1-(2-cyanoethyl)-5-(3,5-difluorophenyl)-3-formyl-4-methyl-1H-pyrazole | 932706-53-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-cyanoethyl)-5-(3,5-difluorophenyl)-3-formyl-4-methyl-1H-pyrazole
• 英文别名: 3-[5-(3,5-Difluorophenyl)-3-formyl-4-methylpyrazol-1-yl]propanenitrile；3-[5-(3,5-difluorophenyl)-3-formyl-4-methylpyrazol-1-yl]propanenitrile
• CAS: 932706-53-1
• 化学式: C₁₄H₁₁F₂N₃O
• 分子量: 275.258
• InChiKey: XXBFRRQLFFDOTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  58.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-cyanoethyl)-5-(3,5-difluorophenyl)-3-formyl-4-methyl-1H-pyrazole 、 (1S,3R)-3-fluorocyclopentanamine 在 Zn(BH3CN)2 作用下， 以 甲醇 为溶剂， 以85%的产率得到3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}-methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile
  参考文献：
  名称：

  Identification of MK-1925: A selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist

  摘要：

  Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. The compound also showed in vivo efficacy after oral dosing. Therefore, compound 39 was selected to undergo further studies as a clinical candidate. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.051
• 作为产物：
  描述：

  3-(5-(3,5-difluorophenyl)-3-(hydroxymethyl)-4-methyl-1H-pyrazol-1-yl)propanenitrile 在 戴斯-马丁氧化剂 作用下， 以 氯仿 为溶剂， 以75%的产率得到1-(2-cyanoethyl)-5-(3,5-difluorophenyl)-3-formyl-4-methyl-1H-pyrazole
  参考文献：
  名称：

  Identification of MK-1925: A selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist

  摘要：

  Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. The compound also showed in vivo efficacy after oral dosing. Therefore, compound 39 was selected to undergo further studies as a clinical candidate. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.051

文献信息

• Aryl-Substituted Nitrogen-Containing Heterocyclic Compounds
  申请人：Ito Hirokatsu

  公开号：US20090275617A1

  公开（公告）日：2009-11-05

  Disclosed is an aryl-substituted nitrogen-containing heterocyclic compound represented by the formula (I) below or a pharmaceutically acceptable salt thereof. This compound serves as nociceptin receptor antagonist and is useful as a pharmaceutical agent for treating diseases associated with a nociceptin receptor. (I) [in the formula, A 1 , A 2 and A 3 independently represent a carbon atom or a nitrogen atom, and one or two of A 1 , A 2 and A 3 represent a carbon atom; R 1 represents a lower alkyl group or the like; R 2 represents a phenyl group which may be substituted with a halogen atom or the like; R 3 represents a hydrogen atom, a lower alkyl group or the like; and R 4 represents a lower alkyl group or the like.]

  本发明公开了一种芳基取代的含氮杂环化合物，其化学式如下（I），或其药学上可接受的盐。该化合物作为伤害感受受体拮抗剂，并且可用作治疗与伤害感受受体相关的疾病的药物。 （I）[在该式中，A1，A2和A3独立地表示碳原子或氮原子，其中一个或两个A1，A2和A3表示碳原子；R1表示较低的烷基或类似物；R2表示苯基，其可以用卤素原子或类似物取代；R3表示氢原子，较低的烷基或类似物；R4表示较低的烷基或类似物。]
• ARYL-SUBSTITUTED NITROGEN-CONTAINING HETEROCYCLIC COMPOUND
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1935881A1

  公开（公告）日：2008-06-25

  Disclosed is an aryl-substituted nitrogen-containing heterocyclic compound represented by the formula (I) below or a pharmaceutically acceptable salt thereof. This compound serves as nociceptin receptor antagonist and is useful as a pharmaceutical agent for treating diseases associated with a nociceptin receptor. (I) [in the formula, A1, A2 and A3 independently represent a carbon atom or a nitrogen atom, and one or two of A1, A2 and A3 represent a carbon atom; R1 represents a lower alkyl group or the like; R2 represents a phenyl group which may be substituted with a halogen atom or the like; R3 represents a hydrogen atom, a lower alkyl group or the like; and R4 represents a lower alkyl group or the like.]

  本发明公开了由下式(I)代表的芳基取代的含氮杂环化合物或其药学上可接受的盐。该化合物可作为痛觉素受体拮抗剂，可用于治疗与痛觉素受体相关的疾病。(I) [式中，A1、A2 和 A3 分别代表碳原子或氮原子，A1、A2 和 A3 中的一个或两个代表碳原子；R1 代表低级烷基或类似基团；R2 代表可被卤素原子或类似基团取代的苯基；R3 代表氢原子、低级烷基或类似基团；R4 代表低级烷基或类似基团。］
• US7829586B2
  申请人：——

  公开号：US7829586B2

  公开（公告）日：2010-11-09
• Identification of MK-1925: A selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist
  作者：Kensuke Kobayashi、Tomohiro Tsujita、Hirokatsu Ito、Satoshi Ozaki、Takeshi Tani、Yasuyuki Ishii、Shoki Okuda、Kiyoshi Tadano、Takahiro Fukuroda、Hisashi Ohta、Osamu Okamoto

  DOI：10.1016/j.bmcl.2009.06.051

  日期：2009.8

  Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-([(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. The compound also showed in vivo efficacy after oral dosing. Therefore, compound 39 was selected to undergo further studies as a clinical candidate. (C) 2009 Elsevier Ltd. All rights reserved.