4-Nitro-2-[2-(oxan-2-yloxy)ethyl]-5-pentan-3-ylpyrazole-3-carboxylic acid | 1436852-36-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-Nitro-2-[2-(oxan-2-yloxy)ethyl]-5-pentan-3-ylpyrazole-3-carboxylic acid
• 英文别名: 4-nitro-2-[2-(oxan-2-yloxy)ethyl]-5-pentan-3-ylpyrazole-3-carboxylic acid
• CAS: 1436852-36-6
• 化学式: C₁₆H₂₅N₃O₆
• 分子量: 355.391
• InChiKey: YGGFTQQDCADWBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-Nitro-2-[2-(oxan-2-yloxy)ethyl]-5-pentan-3-ylpyrazole-3-carboxylic acid 、 2-氨基苯乙酮盐酸盐 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以76%的产率得到4-nitro-2-[2-(oxan-2-yloxy)ethyl]-5-pentan-3-yl-N-phenacylpyrazole-3-carboxamide
  参考文献：
  名称：

  Discovery of potent, selective, bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model, Part I: Transformation of selective pyrazolodiazepinone phosphodiesterase 4 (PDE4) inhibitors into selective PDE2 inhibitors

  摘要：

  We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of PDE4 inhibitors, while simultaneously minimizing PDE4 activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like mode in contrast to the cAMP-like binding mode found in PDE4. Structure activity relationship studies coupled with an inhibitor bound crystal structure in the active site of the catalytic domain of PDE2 identified structural features required to minimize PDE4 inhibition while simultaneously maximizing PDE2 inhibition. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.072
• 作为产物：
  描述：

  3-乙基-2-戊酮 在 偶氮二甲酸二异丙酯 、 水 、 sodium ethanolate 、 copper(II) nitrate 、 一水合肼 、 三氟乙酸酐 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 氯仿 为溶剂， 生成 4-Nitro-2-[2-(oxan-2-yloxy)ethyl]-5-pentan-3-ylpyrazole-3-carboxylic acid
  参考文献：
  名称：

  Discovery of potent, selective, bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model, Part I: Transformation of selective pyrazolodiazepinone phosphodiesterase 4 (PDE4) inhibitors into selective PDE2 inhibitors

  摘要：

  We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of PDE4 inhibitors, while simultaneously minimizing PDE4 activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like mode in contrast to the cAMP-like binding mode found in PDE4. Structure activity relationship studies coupled with an inhibitor bound crystal structure in the active site of the catalytic domain of PDE2 identified structural features required to minimize PDE4 inhibition while simultaneously maximizing PDE2 inhibition. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.072

文献信息

• Discovery of potent, selective, bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model, Part I: Transformation of selective pyrazolodiazepinone phosphodiesterase 4 (PDE4) inhibitors into selective PDE2 inhibitors
  作者：Mark S. Plummer、Joseph Cornicelli、Howard Roark、Donald J. Skalitzky、Charles J. Stankovic、Susan Bove、Jayvardhan Pandit、Annise Goodman、James Hicks、Aurash Shahripour、David Beidler、Xiao Kang Lu、Brian Sanchez、Christopher Whitehead、Ron Sarver、Timothy Braden、Richard Gowan、Xi Qiang Shen、Katherine Welch、Adam Ogden、Nalini Sadagopan、Heidi Baum、Howard Miller、Craig Banotai、Cindy Spessard、Sandra Lightle

  DOI：10.1016/j.bmcl.2013.03.072

  日期：2013.6

  We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of PDE4 inhibitors, while simultaneously minimizing PDE4 activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like mode in contrast to the cAMP-like binding mode found in PDE4. Structure activity relationship studies coupled with an inhibitor bound crystal structure in the active site of the catalytic domain of PDE2 identified structural features required to minimize PDE4 inhibition while simultaneously maximizing PDE2 inhibition. (C) 2013 Elsevier Ltd. All rights reserved.