3-dimethylamino-1-(4-fluorophenyl)-2-(4-pyridyl)-2-propen-1-one | 148671-39-0

• 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: 3-dimethylamino-1-(4-fluorophenyl)-2-(4-pyridyl)-2-propen-1-one
• 英文别名: 3-dimethylamino-1-(4-fluorophenyl)-2-(pyridin-4-yl)-2-propen-1-one；3-(dimethylamino)-1-(4-fluorophenyl)-2-(4-pyridyl)prop-2-en-1-one；3-(Dimethylamino)-1-(4-fluorophenyl)-2-(pyridin-4-yl)prop-2-en-1-one；3-(dimethylamino)-1-(4-fluorophenyl)-2-pyridin-4-ylprop-2-en-1-one
• CAS: 148671-39-0
• 化学式: C₁₆H₁₅FN₂O
• 分子量: 270.306
• InChiKey: YOIDNBKTAAGZJE-UHFFFAOYSA-N

物化性质

• 沸点：
  411.1±45.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-dimethylamino-1-(4-fluorophenyl)-2-(4-pyridyl)-2-propen-1-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 7.0h， 生成 3-(4-fluorophenyl)-4-(4-pyridyl)-1-(1-pyrrolidinomethyl)pyrazole
  参考文献：
  名称：

  Design and synthesis of 5-[(2-chloro-6-fluorophenyl)acetylamino]-3-(4-fluorophenyl)-4-(4-pyrimidinyl)isoxazole (AKP-001), a novel inhibitor of p38 MAP kinase with reduced side effects based on the antedrug concept

  摘要：

  Inhibitors of p38 mitogen-activated protein (MAP) kinase, which are closely involved in the production of inflammatory cytokines, are considered promising curative drugs for chronic inflammatory disorders. However, there is also a growing concern regarding its systemic side effects. To reduce the occurrence of side effects, we have identified a novel p38 MAP kinase inhibitor that shows properties of an antedrug, which imparts its effect solely on the inflammatory site and is metabolically inactivated right after. We have designed isoxazole derivatives through the addition of a fresh interacting fourth site to the structure of the prototypical p38 MAP kinase inhibitor that harbors three point interactive sites. The derivative 26d (AKP-001) shows excellent p38 MAP kinase inhibitory activity and a high selectivity for various kinases. Its rapid metabolism has been confirmed in rats. Moreover, 26d has been shown to be effective in animal models of inflammatory bowel disease.

  DOI：

  10.1016/j.bmc.2014.05.045
• 作为产物：
  描述：

  1-(4-氟苯基)-2-(4-吡啶基)乙酮 、 N,N-二甲基甲酰胺二甲基缩醛 在 氮气 、 异丙醚 作用下， 反应 3.0h， 以to yield 3-dimethylamino-1-(4-fluorophenyl)-2-(pyridin-4-yl)-2-propen-1-one (6.15 g)的产率得到3-dimethylamino-1-(4-fluorophenyl)-2-(4-pyridyl)-2-propen-1-one
  参考文献：
  名称：

  Pyrazole derivatives

  摘要：

  新的杂环衍生物的公式为：##STR1## 其中R.sup.1是芳基，可以具有合适的取代基或杂环基，可以具有合适的取代基，R.sup.2是芳基，可以具有合适的取代基或杂环基，可以具有合适的取代基，R.sup.3是氢或酰基，R.sup.4是氢，低烷基，环（低）烷基，环（低）烷基-（低）烷基，羧基（低）烷基，受保护的羧基（低）烷基，芳基（低）烷基，可以具有合适的取代基，芳基（低）烯基，桥联三环烷基，可以具有合适的取代基的杂环基，酰基或公式##STR2##（其中A是低烷基），R.sup.5是氢或低烷基的制药上可接受的盐，它们可用作药物。

  公开号：

  US05670503A1

文献信息

• [EN] PYRAZOLOPYRIDINE DERIVATES<br/>[FR] DERIVES DE PYRAZOLOPYRIDINE
  申请人：URIACH Y COMPANIA S A J

  公开号：WO2004076450A1

  公开（公告）日：2004-09-10

  New compounds of formula (I) and the salts, solvates and prodrugs thereof, wherein the meanings for the various substituents are as disclosed in the description. These compounds are useful as p38 kinase inhibitors.

  公式（I）的新化合物及其盐、溶剂合物和前药，其中各种取代基的含义如描述中所披露的。这些化合物可用作p38激酶抑制剂。
• Substituted pyrazole compounds
  申请人：Teikoku Hormone Mfg. Co., Ltd.

  公开号：US06667325B1

  公开（公告）日：2003-12-23

  Substituted pyrazole compounds represented by formula (I), or salts thereof are disclosed, wherein R1 is —CH(OH)—CH(R4)—(A)n—Y, —CH2—CH(R4)—(A)n—Y, —CO—B1—A—Y or the like (wherein A is a lower alkylene; Y is an aryl group which may be substituted, for example, by halogen, or the like; R4 is a hydrogen atom or a lower alkyl group; B1 is —CH(R4)— or —N(R4)—; and n is 0 or 1); R2 is a hydrogen atom, a lower alkyl group which may be substituted by hydroxyl or the like, or an aralkyl group; R3 is a phenyl group which may be substituted by halogen or the like, or a pyridyl group; and Q is a pyridyl or quinolyl group. These substituted pyrazole compounds or their salts have an excellent p38MAP kinase inhibiting effect and are hence useful in the prevention or treatment of tumor necrosis factor &agr;-related diseases, interleukin 1-related diseases, interleukin 6-related diseases or cyclooxygenase II-related diseases.

  本发明公开了由式(I)表示的取代吡唑化合物或其盐，其中R1为—CH(OH)—CH(R4)—(A)n—Y，—CH2—CH(R4)—(A)n—Y，—CO—B1—A—Y或类似物（其中A为较低的烷基；Y为芳基，可以被卤素等取代；R4为氢原子或较低烷基基团；B1为—CH(R4)—或—N(R4)—；n为0或1）；R2为氢原子，可以被羟基等取代的较低烷基基团，或芳基烷基基团；R3为可以被卤素等取代的苯基或吡啶基；Q为吡啶基或喹啉基。这些取代的吡唑化合物或其盐具有优异的p38MAP激酶抑制作用，因此在预防或治疗肿瘤坏死因子α相关疾病、白细胞介素1相关疾病、白细胞介素6相关疾病或环氧合酶II相关疾病方面非常有用。
• Ligand–Protein Interactions of Selective Casein Kinase 1δ Inhibitors
  作者：Scot Mente、Eric Arnold、Todd Butler、Subramanyam Chakrapani、Ramalakshmi Chandrasekaran、Kevin Cherry、Ken DiRico、Angela Doran、Katherine Fisher、Paul Galatsis、Michael Green、Matthew Hayward、John Humphrey、John Knafels、Jianke Li、Shenping Liu、Michael Marconi、Scott McDonald、Jeff Ohren、Vanessa Paradis、Blossom Sneed、Kevin Walton、Travis Wager

  DOI：10.1021/jm4006324

  日期：2013.9.12

  differences in the hinge region between CK1δ and p38 to find selective inhibitors that have minimal p38 activity. The SAR, brain exposure, and the effect of these inhibitors on mouse circadian rhythms are described. The in vivo evaluation of these inhibitors demonstrates that selective inhibition of CK1δ at sufficient central exposure levels is capable of modulating circadian rhythms.

  酪蛋白激酶1δ（CK1δ）和1ε（CK1ε）被认为是调节所有哺乳动物昼夜节律的必需酶。在我们先前发表的证明CK1ε优先化合物是无效的昼夜节律调节剂的工作的基础上，我们合成了一系列对CK1δ亚型具有选择性的吡唑取代的吡啶抑制剂。此外，使用基于结构的药物设计，我们已经能够利用CK1δ和p38之间铰链区的差异来发现具有最小p38活性的选择性抑制剂。描述了SAR，大脑暴露以及这些抑制剂对小鼠昼夜节律的影响。这些抑制剂的体内评估表明，在足够的中枢暴露水平下对CK1δ的选择性抑制能够调节昼夜节律。
• Pyrazolopyridine derivates
  申请人：Almansa Rosales Carmen

  公开号：US20060167040A1

  公开（公告）日：2006-07-27

  New compounds of formula (I) and the salts, solvates and prodrugs thereof, wherein the meanings for the various substituents are as disclosed in the description. These compounds are useful as p38 kinase inhibitors.

  新化合物的公式为（I），以及其盐，溶剂合物和前药，其中各种取代基的含义如描述所示。这些化合物可用作p38激酶抑制剂。
• Pyrazole derivatives
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05624931A1

  公开（公告）日：1997-04-29

  Pyrazole derivatives useful for inhibiting the production of Interleukin-1 (IL-1) and tumor necrosis factor (TNF) and the like, which can be represented by the following formula: ##STR1## and a pharmaceutical composition containing the same and to uses thereof.

  吡唑类衍生物可用于抑制白细胞介素-1（IL-1）和肿瘤坏死因子（TNF）等的产生，其可由以下公式表示：##STR1##以及含有其的制药组合物和用途。