics, Inc.

  公开号：US10342786B2

  公开（公告）日：2019-07-09

  The disclosure relates to methods and compositions including p38 kinase inhibitors and agents that regulate expression of DUX4 and downstream genes including but not restricted to ZSCAN4, LEUTX, PRAMEF2, TRIM43, MBD3L2, KHDC1L, RFPL2, CCNA1, SLC34A2, TPRX1, PRAMEF20, TRIM49, PRAMEF4, PRAME6, PRAMEF15, or ZNF280A. Methods useful for treating a disease associated with abnormal DUX4 and downstream gene expression (e.g., Fascioscapulohumeral muscular dystrophy) are disclosed.

  本发明公开了包括 p38 激酶抑制剂和调节 DUX4 及下游基因（包括但不限于 ZSCAN4、LEUTX、PRAMEF2、TRIM43、MBD3L2、KHDC1L、RFPL2、CCNA1、SLC34A2、TPRX1、PRAMEF20、TRIM49、PRAMEF4、PRAME6、PRAMEF15 或 ZNF280A）表达的制剂在内的方法和组合物。本研究公开了用于治疗与 DUX4 及下游基因表达异常有关的疾病（如筋膜囊性肌营养不良症）的方法。
• INDOLE-TYPE DERIVATIVES AS INHIBITORS OF P38 KINASE
  申请人：SCIOS INC.

  公开号：EP1178983B1

  公开（公告）日：2007-10-24
• COMPOSITIONS AND METHODS FOR TREATING ALZHEIMER'S DISEASE
  申请人：Eip Pharma, LLC

  公开号：EP2707369B1

  公开（公告）日：2016-07-27