DDR1 inhibitor 7rh | 1429617-90-2

• 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: DDR1 inhibitor 7rh
• 英文别名: DDR1 7RH；4-Ethyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide；4-ethyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide
• CAS: 1429617-90-2
• 化学式: C₃₀H₂₉F₃N₆O
• 分子量: 546.595
• InChiKey: DDLPXZXBWGJRGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  methyl 4-ethyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)-benzoate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 DDR1 inhibitor 7rh
  参考文献：
  名称：

  Discovery and Optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as Novel Selective and Orally Bioavailable Discoidin Domain Receptor 1 (DDR1) Inhibitors

  摘要：

  Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)-benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, respectively, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that 7rh bound with DDR1 with a K-d value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of 7rh were 0.035 and 0.008, respectively. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, respectively.

  DOI：

  10.1021/jm301824k

文献信息

• Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
  申请人：The Board of Regents of the University of Texas System

  公开号：US10370360B2

  公开（公告）日：2019-08-06

  Compounds of formula (I), their pharmaceutically acceptable salts and stereoisomers thereof, as well as application in effectively inhibiting the enzymatic activity of discoidin domain receptor 1 and can be used as new therapeutic agents for preventing and treating e.g. inflammation, liver fibrosis, kidney fibrosis, lung fibrosis, skin scar, atherosclerosis, and cancer. The compound of formula I is: wherein the variables are as defined herein.

  式（I）化合物及其药学上可接受的盐类和立体异构体可有效抑制盘状蛋白结构域受体 1 的酶活性，可用作预防和治疗炎症、肝纤维化、肾纤维化、肺纤维化、皮肤疤痕、动脉粥样硬化和癌症等疾病的新治疗剂。式 I 的化合物为： 其中变量如本文所定义。
• Methods of treating or alleviating joint diseases by administering an inhibitor of discoidin domain receptor 1 (DDR1)
  申请人：Kaohsiung Medical University

  公开号：US10946021B2

  公开（公告）日：2021-03-16

  The present invention relates to a use of Discoidin Domain Receptor 1 (DDR1) inhibitor in preparing a medicament for preventing or treating a joint disease. The present invention further relates to a use of DDR1 activator in preparing a medicament for preventing or treating abnormalities of endochondral ossification-related conditions.

  本发明涉及类盘素域受体1（DDR1）抑制剂在制备预防或治疗关节疾病的药物中的用途。本发明进一步涉及 DDR1 激活剂在制备预防或治疗软骨内骨化异常相关疾病的药物中的用途。
• SMALL-MOLECULE INHIBITORS TARGETING DISCOIDIN DOMAIN RECEPTOR 1 AND USES THEREOF
  申请人：The Board of Regents of the University of Texas System

  公开号：US20180022730A1

  公开（公告）日：2018-01-25

  Compounds of formula (I), their pharmaceutically acceptable salts and stereoisomers thereof, as well as application in effectively inhibiting the enzymatic activity of discoidin domain receptor 1 and can be used as new therapeutic agents for preventing and treating e.g. inflammation, liver fibrosis, kidney fibrosis, lung fibrosis, skin scar, atherosclerosis, and cancer. The compound of formula I is: wherein the variables are as defined herein.
• INHIBITOR AND ACTIVATOR OF DISCOIDIN DOMAIN RECEPTOR 1 AND THEIR USE
  申请人：Kaohsiung Medical University

  公开号：US20200030332A1

  公开（公告）日：2020-01-30

  The present invention relates to a use of Discoidin Domain Receptor 1 (DDR1) inhibitor in preparing a medicament for preventing or treating a joint disease. The present invention further relates to a use of DDR1 activator in preparing a medicament for preventing or treating abnormalities of endochondral ossification-related conditions.
• Phosphatase Binding Compounds and Methods of Using Same
  申请人：Yale University

  公开号：US20200268897A1

  公开（公告）日：2020-08-27

  The present invention provides bifunctional compounds that efficiently dephosphorylate certain phospho-activated target proteins. Such target proteins can be any protein involved in the pathway of a disease or disorder, such as but not limited to cancer, neurodegeneration, metabolic disease, diabetes, insulin resistance, and so forth.