3-(4-fluorophenyl)-4-(4-pyridyl)-1-(1-pyrrolidinomethyl)pyrazole | 311779-41-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(4-fluorophenyl)-4-(4-pyridyl)-1-(1-pyrrolidinomethyl)pyrazole
• 英文别名: 4-[3-(4-Fluorophenyl)-1-(pyrrolidin-1-ylmethyl)pyrazol-4-yl]pyridine
• CAS: 311779-41-6
• 化学式: C₁₉H₁₉FN₄
• 分子量: 322.385
• InChiKey: NVTYCOOJZHPRLX-UHFFFAOYSA-N

物化性质

• 沸点：
  438.4±45.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  34
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenyl)-4-(4-pyridyl)-1-(1-pyrrolidinomethyl)pyrazole 在 sodium hypochlorite 、 正丁基锂 、 2,2,6,6-四甲基哌啶氧化物 、 碳酸氢钠 、 potassium bromide 作用下， 以 四氢呋喃 、 正己烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 1.67h， 生成 3-(4-fluorophenyl)-1-methyl-5-(3-phenylpropyl)-4-(4-pyridyl)-pyrazole
  参考文献：
  名称：

  SUBSTITUTED PYRAZOLE COMPOUNDS

  摘要：

  公开号：

  EP1188754B1
• 作为产物：
  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

文献信息

• 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。
• US6667325B1
  申请人：——

  公开号：US6667325B1

  公开（公告）日：2003-12-23
• US7087624B2
  申请人：——

  公开号：US7087624B2

  公开（公告）日：2006-08-08
• 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
  作者：Koichi Hasumi、Shuichiro Sato、Takahisa Saito、Jun-ya Kato、Kazuhiko Shirota、Jun Sato、Hiroyuki Suzuki、Shuji Ohta

  DOI：10.1016/j.bmc.2014.05.045

  日期：2014.8

  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.
• SUBSTITUTED PYRAZOLE COMPOUNDS
  申请人：Teikoku Hormone Mfg. Co., Ltd.

  公开号：EP1188754B1

  公开（公告）日：2005-06-01