2-({5-chloro-2-[(1-ethyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)-5-[4-(2-hydroxyethyl)-1-piperazinyl]-N-methylbenzamide | 1224887-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-({5-chloro-2-[(1-ethyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)-5-[4-(2-hydroxyethyl)-1-piperazinyl]-N-methylbenzamide
• 英文别名: 2-[[5-chloro-2-[(2-ethylpyrazol-3-yl)amino]pyridin-4-yl]amino]-5-[4-(2-hydroxyethyl)piperazin-1-yl]-N-methylbenzamide
• CAS: 1224887-34-6
• 化学式: C₂₄H₃₁ClN₈O₂
• 分子量: 499.016
• InChiKey: QXKHOUIIZIXZHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-[(2,5-Di chloro-4-pyridinyl)amino]-5-[4-(2-hydroxyethyl)-1-piperazinyl]-N-methylbenzamide 、 5-氨基-1-乙基吡唑 在 palladium diacetate caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.67h， 生成 2-({5-chloro-2-[(1-ethyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)-5-[4-(2-hydroxyethyl)-1-piperazinyl]-N-methylbenzamide
  参考文献：
  名称：

  PYRAZOLYLAMINOPYRIDINES AS INHIBITORS OF FAK

  摘要：

  本发明涉及式(I)的化合物：或其药用可接受的盐，其中R1、R2、R3、R11、R12、R13、Q、Z和p如本文所述。本发明的化合物可用于治疗癌症。

  公开号：

  US20100113475A1

文献信息

• FAK inhibitor and drug combination thereof
  申请人：HINOVA PHARMACEUTICALS INC.

  公开号：US20220125788A1

  公开（公告）日：2022-04-28

  A deuterated compound as represented by formula (I) or an optical isomer, a tautomer, a pharmaceutically acceptable salt, a prodrug, a hydrate, or a solvate thereof are presented. Compared with a compound before deuteration, the deuterated compound shows better pharmacokinetics, higher maximum plasma drug concentration, higher exposure, and longer half-life, and has more excellent metabolic performance. The deuterated compound can effectively inhibit FAK activity, and has good application prospect in preparation of FAK inhibitors and/or drugs for treating cancer. In addition, the use of the deuterated compound in combination with an anti-cancer drug (such as a PD-1 inhibitor) can achieve a synergistic effect, thereby significantly improving the tumor suppression effect, and providing a better choice for clinical cancer treatment.

  本发明提供了由公式(I)所表示的氘代化合物或其光学异构体、互变异构体、药学上可接受的盐、前药、水合物或溶剂化物。与氘代化合物之前的化合物相比，氘代化合物表现出更好的药代动力学、更高的最大血浆药物浓度、更高的曝光度和更长的半衰期，并具有更出色的代谢性能。氘代化合物可以有效地抑制FAK活性，在制备FAK抑制剂和/或用于治疗癌症的药物方面具有良好的应用前景。此外，将氘代化合物与抗癌药物（如PD-1抑制剂）联合使用可以实现协同作用，从而显著提高肿瘤抑制效果，为临床癌症治疗提供更好的选择。
• [EN] FAK INHIBITOR AND DRUG COMBINATION THEREOF<br/>[FR] INHIBITEUR DE FAK ET COMBINAISON DE MÉDICAMENTS ASSOCIÉE<br/>[ZH] 一种FAK抑制剂及其联合用药物
  申请人：HINOVA PHARMACEUTICALS INC

  公开号：WO2020135442A1

  公开（公告）日：2020-07-02

  一种式(I)所示的氘代化合物或其光学异构体、互变异构体、药学上可接受的盐、前药、水合物或溶剂合物。与氘代前的化合物相比，氘代化合物显示了更优的药代动力学，更高的最高血药浓度，更高的暴露量和更长的半衰期，具有更加优异的代谢性能。而且，氘代化合物能够有效抑制FAK活性，在制备FAK抑制剂和/或治疗癌症的药物中具有非常好的应用前景。同时，氘代化合物与抗癌药物(比如PD-1抑制剂)联合使用能够发挥协同增效的作用，显著提高肿瘤抑制效果，为临床治疗癌症提供了更好的选择。 (I)
• THERAPEUTIC COMPOSITIONS, COMBINATIONS, AND METHODS OF USE
  申请人：Verastem, Inc.

  公开号：US20180177788A1

  公开（公告）日：2018-06-28

  This invention relates to methods comprising administering a FAK inhibitor and an immunotherapeutic agent such as anti-PD-1 or anti-PD-L1; that are useful in the treatment of abnormal cell growth, such as cancer, in mammals, especially humans.
• USE OF CALORIC RESTRICTION MIMETICS FOR POTENTIATING CHEMO-IMMUNOTHERAPY FOR THE TREATMENT OF CANCERS
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US20210030703A1

  公开（公告）日：2021-02-04

  In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-1. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.
• US9012479B2
  申请人：——

  公开号：US9012479B2

  公开（公告）日：2015-04-21