2'-氟-N-(4-羟基苯基)-[1,1'-联苯]-4-丁酰胺 | 41179-33-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2'-氟-N-(4-羟基苯基)-[1,1'-联苯]-4-丁酰胺
• 英文名称: 4-(2′-fluoro-[1,1′-biphenyl]-4-yl)-N-(4-hydroxyphenyl)butanamide
• 英文别名: MK2a Inhibitor；4-(2'-fluorobiphenyl-4-yl)-N-(4-hydroxyphenyl)-butyramide；4-[4-(2-fluorophenyl)phenyl]-N-(4-hydroxyphenyl)butanamide
• CAS: 41179-33-3
• 化学式: C₂₂H₂₀FNO₂
• 分子量: 349.405
• InChiKey: ODYAQBDIXCVKAE-UHFFFAOYSA-N

物化性质

• 熔点：
  128-130 °C
• 沸点：
  585.0±50.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)
• 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)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

CMPD1 是一种选择性且非 ATP 竞争性的 p38 MAPK 介导的 MK2 磷酸化抑制剂，表观 Ki (Kiapp) 值为 330 nM。

靶点

• Ki^app: 330 nM (MK2 phosphorylation)

体外研究

CMPD1 不抑制 p38 MAPK 介导的 MBP 和 ATF2 的磷酸化。它在 U87 细胞中诱导有丝分裂停滞和凋亡，并且能够抑制胶质母细胞瘤细胞中的微管聚合。

反应信息

• 作为产物：
  描述：

  4-{2'-fluoro-[1,1'-biphenyl]-4-yl}butanoic acid 、 对氨基苯酚 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以15%的产率得到2'-氟-N-(4-羟基苯基)-[1,1'-联苯]-4-丁酰胺
  参考文献：
  名称：

  Synthesis and in vivo activity of MK2 and MK2 substrate-selective p38αMAPK inhibitors in Werner syndrome cells

  摘要：

  A benzopyranopyridine inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2) is prepared rapidly and efficiently in one step using microwave dielectric heating, whereas a substrate-selective p38 MAPK inhibitor was prepared using conventional heating techniques. The former had MK2 inhibitory activity above 2.5 mu M concentration, whereas the latter showed no MK2 inhibition at 10 mu M. However, rather than rescuing the reduced cellular growth rate and aged morphology of hTERT-immortalised WS dermal fibroblasts, both induce a state resembling stress-induced cellular senescence, suggesting that these inhibitors may have limited therapeutic use. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.036

文献信息

• TUBULIN INHIBITORS
  申请人：Lin BioScience, LLC

  公开号：US20190169127A1

  公开（公告）日：2019-06-06

  Provided herein are compounds, pharmaceutical compositions, and methods of treatment for various diseases, such as cancer. In one aspect, the method comprises the treatment of brain cancers or metastatic cancers that spread to the brain.

  本文提供了化合物、药物组合物以及治疗各种疾病（如癌症）的方法。在一个方面，该方法包括治疗脑癌或转移至大脑的癌症。
• [EN] ANTI-CANCER COMPOUNDS<br/>[FR] COMPOSÉS ANTICANCÉREUX
  申请人：UNIV SYDNEY

  公开号：WO2019148244A1

  公开（公告）日：2019-08-08

  The present invention relates to new pharmaceutical agents, and to their use in the treatment of proliferative diseases, such as cancer (in particular, brain cancer).

  本发明涉及新的药物制剂，以及它们在治疗增殖性疾病（特别是脑癌）中的应用。
• MODULATION OF GEL TEMPERATURE OF POLOXAMER-CONTAINING FORMULATIONS
  申请人：Otonomy, Inc.

  公开号：EP3508197A1

  公开（公告）日：2019-07-10

  Disclosed herein are methods for modulation of gel temperature of poloxamer-containing formulations. Also described herein are sustained release pharmaceutical formulations that gel upon contact with the body and are administered by direct application of these compositions and formulations onto or via perfusion into the targeted structure(s).

  本文公开了调节含聚氧乙烯酰胺制剂凝胶温度的方法。本文还描述了持续释放药物制剂，这些制剂与人体接触后会凝胶化，可通过将这些组合物和制剂直接涂抹在目标结构上或灌注到目标结构中进行给药。
• Pretargeted activatable cell penetrating peptide with intracellularly releasable prodrug
  申请人：The Regents of the University of California

  公开号：US10029017B2

  公开（公告）日：2018-07-24

  Disclosed herein, the invention pertains to methods and compositions that find use in treatment, diagnosis, prognosis and characterization of disease and disease samples based on the ability of a disease sample to cleave a MTS molecule of the present invention. The MTS molecules of the present invention have a formula as disclosed herein and wherein A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X and Y are linkers; P is a pre-targeting moiety; M is a macromolecular carrier, C is a detectable moiety; and T is a compound for delivery to a target, including for example a therapeutic compound.

  在此公开的本发明涉及根据疾病样本裂解本发明的 MTS 分子的能力用于疾病和疾病样本的治疗、诊断、预后和表征的方法和组合物。本发明的 MTS 分子具有如本文所公开的式，其中 A 是多肽，其序列包括 5 至 9 个连续的酸性氨基酸，其中氨基酸选自天冬氨酸和谷氨酸；B 是多肽，其序列包括 5 至 20 个连续的碱性氨基酸；X 和 Y 是连接体；P 是预靶向分子；M 是大分子载体；C 是可检测分子；T 是用于递送至靶点的化合物，例如包括治疗化合物。
• Personalized protease assay to measure protease activity in neoplasms
  申请人：The Regents of the University of California

  公开号：US10385380B2

  公开（公告）日：2019-08-20

  Disclosed herein, the invention pertains to methods and compositions that find use in diagnostic, prognostic and characterization of neoplasia samples based on the ability of a neoplasia sample to cleave a MTS molecule of the present invention. In some embodiments, a MTS molecule disclosed herein has the formula (A-X-B-C), wherein A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and C is a detectable moiety.

  本发明涉及根据肿瘤样本裂解本发明 MTS 分子的能力，用于诊断、预后和表征肿瘤样本的方法和组合物。在一些实施方案中，本发明公开的 MTS 分子具有式（A-X-B-C），其中 A 是多肽，其序列包括 5 至 9 个连续的酸性氨基酸，其中氨基酸选自天冬氨酸和谷氨酸；B 是多肽，其序列包括 5 至 20 个连续的碱性氨基酸；X 是连接体；C 是可检测分子。