ethyl 1-(3-bromophenyl)-3-methyl-pyrazol-5-yl carboxylate | 209958-55-4

• 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-(3-bromophenyl)-3-methyl-pyrazol-5-yl carboxylate
• 英文别名: Ethyl 1-(3-bromophenyl)-3-methyl-1h-pyrazole-5-carboxylate；ethyl 2-(3-bromophenyl)-5-methylpyrazole-3-carboxylate
• CAS: 209958-55-4
• 化学式: C₁₃H₁₃BrN₂O₂
• 分子量: 309.162
• InChiKey: NDBUCFLWLTZNDG-UHFFFAOYSA-N

物化性质

• 沸点：
  400.3±35.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 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-(3-bromophenyl)-3-methyl-pyrazol-5-yl carboxylate 在 CuCN 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 ethyl-1-(3-cyanophenyl)-3-methyl-pyrazol-5-yl-carboxylate
  参考文献：
  名称：

  Nitrogen containing heteroaromatics as factor Xa inhibitors

  摘要：

  本申请描述了具有以下式I的含氮杂芳烃及其衍生物：##STR1##或其药用可接受的盐或前药形式，其中J为N或NH，D可以是C(.dbd.NH)NH.sub.2，这些化合物可用作因子Xa的抑制剂。

  公开号：

  US06020357A1
• 作为产物：
  描述：

  3-溴苯肼 、 2-(甲氧基亚胺)-4-氧代-戊酸乙酯 以 乙醇 为溶剂， 反应 5.0h， 生成 ethyl 1-(3-bromophenyl)-3-methyl-pyrazol-5-yl carboxylate
  参考文献：
  名称：

  Structure-Based Design of Novel Guanidine/Benzamidine Mimics:  Potent and Orally Bioavailable Factor Xa Inhibitors as Novel Anticoagulants

  摘要：

  As part of an ongoing effort to prepare orally active factor Xa inhibitors using structure-based drug design techniques and molecular recognition principles, a systematic study has been performed on the pharmacokinetic profile resulting from replacing the benzamidine in the P1 position with less basic benzamidine mimics or neutral residues. It is demonstrated that lowering the pK(a) of the P1 ligand resulted in compounds (3-benzylamine, 15a; 1-aminoisoquinoline, 24a; 3-aminobenzisoxazole, 23a; 3-phenylcarboxamide, 22b; and 4-methoxyphenyl, 22a) with improved pharmacokinetic features mainly as a result of decreased clearance, increased volume of distribution, and enhanced oral absorption. This work resulted in a series of potent and orally bioavailable factor Xa inhibitors that ultimately led to the discovery of SQ311, 24a. SQ311, which utilizes a 1-aminoisoquinoline as the P1 ligand, inhibits factor Xa with a K-i of 0.33 nM and demonstrates both good in vivo antithrombotic efficacy and oral bioavailability.

  DOI：

  10.1021/jm020578e

文献信息

• Synthesis and Insecticidal Evaluation of Aryl Pyrazole 5-Fluorouracil Compounds
  作者：Yue Chen、Xiao-Dong Fu、Hai-Ping Mu、Xiao-Fei Qin、Rong Wan

  DOI：10.3184/174751914x13955977912102

  日期：2014.5

  Twenty eight aryl pyrazole derivatives containing 5-fluorouracil were designed and synthesised via the key intermediate 1-aryl-3-methyl-1 H-pyrazole-5-carboxylic acid. The structures of target compounds were confirmed by ¹H NMR, FT-IR, EA and their insecticidal activities were evaluated. The bioassays revealed that aryl pyrazole derivatives containing 5-fluorouracil exhibited excellent insecticidal activities against Culex pipiens and Musca domestica at a concentration of 0.1%. Some compounds still showed good insecticidal activities even at a concentration of 0.05%.

  通过关键中间体 1-芳基-3-甲基-1 H-吡唑-5-羧酸，设计并合成了含有 5-氟尿嘧啶的 28 种芳基吡唑衍生物。通过 1H NMR、FT-IR 和 EA 确认了目标化合物的结构，并评估了它们的杀虫活性。生物测定结果表明，含有 5-氟尿嘧啶的芳基吡唑衍生物在 0.1% 的浓度下对喙库蚊和家蝇具有极佳的杀虫活性。一些化合物即使在 0.05% 的浓度下仍表现出良好的杀虫活性。
• Substituted biaryl pyrazoles as sodium channel blockers
  作者：Sriram Tyagarajan、Prasun K. Chakravarty、Bishan Zhou、Brett Taylor、Michael H. Fisher、Mathew J. Wyvratt、Kathy Lyons、Tracy Klatt、Xiaohua Li、Sanjeev Kumar、Brande Williams、John Felix、Birgit T. Priest、Richard M. Brochu、Vivien Warren、McHardy Smith、Maria Garcia、Gregory J. Kaczorowski、William J. Martin、Catherine Abbadie、Erin McGowan、Nina Jochnowitz、William H. Parsons

  DOI：10.1016/j.bmcl.2010.07.080

  日期：2010.9

  Voltage-gated sodium channels have been shown to play a critical role in neuropathic pain. A series of low molecular weight biaryl substituted pyrazole carboxamides were identified with good in-vitro potency and in-vivo efficacy. Compound 26, a Nav1.7 blocker has excellent efficacy in the Chung model of neuropathic pain.

  电压门控钠通道已显示在神经性疼痛中起关键作用。鉴定出一系列具有良好的体外效能和体内功效的低分子量联芳基取代的吡唑甲酰胺。化合物26（Na v 1.7阻滞剂）在神经性疼痛的Chung模型中具有出色的疗效。
• [EN] NITROGEN CONTAINING HETEROAROMATICS AS FACTOR Xa INHIBITORS<br/>[FR] COMPOSES HETEROAROMATIQUES CONTENANT DE L'AZOTE, UTILISES EN TANT QU'INHIBITEURS DU FACTEUR Xa
  申请人：DU PONT PHARMACEUTICALS COMPANY

  公开号：WO1998028269A1

  公开（公告）日：1998-07-02

  (EN) The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula (I) or pharmaceutically acceptable salt or prodrug forms thereof, wherein J is N or NH and D may be C(=NH)NH2, which are useful as inhibitors of factor Xa.(FR) La présente invention se rapporte à des composés hétéroaromatiques contenant de l'azote et à des dérivés de tels composés représentés par la formule (I), ou à des sels ou bioprécurseurs pharmaceutiquement acceptables de ces composés utiles en tant qu'inhibiteurs du facteur Xa. Dans la formule (I), J est N ou NH et D peut être C(=NH)NH2.

  (中) 本申请描述了含氮杂环芳香族化合物及其衍生物的公式(I)，或其药学上可接受的盐或前药形式，其中J为N或NH，D可能是C(=NH)NH2，这些化合物可用作凝血因子Xa的抑制剂。
• [EN] CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF<br/>[FR] MODULATEURS DE CALPAIN ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：BLADE THERAPEUTICS INC

  公开号：WO2018064119A8

  公开（公告）日：2019-04-25
• NITROGEN CONTAINING HETEROAROMATICS AS FACTOR Xa INHIBITORS
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP0946508B1

  公开（公告）日：2009-09-23