ethyl 1-ethyl-5-methyl-1H-pyrazole-4-carboxylate | 1343032-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 1-ethyl-5-methyl-1H-pyrazole-4-carboxylate
• 英文别名: ethyl 1-ethyl-5-methylpyrazole-4-carboxylate
• CAS: 1343032-27-8
• 化学式: C₉H₁₄N₂O₂
• 分子量: 182.222
• InChiKey: YRRNJNOJXSYILN-UHFFFAOYSA-N

物化性质

• 沸点：
  260.1±20.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 1-ethyl-5-methyl-1H-pyrazole-4-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以67 %的产率得到(1-乙基-5-甲基-1H-吡唑-4-基)甲醇
  参考文献：
  名称：

  10.1002/cmdc.202400264

  摘要：

  The FK506 binding protein 51 (FKBP51) is an appealing drug target due to its role in several diseases such as depression, anxiety, chronic pain and obesity. Towards this, selectivity versus the close homolog FKBP52 is essential. However, currently available FKBP51‐selective ligands such as SAFit2 are too large and lack drug‐like properties. Here, we present a structure activity relationship (SAR) analysis of the pipecolic ester moiety of SAFit1 and SAFit2, which culminated in the discovery of the 1,4‐pyrazolyl derivative 23d, displaying a binding affinity of 0.077 µM for FKBP51, reduced molecular weight (541.7 g/mol), lower hydrophobicity (cLogP = 3.72) and higher ligand efficiency (LE = 0.25). Cocrystal structures revealed the importance of the 1,4‐ and 1,3,4‐ substitution patterns of the pyrazole ring versus the 1,4,5 arrangement.

  DOI：

  10.1002/cmdc.202400264
• 作为产物：
  描述：

  乙酰乙酸乙酯 在 盐酸 、 sodium carbonate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 1-ethyl-5-methyl-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  10.1002/cmdc.202400264

  摘要：

  The FK506 binding protein 51 (FKBP51) is an appealing drug target due to its role in several diseases such as depression, anxiety, chronic pain and obesity. Towards this, selectivity versus the close homolog FKBP52 is essential. However, currently available FKBP51‐selective ligands such as SAFit2 are too large and lack drug‐like properties. Here, we present a structure activity relationship (SAR) analysis of the pipecolic ester moiety of SAFit1 and SAFit2, which culminated in the discovery of the 1,4‐pyrazolyl derivative 23d, displaying a binding affinity of 0.077 µM for FKBP51, reduced molecular weight (541.7 g/mol), lower hydrophobicity (cLogP = 3.72) and higher ligand efficiency (LE = 0.25). Cocrystal structures revealed the importance of the 1,4‐ and 1,3,4‐ substitution patterns of the pyrazole ring versus the 1,4,5 arrangement.

  DOI：

  10.1002/cmdc.202400264

文献信息

• [EN] BENZODIAZEPINE DERIVATIVES FOR TREATING A RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION<br/>[FR] DÉRIVÉS DE BENZODIAZÉPINE POUR LE TRAITEMENT D'UNE INFECTION PAR LE VIRUS RESPIRATOIRE SYNCYTIAL (RSV)
  申请人：REVIRAL LTD

  公开号：WO2021079121A1

  公开（公告）日：2021-04-29

  Benzodiazepine derivatives of formula (I): wherein: each of R1 and R2 is independently H or halo; R3 is H, C1-C6 alkyl, -NHR8 or -OR'; either (i) a, c, and e are all bonds, with b, d and f absent; or b, d and f are all bonds, with a, c and e absent; R4 is H or a group selected from C1-C6 alkyl, C3-C6 cycloalkyl and 4- to 10-membered heterocyclyl, the group being unsubstituted or substituted; R5 is H or halo; R6 is -OR8, -NR8R9 or -R8; R7 is H or halo; each of R8 and R9 is independently H or a group selected from C1-C6 alkyl, C3-C6 cycloalkyl and 4- to 10-membered heterocyclyl, the group being unsubstituted or substituted; R' is H or C1-C6 alkyl; and one of V and W is CH and the other is N or CH; and the pharmaceutically acceptable salts thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection.

  苯二氮卓啉衍生物的结构式（I）：其中：R1和R2中的每一个独立地是H或卤素；R3是H，C1-C6烷基，-NHR8或-OR'；要么（i）a，c和e都是键，b，d和f不存在；要么b，d和f都是键，a，c和e不存在；R4是H或从C1-C6烷基，C3-C6环烷基和4-到10-成员杂环基中选择的基团，该基团未取代或取代；R5是H或卤素；R6是-OR8，-NR8R9或-R8；R7是H或卤素；R8和R9中的每一个独立地是H或从C1-C6烷基，C3-C6环烷基和4-到10-成员杂环基中选择的基团，该基团未取代或取代；R'是H或C1-C6烷基；V和W中的一个是CH，另一个是N或CH；以及其药用盐是RSV的抑制剂，因此可用于治疗或预防RSV感染。
• UREA ANTAGONISTS OF P2Y1 RECEPTOR USEFUL IN THE TREATMENT OF THROMBOTIC CONDITIONS
  申请人：Chao Hannguang J.

  公开号：US20080280905A1

  公开（公告）日：2008-11-13

  The present invention provides novel pyridyl or phenyl ureas and analogues thereof, which are selective inhibitors of the human P2Y 1 receptor. The invention also provides for various pharmaceutical compositions of the same and methods for treating diseases responsive to modulation of P2Y 1 receptor activity.

  本发明提供了新型吡啶基或苯基脲及其类似物，它们是选择性的人类P2Y1受体抑制剂。本发明还提供了各种该类药物组成物和调节P2Y1受体活性以治疗对其反应的疾病的方法。
• Convergent and streamlined synthesis of 6-etherified imidazo[1,2-b]pyridazine-2-amine derivatives possessing VEGFR-2 kinase inhibitory activity
  作者：Kazuhisa Ishimoto、Yasuhiro Sawai、Naohiro Fukuda、Toshiaki Nagata、Tomomi Ikemoto

  DOI：10.1016/j.tet.2013.07.087

  日期：2013.10

  A convergent and streamlined synthesis of selective vascular endothelial growth factor receptor (VEGFR) 2 kinase inhibitors has been achieved using a synthetic strategy based on an SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in the final step. For the synthesis of 6-chloroimidazo[1,2-b]pyridazine, a one-pot reaction using 3-amino-6-chloropyridazine, cyclopropanecarboxamide, and bromoacetyl bromide was developed. The phenols were easily prepared by chemoselective acylation of 3-aminophenols with pyrazole carboxylic acids, and an efficient and high-yielding synthesis of N-ethylpyrazole was also developed. The SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in DMSO in the presence of cesium carbonate successfully proceeded at 100-110 degrees C to give the target products in good yields. This new chromatography-free process will be not only useful for the further bulk supply of these compounds but also applicable to the synthesis of other compounds containing the 6-etherified imidazo[1,2-b]pyridazin-2-amine core. (C) 2013 Elsevier Ltd. All rights reserved.
• BENZODIAZEPINE DERIVATIVES FOR TREATING A RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION
  申请人：Reviral Limited

  公开号：EP4048665A1

  公开（公告）日：2022-08-31
• US7674828B2
  申请人：——

  公开号：US7674828B2

  公开（公告）日：2010-03-09