2-(3,4-dimethoxyphenyl)-3-oxopropanenitrile | 96729-80-5

• 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: 2-(3,4-dimethoxyphenyl)-3-oxopropanenitrile
• 英文别名: α-Formyl-homoveratronitril；2-Cyano-2-(3,4-dimethoxyphenyl)acetaldehyde；2-(3,4-dimethoxy-phenyl)-3-oxo-propionitrile；2-[3,4-bis(methyloxy)phenyl]-3-oxopropanenitrile
• CAS: 96729-80-5
• 化学式: C₁₁H₁₁NO₃
• mdl: MFCD00612308
• 分子量: 205.213
• InChiKey: FNPUMVINNQFVCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-3-oxopropanenitrile 在 sodium ethanolate 、 sodium hydride 、 溶剂黄146 、 N,N-二甲基苯胺 、 肼 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 mineral oil 为溶剂， 反应 50.5h， 生成 6-bromo-3-(3,4-dimethoxyphenyl)-5-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-amine
  参考文献：
  名称：

  Efficacy and Tolerability of Pyrazolo[1,5-a]pyrimidine RET Kinase Inhibitors for the Treatment of Lung Adenocarcinoma

  摘要：

  RET (REarranged during Transfection) kinase gain-of-function aberrancies have been identified as potential oncogenic drivers in lung adenocarcinoma, along with several other cancer types, prompting the discovery and assessment of selective inhibitors. Internal mining and analysis of relevant kinase data informed the decision to investigate a pyrazolo[1,5-a]pyrimidine scaffold, where subsequent optimization led to the identification of compound WF-47-JS03 (1), a potent RET kinase inhibitor with >500-fold selectivity against KDR (Kinase insert Domain Receptor) in cellular assays. In subsequent mouse in vivo studies, compound 1 demonstrated effective brain penetration and was found to induce strong regression of RET-driven tumor xenografts at a well-tolerated dose (10 mg/kg, po, qd). Higher doses of 1, however, were poorly tolerated in mice, similar to other pyrazolo[1,5-a]pyrimidine compounds at or near the efficacious dose, and indicative of the narrow therapeutic windows seen with this scaffold.

  DOI：

  10.1021/acsmedchemlett.0c00015
• 作为产物：
  描述：

  3,4-二甲氧基苯乙腈 、 甲酸乙酯 在 乙醇 、 sodium 作用下， 以72 %的产率得到2-(3,4-dimethoxyphenyl)-3-oxopropanenitrile
  参考文献：
  名称：

  抑制FGFR4激酶的化合物及其应用

  摘要：

  本发明公开了一种通式(Ⅰ)的化合物，#imgabs0#其中，R1、R2和R3独立地为‑R、‑R'‑R、‑R'OR、‑R'SR、‑R'N(R)2、‑R'OR'OR、‑R'OR'N(R)2、‑R'OR'SR、‑R'SR'OR、‑R'SR'N(R)2、‑R'SR'SR、‑R'N(R)R'OR、‑R'N(R)R'N(R)2、‑R'N(R)R'SR、‑R'C(O)R、‑R'S(O)R、‑R'S(O)2R、‑R'C(O)N(R)2、‑R'N(R)C(O)R、‑R'C(O)OR、‑R'OC(O)R、环基、芳基或杂芳基；或R1和R2一起形成烃环、芳环、或杂芳环。本发明的通式(Ⅰ)的化合物对FGFR4酶或者细胞具有较好的抑制活性作用。

  公开号：

  CN117003747A

文献信息

• PYRAZOLO[1,5-A]PYRIMIDINES AS ANTIVIRAL COMPOUNDS
  申请人：APODEMUS AB

  公开号：US20160318937A1

  公开（公告）日：2016-11-03

  A compound of formula (I) or a pharmaceutically acceptable salt thereof, useful in therapy, in particular in the treatment of a viral infection.

  式（I）的化合物或其在治疗中有用的药用盐，特别是用于治疗病毒感染。
• Synthesis and some properties of 2,4,6-trihydroxy-3-methylbenzoic acid
  作者：D. A. Shubin、S. S. Bobylev、D. N. Kuznetsov、A. G. Ruchkina、K. I. Kobrakov

  DOI：10.1007/s11172-019-2418-2

  日期：2019.1

  Abstract2,4,6-Trihydroxy-3-methylbenzoic acid was obtained by NaHCO3 carboxylation of 2,4,6-trihydroxytoluene. The heterocyclization and esterification of the above acid were studied.

  摘要 2,4,6-三羟基甲苯经NaHCO3羧化制得2,4,6-三羟基-3-甲基苯甲酸。研究了上述酸的杂环化和酯化反应。
• Glutamine fructose-y-phosphate amidotransferase (GFAT) inhibitors
  申请人：Bolin Robert David

  公开号：US20050113407A1

  公开（公告）日：2005-05-26

  Compounds of formula (I) are provided, wherein R 1 and R 2 are as designated in the specification. The compounds have utility for the treatment of type 2 diabetes mellitus.

  提供了式(I)的化合物，其中R1和R2如规范中所指定。这些化合物具有治疗2型糖尿病的用途。
• Anaplastic lymphoma kinase modulators and methods of use
  申请人：Anand Kumar Neel

  公开号：US20070032515A1

  公开（公告）日：2007-02-08

  The present invention comprises compounds and pharmaceutical compositions comprising the compounds that are inhibitors of ALK. The invention also comprises methods of using the compounds and compositions to treat diseases mediated by ALK, including diseases such as cancer, immunological disorders, cardiovascular diseases, and other degenerative disorders.

  本发明涉及抑制ALK的化合物和药物组合物，其中药物组合物包括这些化合物。该发明还涉及使用这些化合物和组合物治疗由ALK介导的疾病的方法，包括癌症、免疫性疾病、心血管疾病和其他退行性疾病等疾病。
• PYRAZOLOPYRIMIDINES AS LIPID KINASE INHIBITORS
  申请人：Imbach Patricia

  公开号：US20090286779A1

  公开（公告）日：2009-11-19

  The invention relates to novel—at least 3,5-disubstituted-pyrazolo[1,5-a]pyrimidines of the formula I, wherein the symbols R 1 to R 4 are as defined in the specification, tautomers thereof or N-oxides thereof, or (preferably pharmaceutically acceptable) salts thereof, or hydrates or solvates thereof, as well as to related embodiments. The compounds are useful inter alia as protein kinase inhibitors, and thus e.g. useful in the treatment of diseases that respond to an inhibition of kinases of the PI3-kinase-related protein kinase family, especially lipid kinases and/or PI3 kinase (PI3K) and/or mTOR and/or DNA protein kinase and/or ATM and/or ATR and/or hSMG-1.

  本发明涉及一种新型的至少3,5-二取代吡唑并[1,5-a]嘧啶的化合物，其化学式为I，其中符号R1至R4如规范中所定义，其互变异构体或N-氧化物，或其（优选为药学上可接受的）盐，或其水合物或溶剂物，以及相关的实施例。该化合物可用作蛋白激酶抑制剂，因此例如在治疗对PI3-激酶相关蛋白激酶家族的激酶抑制有反应的疾病中有用，特别是脂质激酶和/或PI3激酶（PI3K）和/或mTOR和/或DNA蛋白激酶和/或ATM和/或ATR和/或hSMG-1。